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PHPY303
midterm #1
289
Physiology
Undergraduate 3
02/05/2013

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Term
Describe the mechanism of action for FSH and LH at the testes
Definition
G-protein receptor cascade, initiating adenylyl cyclase pathway.
Adenylyl cyclase increases cAMP, which activates PKA which then leads to the transcription/translation
Term
True or false:
ABP, aromatase, growth factors and inhibin are all produced in leydig through the control of luteinizing hormone.
Definition
False.
It is FSH, follicle stimulating hormone, which binds to sertoli cells and initiates the production of those proteins.
Term
Inhibin works through a negative feedback mechanism to inhibit what?
Definition
To inhibit the anterior pituitary from producing FSH.
Term
Androgens work through negative feedback mechanisms to inhibit what?
Definition
1) The hypothalamus (testosterone stops it from releasing GnRH)
2) The anterior pituitary (testosterone causes it to stop producing LH)
Term
Which hormones are the primary regulators of testicular function?
Definition
FSH and LH.
Term
Human chorionic gonadotropin (hCG)
Definition
Begins being produced in the first few weeks of pregnancy and is what is detected by pregnancy tests for a positive result.
Term
Which important hormones belong to the glycoprotein family of hormones? What's the same and what's different about them?
Definition
LH, FSH, hCG (human chorionic gonadotropin), TSH (thyroid stimulating hormone)
Each is composed of alpha and beta sub units. The alpha sub units, however, are the same (between FSH/LH and hCG/TSH) whereas it is the beta sub units that that differ and confer the different functional/immunological characteristics.
Term
What other molecule has actions that are similar to those of LH.
Definition
hCG (human chorionic gonadotropin)
Term
True or false:
LH production is greater than that of FSH production before puberty, but after puberty the proportions reverse (with FSH then being produced at higher concentrations.
Definition
FALSE.
FSH production is greater than that for LH before puberty, with the proportions reversing after puberty. This is due to GnRH preferentially triggering LH release in males.
Term
How does LH act, describe its mechanism of action?
Definition
Adenylyl cyclase, increase cAMP, PKA, PKA diffuses into the cell membrane to the cell nucleus, causes the transcription/translation of SCP and SAP and the other ones which are found to enhance the process of testosterone formation.
SCP ==> sterol-carrier protein
SAP ==> sterol-activating protein
Term
what is responsible for carrying the different characteristics which we must inherit during the process of fertilization?
Definition
Chromosomes
Term
Karyotype
Definition
Refers to the total number of chromosomes in a cell
Term
Autosomes
Definition
Chromosomes which do not encode sex characteristics

In the human karyotype there are 23 pairs of chromosomes, 22 of which are autosomal chromosomes (Ie chromosomes that do NOT encode sex characteristics) and 1 is a sex chromosome.
Term
What's the difference between male and female sex chromosomes?
Definition
Females: XX
Males: XY
Note: The male sex chromosome is small and acrocentric (The centromere is located at the end of the chromosome)

THEREFORE: Women have 8 pairs of chromosomes whereas men have 7 1/2
Term
Acrocentric
Definition
Refers to a chromosome (Ie the Y chromosome) where the centromere is located at the end of the chromosome.
Term
Mitosis
Definition
Non-reproductive process of cellular division in somatic cells.
Key in growth.
Results in two daughter cells that have the same chromosomal number and identical DNA content.

5 phases:
Prophase --> prometaphase --> metaphase --> anaphase --> telophase
Term
What are the phases of mitosis
Definition
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
Term
Describe the steps of mitosis
Definition
Prophase --> chromosomes double to 92
Prometaphase --> nucleus dissolves / microtubules attach to centromere
Metaphase --> chromosomes align @ the middle of the cell
Anaphase --> Separated chromosomes pull apart
Telophase --> microtubules disappear and cell division begins
Cytokinesis --> splitting apart the cells (entering into 'interphase')
Term
True or false:
Leydig cells secrete AMH
Definition
False.
Leydig cells secrete testosterone.
sertoli cells secrete AMH.
Term
Which cells secrete testosterone?
Definition
Leydig cells
Term
Which cells secrete AMH?
Definition
sertoli cells
Term
What are sertoli cells and what do they secrete?
Definition
cells of the testes that secrete AMH as well as ABP (androgen binding protein)
Term
what are leydig cells and what do they secrete?
Definition
cells of the testes that secrete testosterone.
Term
True or false:
The testes are a requirement for the development of male characteristics just as the ovaries are a requirement for the development of female characteristics.
Definition
false.
while it is true that the testes are needed for the production of testosterone, the ovaries can be removed without any adverse issues with it still developing into female genitalia.
Term
in a scenario where a boy has testosterone, but the testosterone receptors in his body have a low affinity for testosterone, would we expect the boy to have undergone feminization?
Definition
not necessarily. However, if there's a reduced affinity for testosterone then there will be a reduced occurrence in the cascades of reactions that testosterone is responsible (the ones that activate SRE (steroid response element) that give men their male characteristics) and therefore while he may not undergo feminization he will likely have underdeveloped male characteristics.
Term
what is SRE and what does it do?
Definition
SRE refers to "steroid response element" which is a section of DNA that triggers the transcriptional regulation for the production of a series of proteins with specific functions - among those functions being the development of male secondary characteristics.
Term
If you were to castrate a female fetus @ 8 weeks of development, how would we expect its genitals to form?
Definition
The mullerian ducts continue to develop along the female pathway.

the ovaries are not necessary for the development of female genitalia… so the development of the fallopian tubes and the uterus does not require the presence of the ovaries.
Term
what does the early increase in Leydig cells and secretion of testosterone depend on?
Definition
maternal chorionic gonadotropin (hCG)
fetal luteinizing hormone (LH)
Term
where do spermatozoa form?
Definition
within the seminiferous tubules.
Term
the seminiferous tubules are formed from what type of tissue type?
Definition
from sertoli cells, interspersed with germ cells.
Term
true or false:
mature germ cells are typically found around the periphery of the seminiferous tubules.
Definition
false, the mature germ cells are typically found near the lumen of the tubule.
*the leydig cells are interstitial cells that lay in between the tubules … they produce testosterone.
Term
how many spermatids are produced from one spermatogonia
Definition
4
Term
true or false:
the "luteneizing surge" at the beginning of life has serious detrimental effects on the baby.
Definition
true or false:
the "luteneizing surge" at the beginning of life has serious detrimental effects on the baby.
Term
true or false: the hypothalamus produces steroid hormones
Definition
false. it produces inhibitory or excitatory peptide hormones.
example: corticotropin releasing hormone (etc)
Term
True or false: the hypothalamus produces peptide hormones
Definition
True. It produces inhibitory and excitatory peptide hormones.
Term
Neurohypophysis
Definition
The posterior pituitary gland (axon terminations)
Term
Adenohypophysis
Definition
The anterior pituitary gland (composed of several types of cells x-tropic cells)
Term
True or false:
Oxytocin and ADH (vasopressin) are produced in the posterior pituitary.
Definition
False.
They are produced in the paraventricular nucleus of the hypothalamus.
They are released from the posterior pituitary.
Term
Retrograde emission
Definition
Occurs when the internal urethra sphincter fails to constrict, leading to retrograde movement of sperm into the urinary bladder.

Can result from any process that interferes with the innervation of the vas deferens and bladder neck. (diabetes mellitis and peripheral neuropathy… MS or medications)
It may, therefore, occur as a result of nerve damage.
Term
What is the treatment for ejaculatory dysfunction?
Definition
So long as the cause was not surgical in nature, you can typically treat it pharmaceutically with 'sympathomimetic drugs' that promote normal ejaculation by increasing the tone of the as deferens and the internal sphincter.
Term
Increased tone of the vas deferens would result in what?
Definition
Increased propelling force of semen through the vas deferens.
Term
Strengthening of the internal urethral sphincter would result in what?
Definition
Reduction in retrograde emission.
Term
Where is progesterone produced?
Definition
The corpus luteum
Term
Describe the structure of the ovary.
Definition
Inner medulla, outer zone (or cortex) that surrounds the medulla but not the hilus (the area through which blood vessels/lymphatics/nerves enter the ovary)
Term
What are the basic stages of the ovarian cycle?
Definition
Folliculogenesis, ovulation, formation of the corpus luteum.
Term
Folliculogenesis
Definition
In females, follicles mature in stages from primordial to graafian (or preovulatory) follicles.
Term
Describe the levels of gonadotropins in a female throughout her life.
Definition
Gonadotropins = LH and FSH.
Peaks first during fetal life and again during early infancy, before falling to low levels throughout the rest of childhood. (high FSH, low LH)
@ onset of puberty the levels of both begin to rise and then begin to oscillate at regular monthly intervals. (low FSH, high LH)
@ menopause they rise to very high levels.
Term
"menopause" in both females and males is due to what?
Definition
Due to a loss of receptor sensitivity. While hormones (gonadotropins) are still being produced they are no longer binding to receptors with any affinity.
Term
The pulsatile release of gonadotropins is one what type of time scale?
Definition
Hourly.
That is how often there is a surge in GnRH
Term
Where is the pulse generator for GnRH found?
Definition
In the acruate nucleus of the hypothalamus.
Term
Does an individuals sensitivity to gonadotropins remain constant throughout their lifetime?
Definition
No.
When you're an infant your
Term
Which cells specifically do FSH and LH target?
Definition
FSH -
Sertoli cells (in males)
Granulosa cells (in females)

LH -
Leydig cells (in males)
Theca cells (in females)

cAMP pathway.
Term
The pulsatile release of GnRH is responsible for what monthly cycle?
Definition
The menstrual cycle in females.
Term
The hypothalamic-pituitary-gonadal axis is responsible for
a) Circadian rhythm
b) Menstrual cycle
c) Ovarian cycle
d) Orreahn cycle
Definition
B - menstrual cycle
Term
Describe the negative feedback of estrogen on gonadotropin release
Definition
Feedback is tied to changes at the level of the receptors and different phases of life.

During infancy and childhood the negative feedback response is particularly sensitive to the [LH] [FSH] that are being produced.
This sensitivity decreases until adolescence, where it becomes low enough again to initiate the GnRH release mechanism - leading to larger amounts of estrogen being produced.
The sensitive continues to decrease onto adulthood wherein the levels of gonadotropins required to stimulate the negative feedback mechanism reach its peak.
Term
Why can you remove the ovaries from a developing female fetus with no adverse affects to its gender development but you cannot remove the testes from a male developing fetus without initiating the conversion into female characteristics?
Definition
because the development of male uro-genital ducts requires the presence of two hormones: AMH and testosterone.

this is not the case with ovaries, which contribute no hormonal regulation to the development of those ducts, and therefore when they're removed the girl can still undergo regular development.
Term
What would we expect with regards to uro-genital development if we were to unilaterally remove testes from a developing fetus of 8 weeks?
Definition
unilateral removal of the testis results in female duct development ipsilateral to the castration.
the duct develops in a male pattern on the side with the remaining testis and virilisation of the external genitalia proceeds normally.

(causes a form of hermaphrodite)
Term
a developing male fetus has its testes removed before 9 weeks, but the scientists begin administering testosterone immediately. What would we expect from his development?
Definition
Development of male uro-genital ducts requires the presence of two hormones: testosterone and AMH.

If the patient is being treated with testosterone then we would expect the wolffian ducts to persist. However, because AMH is required to break down the mullerian ducts, the mullerian duct also persists.
Term
androgens refer to?
Definition
testosterone
dihydrotestosterone
Term
how do you produce dihydrotestosterone? What's special about it?
Definition
the enzyme 5−α−reductase converts testosterone into dihydrotestosterone.

dihydrotestosterone has a much higher affinity than testosterone (100x better) and so most of the work in the body that we may attribute to testosterone is actually dihydrotestosterone.

in males, if you lack 5−α−reductase then you will have a low concentration of DHT and then will develop female characteristics.
Term
Male pattern of sexual differentiation depends on what hormones? Where are they produced?
Definition
three hormones:
1) AMH
2) testosterone
3) dihydrotestosterone

AMH and testosterone are produced in the testes and are a requirement for the Wolffian phase of male development.

Dihydrotestosterone is produced in the peripheral tissues where testosterone is converted to DHT via 5−α−reductase . It is required for virilization of the urogenital sinus, the prostate, the penile urethra and the external genitalia during embryogenesis, as does sexual maturation at puberty.
Term
what is SRY?
Definition
sex-determining region Y.

is a single gene found on the short arm of the y-chromosome which triggers the development of the testis through its gene product "testis determining factor (TDF)"
Term
what is TDF?
Definition
TDF = testis determining factor.
it is contained within a portion of the short-arm of the y-chromosome called SRY or "sex-determining region Y"
Term
if TDF is not present or TDF becomes present after the first 9 weeks of fetal development, what would we expect for the development of a male fetus?
Definition
we would expect it to develop with female characteristics.
Term
what are androgens role(s) in the male phenotypic differentiation?
Definition
- trigger the conversion of wolffian ducts to the male ejaculatory system
- direct the differentiation of the urogenital sinus and external genitalia
Term
functions of DHT. Where is it produced. How is it produced?
Definition
Dihydrotestosterone is produced in the peripheral tissues where testosterone is converted to DHT via 5−α−reductase . It is required for virilization of the urogenital sinus, the prostate, the penile urethra and the external genitalia during embryogenesis, as does sexual maturation at puberty.
Term
which stage of male sexual differentiation is regulated by DHT?
Definition
the sexual maturation that occurs at puberty,
+ virilization of the urogenital sinus, the prostate, the penile urethra and the external genitalia during embryogenesis requires DHT
Term
which stage of sexual differentiation is regulated by testosterone?
Definition
the wolffian phase
Term
the male sexual differentiation can be broken down into stages. what are they?
Definition
the wolffian phase
sexual maturation
Term
True or false:
testosterone only begins being produced after the 9th week of fetal development.
Definition
false, it begins being produced even earlier than that.
Term
True or false:
testosterone begins being produced before AMH.
Definition
False.
After the formation of the testicular cords, the sertoli cells start producing AMH THEN the fetal leydig cells start producing testosterone.
Term
What is androgen binding protein?
Definition
it is a protein that is produced by the sertoli cells of the testis.

It's role is to bind to testosterone so as to maintain a high concentration locally to stimulate growth and differentiation of the wolffian ducts into the epididymis, the vas deferens, the seminal vesicles, the ejaculatory duct
-- as well as differentiation of the medulla of the gonad into the rete testes.
Term
true or false:
the internal male ducts respond to both DHT and testosterone.
Definition
False.
The cells of the wolffian duct lack the enzyme 5α−reductase and therefore cannot convert testosterone into DHT. So, they respond to testosterone (per se)
Term
which hormone is required for the normal male development of the external genitalia?
Definition
DHT
Term
True or false:
As we age, both males and females experience a decrease in testosterone serum levels and an increase in LH serum levels.
Definition
False. While they do experience a fall in testosterone levels they do not, infact, experience an increase in the LH levels.
This is because the androgen receptor affinity for testosterone falls as they age.
Term
When do the different spikes of testosterone occur during an individuals lifespan?
Definition
Between three and six months of fetal development (9 weeks),
During the first few months of life,
@ puberty, after which it plateaus until it begins to fall in old age.
Term
Where and how is testosterone metabolized?
Definition
Metabolized mainly in the liver and the prostate (very little {2%} excreted in urine)
Converted to 17-ketosteroids in the liver
Converted to DHT in the prostate
Term
Describe the functions of androgens.
Definition
1) Major roles in male phenotypic differentiation
1. Trigger conversion of wolffian ducts to male ejaculatory system
2. Direct the differentiation of the urogenital sinus and the external genitalia
2) Determine male secondary sexual characteristics
1. Development of both internal/external genitalia
2. Adult maturation of the external genitalia and accessory sexual organs
3. Deepening of vocal patterns (men) and patterns of hair growth
3) Muscle development and growth
**anabolic and androgenic effects
Term
Feminization syndrome
Definition
In testosterone-deficient states caused by inadequate secretion or disordered androgen action, the testes of the genetic males often fail to descend.
*this abnormality can be seen in individuals with both 5-alpha reductase deficiency and complete androgen resistance. (testicular feminization syndrome)
Term
Cryptorchidism
Definition
A disorder related to androgen deficiency where there is an abnormal retention of the testes in the abdominal cavity.
It causes severe damage to the seminiferous tubules and diminished testicular function.
Term
What are the stages of testicular descent and when does it occur?
Definition
Occurs in three stages during the last two thirds of gestation:
1) Movement of the testes to the inguinal region
2) Herniation of the abdominal wall to the gubernaculum
3) Descent of the testes into the scrotum. The gubernaculum acquires a similar diameter to the testis. As it's proximal portion degenerates, the gubernaculum draws the testis into the scrotum through the processus vaginalis
Term
Male pseudohermaphroditism
Definition
Affected individuals have a normal male karyotype (46 XY) and unambiguous male gonads but ambiguous external genitalia or many phenotypically appear as females.
Term
5-alpha reductase deficiency
Definition
This enzyme is necessary for the conversion of testosterone to DHT. Without, DHT dependent development may not occur (male pattern development of the urogenital sinus and external genitalia).
Term
Hypospadias
Definition
Developmental anomaly in which the urethra opens inferior to its usual location; usually seen in males with the opening on the underside of the penis.
A symptom of a 5-alpha reductase deficiency.
Term
AMH (antimullerian hormone) deficiency
Definition
When you lack this hormone, an individual develops into a female because the mullerian ducts do not degrade and allow the wolffian ducts to develop into the male uro-genital tract.
Term
True or false:
The testes, epididymis, male accessory glands, and erectile tissue of the penis receive mono-stimulation from the sympathetic nervous system
Definition
False. It receives stimulation from both the sympathetic and parasympathetic nervous system.
Term
True or false:
The testes, epididymis, male accessory glands and erectile tissue of the penis receive motor and sensory innervation through the pudendal nerve.
Definition
True.
Term
What are the major efferent pathways for the regulation of penile erection
Definition
Pelvic nerve (parasympathetic)
Right/left hypogastric nerve (sympathetic)
Pudendal nerve (somatic)
Term
The generation of an erection is primarily controlled by which nervous system?
Definition
By the parasympathetic nervous system.
so the processing of rigidity:
NO --> sGC --> cGMP --> PKB --> sequestration of intracellular calcium --> as [calcium] falls then the tissue relaxes and blood flows in.
Term
True or false: the sympathetic nervous system is responsible for tubenescence (penile erection)
Definition
False. The parasympathetic nervous system has primary responsibility for it.
Term
True or false:
cAMP starts the cascade that leads to the relaxation of the corpora cavernosa and corpus spongiosum and tumescence
Definition
False.
cGMP is the secondary messenger in the cascade that leads to the relaxation of the corpora cavernosa and corpus spongiosum. NO is the agonist that activation sGC, converting GTP to cGMP.
Term
How is NO production triggered? How does this tie into achieving an erection?
Definition
Acetylcholine, which is also secreted by the pelvic nerve, belonging to the sympathetic nervous system, binds to the M3 muscarinic receptor on endothelial cells. Acting through the g-coupled protein Galpha(q) PLC is stimulated and intracellular [Ca] is increased when PIP3 is converted into IP3 and DAG, leading to the activation of NO synthase and local release of NO.
Term
Atropine
Definition
A chemical that is found in muscles. It is an antagonist of acetylcholine receptors - but it is non selective and the therapeutic index is very narrow.
Term
Describe the sympathetic control over penile erection or relaxation.
Definition
Sympathetic nervous system causes the opposite reaction as the parasympathetic. Parasymp = rigidity. Sympathetic = flacidity.

While counterintuitive, the reason that the sympathetic nervous system causes flacidity is because of the vasoconstrictive effects of adrenalin and noradrenalin, which have the opposite affects as NO.

Blood vessel constriction limits the amount of blood able to flow into the penis and therefore blocks the penis' ability to achieve erection.
Term
Describe the somatic control over erection?
Definition
Somatic fibers innervate striated penile muscles.
Contraction of the striated ishiocavernosus muscle (during final phase of erection) increases pressure inside the corpora cavernosa
Contraction of the striated bulbospongiosus muscle increases engorgement of the corpus spongiosum and thus the glans penis by pumping blood up from the penile bulb underlying the muscle.

**mostly, however, these fibers play a part in the ejaculation of the semen and not in the initiation of the erection.
Term
True or false: seminal emission is primarily under parasympathetic control
Definition
False. It's primarily under sympathetic control
Term
Describe proper seminal emission:
Definition
Result of peristaltic contractions of the ampullary portion of the vas deferens, the seminal vesicles and the prostatic smooth muscles.
At the same time there is constriction of the internal sphincter of the bladder, which is under sympthatic control, thus preventing retrograde emission of sperm Into the urinary bladder.
Term
What are the two main kinds of penile dysfunctions?
Definition
Erectile and emission dysfunctions.
Emission (ejaculatory) dysfunction - often has to do with either emission at an inappropriate time or retrograde emission.
Erectile dysfunction - issue in developing or sustaining an erection during sexual intercourse.
Term
How do drugs like viagra, levitra, or cialis work?
Definition
By perpetuating the effects of the cGMP on the corpus cavernosum generated from the NO pathway. They do this by inhibiting the enzyme that breaks down cGMP, cGMP-specific phosphodiesterase type-5.

However, this effects both the cGMP-dependent phosphodiesterase here as well as in the eyes - causing a side effect called "blue vision".
Term
hCG is closely related to what other hormone?
Definition
LH
Term
What is the role of hCG?
Definition
Key for the suppression of hypersensitive immune reaction.
Sustains the corpus luteum as maternal levels of LH fall. Also has immunosuppresive characteristics, growth promoting ability, acts as an autocrine growth factor that promotes trophoblast growth and placental development.
Term
What immunosuppressive agents are released by the blastocyst?
Definition
hCG
Immunosuppressive factor
Prostaglandin E2
Interleukins 1alpha and 6
Interferon-alpha
Term
In-vitro fertilization.
Definition
A procedure in which oocytes are removed from a woman and fertilized with sperm under laboratory conditions.
Term
What are the important hormones that the placenta excretes?
Definition
hCG,
TSH,
Placental-variant growth hormone,
hCS1 and hCS2 (human placental lactogen)
TRH
CRH
GHRH
GnRH
Substance P (NT in the brain that helps u detect pain)
Neurotensin (regulates LH)
Somatostatin (important growth hormone)
Progesterone
Estradiol/estrone/estriol
Term
How does the ovarian stimulation step of in vetro fertilization occur?
Definition
Combination of FSH and LH or pure FSH preparations are given either intramuscularly or subcutaneously. Stimulates the maturation of several follicles at once.
GnRH analogs are administered prior to initial gonadotropin therapy. This prevents premature LH surge and ovulation.
Term
What stimulates the final maturation of the ovum? When else is this a useful action.
Definition
A surge of LH.
This also happens in in-vitro fertilization.
Term
Which estrogen is unimportant during any time other than pregnancy?
Definition
Estriol
Term
What hormones does the placenta lack during pregnancy and what contributes these required hormones?
Definition
Lacks:
Adequate cholesterol-synthesizing capacity
17-alpha hydroxylase (need for synth estrone and estradiol)
17,20-desmolase (need for synth estrone and estradiol)
16alpha-hydroxylase (needed for synth estriol)

The fetal adrenal gland and liver supplies:
17-alpha hydroxylase, 17,20-desmolase, 16alpha-hydroxylase
Term
What hormones does the fetus lack during pregnancy? What contributes the difference in required hormones?
Definition
Lacks:
3-Beta-hydroxysteroid dehydrogenase (HSD) (converts prognenol one to progesterone)
Aromatase (converts dehydroepiandrosterone (DHEA) to estradiol)

The placenta contributes them
Term
How does the maternal-placental-fetal unit work?
Definition
There's a balance of hormones wherein different structures contribute different enzymes that the others do not possess in order to produce the full complement of hormones.

Mother: contributes LDL cholesterol, but lacks adequate synthetic capacity for estrogens and progesterone.

Placenta: (after 8 weeks)
Lacks:
Adequate cholesterol-synthesizing capacity
17-alpha hydroxylase (need for synth estrone and estradiol)
17,20-desmolase (need for synth estrone and estradiol)
16alpha-hydroxylase (needed for synth estriol)

The fetal adrenal gland and liver supplies:
17-alpha hydroxylase, 17,20-desmolase, 16alpha-hydroxylase

Lacks:
3-Beta-hydroxysteroid dehydrogenase (HSD) (converts prognenol one to progesterone)
Aromatase (converts dehydroepiandrosterone (DHEA) to estradiol)
Term
Does the corpus luteum produce hormones?
Definition
Yes. During the secretory phase or the beginning of pregnancy, it secretes progesterone and some estrogens.
Term
What hormones do the fetus contribute to the maternal-placental-fetal unit.
Definition
Fetal adrenal gland and liver contribute:
17alpha-hydroxylase
17,20-desmolase
16alpha-hydroxylase
Term
What hormones do the placenta contribute to the maternal-placental-fetal unit.
Definition
3beta-hydroxysteroid dehydrogenase (prognenolone->progesterone)
Aromatase (DHEA --> estradiol)
Term
Why would you propose that a mothers blood volume and cardiac output would increase during pregnancy?
Definition
Elevated progesterone and estrogen cause vasodilation that decreases peripheral vascular resistance and thus renal perfusion (less expulsion from bowmans capsule due to drop in blood pressure).
During pregnancy response to ANGII decreases, stimulating production of aldosterone - increasing water retention.
Term
Pre-eclampsia
Definition
Characterized by high blood pressure (due to increase in circulating volume)(hypertension) and high levels of protein in the urine.
Term
How does mean arterial pressure change during pregnancy
Definition
It drops in the mid-pregnancy and then rises again in the third trimester

Reason:
Decrease in vascular resistance (progesterone/estrogen)
Term
Which position would give the mother the lowest blood pressure but highest cardiac output?
Definition
Left lateral recumbant. (laying on your left side)
Term
Describe the mechanisms behind the formation of arachidonic acid and prostaglandins
Definition
Direct pathway:
An agonist binds to a receptor that activates PLA2 which releases arachidonic acid (AA) from the membrane phospholipid

Indirect pathways:
1) Agonist binds to receptor that activates PLC, leading to the formation of DAG and IP3.
a. DAG lipase then releases AA from DAG.
2) IP3 releases Ca from internal stores, which leads to the activation of PLA2 - entering the direct pathway.
3) Mitogen-activated protein stimulates PLA2, releasing AA.
Term
Prostaglandins
Definition
PGD2, PGE2, PGF2alpha.

PGE2 and PGF2alpha are very important for birth - a woman given high concentrations of those at any time throughout gestation will experience contractions.

They supplement the activities of oxytocin, stimulating the contraction of the uterus.
PGF2alpha promotes the formation of gap junctions between uterine smooth-muscle cells. (estradiol does this too)
Prostaglandins induce softening, dilation and thinning out of the cervix, which occurs early during labor.

They are key in sensing pain during inflammation or headaches.
Term
Prostacyclin
Definition
Substance produced from arachidonic acid.
Has a vasodilatory effect - decreases clotting and thins the blood.
Term
Thromboxanes
Definition
Key for normal blood coagulation.
Term
Meiosis
Definition
Process of cellular division that occurs in germ cells, producing four haploid gametes.
meiosis 1) Recombination and separation of homologous chromosomes
Meiosis 2) chromatids separate
Term
What are the germ cells called in males and females?
Definition
Males: spermatogonia
Females: oogonia
Term
The phases of meiosis
Definition
The phases of meiosis:
Meiosis 1:
1) Interphase
2) Prophase
3) Metaphase 1
4) Anaphase 1
5) Telophase 1
Meiosis 2:
1) Interphase 2
2) Metaphase 2
3) Anaphase 2
4) Telophase 2
5) Cytokinesis
Term
Whats the difference in meiosis between males and females?
Definition
Males produce 4 spermatocytes for each cell reproduced.
In females there is only 1 oocyte and 2 polar bodies that are produced.
Term
When is the genetic sex of a zygote established?
Definition
At fertilization
Term
What does the genotypic sex determine?
Definition
The gonadal sex.
Term
What does the gonadal sex determine?
Definition
The phenotypic sex which becomes fully established at puberty.
Term
What determines gonadal sex?
Definition
Female sex occurs by default.
Male sex requires the presence of a Y chromosome, testosterone and TDF (testes determining factor) (TDF = SRY {sex-determining region Y})
Term
Where is the testes determining factor found?
Definition
It is also known as the SRY for sex-determining region Y. It is found on the short arm of the y chromosome.
Term
A phenotypically male individual has an XX genotype. What would we say he is?
Definition
A true hermaphrodite
Term
How do XX males occur?
Definition
Through an abnormal exchange of genetic material between X and Y chromosomes in the father. Causing transfer from the y to X chromosome.

ALSO:
If the sperm fertilizes an ovum with the defective X chromosome (has TDF) then it will also result in an XX male.
Term
What are key features about XX males?
Definition
They are sterile
They have small testes
May display feminine characteristics (all the way to breasts)
Term
Gonadal Dysgenesis
Definition
Characterized by abnormal gonadal differentiation..
Loss of one X
Term
Turner Syndrome
Definition
Example of gonadal dysgenesis.
Karyotype 45,XO
Characterized by short stature, amenorrhea, sexual infantilism (ETC)
Term
Individuals with XO chromosomes would have what typical symptoms?
Definition
Ovarian dysgenesis
- Gonads appear as a streak (line) on the pelvic sidewall in the adult.
Term
Difference between primary and secondary amenorrhea?
Definition
Primary: lack of menstrual cycle (ever)
Secondary: loss of menstrual cycle
Term
True hermaphrodites
Definition
Possess both female and male sex organs. Have no discernible Y-chromosome but do have testes.
46,XX Caused by one of the X chromosomes have TDF (SRY)
Term
Describe the association between leydig and sertoli cells
Definition
Leydig cells have receptors for LH whereas sertoli cells have FSH receptors.

When LH binds to the g-protein receptors on the leydig cells, it initiates a cascade of responses (cAMP-->PKA) leading to increased testosterone production by synthesizing SCP (sterol-carrier protein) and SAP2 (sterol-activating protein).
Some of the testosterone produced here goes into the nearby sertoli cells.

FSH binds to g-protein receptors on the sertoli cells, initiating the cAMP-PKA cascade to the synthesis of inhibins, ABP (androgen binding protein), Aromatase, Growth factors {which act on the leydig cells} and other products.
Some of the testosterone that comes in from the leydig cells are then converted into estradiol by aromatase.
Term
What are the names of the proteins that are produced in response to FSH? Where are they produced?
Definition
Inhibins, ABP (androgen binding protein), p-450 aromatase, growth factors

They're produced in the sertoli cells.
Term
Describe how growth factors produced in the sertoli cells affect the leydig cells?
Definition
Stimulatory effect on spermatogenesis. Also may increase the number if LH receptors on the leydig cells (leading to an increase in steroidgenisis)
Term
Inhibins
Definition
The granulosa and sertoli cells of the ovaries and testes are the primary source of inhibin in humans.
Have both paracrine/autocrine actions and, in males, plays an important negative feedback role in the hypothalamic-pituitary-testicular axis (for the production of FSH).
Term
What is the rate limiting step in the synthesis of testosterone?
Definition
The conversion of cholesterol to pregnenolone by p450-SCC (20,22-desmolase)
Term
Which are the p450 enzymes? Where are they found?
Definition
Found in the leydig cells
They're part of the enzymes that convert cholesterol to testosterone.
Term
Describe testosterone synthesis.
Definition
1) Starts in the mitochondria
1. P-450SCC (20,22-desmolase) removes the side chain, converting cholesterol into pregnenolone.
Term
Which hormone is the overall regulator of overall testosterone synthesis in the leydig cells?
Definition
LH - luteinizing hormone.
Term
How does LH stimulate and regulate testosterone synthesis in the leydig cells?
Definition
Increases the affinity of the enzyme (p-450SCC (20,22-desmolase) or "p-450 side chain cleavage enzyme" ) for cholesterol

Long term action is through the stimulation of the synthesis of the SCC enzyme, which increases steroidogenesis in the testis
Term
What is cholesterol called with its side chain removed? What's the name of the enzyme that does this?
Definition
The enzymes is p-450SCC
It converts cholesterol into pregnenolone.
Term
Which enzymes for the conversion of cholesterol to testosterone is found in the mitochondria?
Definition
p-450SCC or 20,22-desmolase
Removes the side chain from the cholesterol molecule converting it into pregnenolone.
Term
Which enzymes for the conversion of cholesterol to testosterone are found in the smooth endoplasmic reticulum.
Definition
21-alpha hydroxylase
11-beta hydroxylase
3-beta hydroxysteroid dehydrogenase
Term
What is the target of the anterior pituitary hormone produced by GHRH.
Definition
GH is produced by the anterior pituitaries somatotrophic cells due to stimulation by GHRH. GH stimulates IGF-1 production by multiple somatic tissues, especially liver.
Term
5-alpha reductase
Definition
Converts testosterone to DHT (dihydrotestosterone)
Term
What substances other than testosterone are secreted by the testis?
Definition
Pregnenolone, progesterone, 17-hydroxyprogesterone, androstenedione, androsterone and DHT.
Term
What tissues can produce testosterone and other androgens?
Definition
Adipose tissue, skin, adrenal cortex, testis (mostly this one)
Term
Describe the basic actions of an androgen receptors.
Definition
Androgens diffuse into target cells and act by binding to androgen receptors (present in genital tissues).
The androgen receptor functions as a homodimer (AR/AR) and is a type of nuclear receptor (works by stimulating transcription/translation)
Binds to the Hormones (or steroid) response element portion of the DNA strand.
Congenital absence of the androgen receptor (or production of abnormal androgen receptor) leads to a syndrome known as "testicular feminization"
Term
What leads to testicular feminization?
Definition
Malfunctioning or lack of androgen receptors.
Term
Describe the mechanism of action of testosterone and other steroid hormones
Definition
Androgen (the agonist) binds to a receptor that is found in either the cytosol or the nucleus.
Binding to this receptor causes a dimer to form with another activated receptor, increasing their affinity for binding to the SRE portion of the DNA strand.
The (homo/hetero)dimer binding to the SRE causes the transcription of proteins defined by those agonists.
Term
Activated steroid receptors bind to what?
Definition
First they form a homodimer and then they bind to the steroid response element of the DNA strand.
Term
Name the different nuclear receptors
Definition
Androgen receptor (AR/AR), glucocorticoids (GR/GR), mineralocortocoids (MR/MR), progestins (PR/PR), estrogens (ER/ER), vitamin D , thyroid hormone (THR/RXR), retinoic acid
Term
Gene coding for the androgen receptor is found on which sex-chromosome
Definition
On the x chromosome
Term
What enzyme catalyzes the production of DHT?
Definition
5-alpha reductase.
Term
Describe the control that the hypothalamic-pituitary-gonadal axis has over the menstrual cycle
Definition
Neurons in the hypothalamus' acruate nucleus and preoptic area of the hypothalamus synthesize, store and release GnRH which is carried by the long portal vessel to the anterior pituitary where the hormone binds to receptors on the surface of gonadotrophs resulting in the synthesis of FSH and LH.

LH stimulates theca cells (only produce progesterone)
FSH stimulates granulosa cells (produces both progesterone and estrogen)
Term
Which of the following produces estrogen and progesterone?
a) Theca cells
b) Granulosa cells
c) Leydig cells
d) A and B
e) B and C
Definition
B - Granulosa Cells.

They're the only ones that can produce both.
Theca cells can produce up to the intermediate androstenedione but that product is either converted into testosterone or it diffuses to the granulosa cell, where the enzyme aromatase can convert it into estrone. Subsequently the enzyme 17-beta HSD converts estrone to estradiol.

(it can also be converted to testosterone in the granulosa cells by 17-beta HSD)
Term
Aromatase does what?
Definition
Aromatase converts testosterone into estradiol and androstenedione into estrone.
Term
True or false:
It is testosterone that diffuses between theca and granulosa cell, which is then turned into estron and estradiol.
Definition
False.
Androstenedione is the diffusing intermediate molecule.
Term
Inhibins
Definition
Produced by the granulosa cells.
Exerts a negative feedback by stopping the pituitary from producing FSH when the levels of FSH increase (ONLY FSH) (at the level of the anterior pituitary)
Also have an intraovarian effect of decreasing androgen production.
Term
Activins
Definition
Produced and released by the granulosa cells. Responsible for causing positive feedback in the creation of LH. (at the level of the anterior pituitary)
Also have intraovarian effect of stimulating estrogen synthesis.
Term
True or false:
The granulosa cells have receptors for both LH and FSH
Definition
True.
Term
True or false:
The theca cells have receptors for both LH and FSH.
Definition
False! They only have receptors for LH.
Term
Describe the steps in the hypothalamic-pituitary-ovarian axis
Definition
Neurons in acruate nucleus / preoptic area of hypothalamus release GnRH.
@ anterior pituitary, GnRH binds to receptors on gonadotrophs and initiates PLC, DAG + IP3 cascade, triggering synthesis and release of LH and FSH.

LH binds to receptors on Theca cells, which initiates adenylyl cyclase -> cAMP -> PKA cascade, increasing transcription of proteins for synthesis of androgens.
Androgens enter the granulosa cells (from theca) and are converted to estrogens.

FSH binds to receptors on basolateral membrane of granulosa cells, activating PKA stimulating gene transcription and synthesis of relative enzymes (aromatase), activins, and inhibins.
Term
What molecules cause the negative feedback in the hypothalamic-pituitary-ovarian axis and where do they effect?
Definition
Activins/inhibins act on the anterior pituitary
Estrogens/progestins act on both the anterior pituitary and the hypothalamic neurons through interneurons.
Estrogens work at low/high []'s but progestins work only at high []'s.
Term
When are progestins highest?
Definition
During pregnancy. (progesterone)
Term
What key vasoconstrictor is produced from arachidonic acid?
Definition
HETE molecules.
Term
NSAIDS
Definition
Non-steroidal anti-inflammatory drugs
Term
True or false:
Aspirin cuts off the pathway that produces HETE molecules.
Definition
False.
It cuts off the pathway that makes prostacyclin, thromboxanes and prostaglandins.
Term
Parturition
Definition
The process of giving birth
Term
What are the stages of labor?
Definition
0 - uterine tranquility and lack of responsiveness to contraction
1 - uterine awakening, initiation of parturition, extending to complete cervical dilation.
**a physiological change occurs here, where more gap junctions are produced and inserted into the epithelia.
2 - active labor, from complete cervical dilation to delivery of the newborn.
3 - from delivery of the fetus to the expulsion of the placenta and "final uterine contraction".
Term
What is the precursor of prostaglandins?
Definition
Arachidonic acid
Term
In what type of cells are prostaglandins produced?
Definition
Decidual cells.
Term
If you want to induce labor, what would be a good thing to inject?
Definition
Prostaglandins in high concentrations.
Term
COX1
Definition
The enzyme that initiates the conversion of arachidonic acid to prostagladins/prostacyclins/thromboxanes.

This enzyme is inhibited by aspirin, blocking off the production of prostaglandins and potentially prolonging gestation, inhibiting labor.
Term
Where is oxytocin and vasopressin formed?
Definition
In the supraoptic and paraventricular nuclei of the hypothalamus.
Term
True or false: maternal oxytocin plays a pivotal role in the initiation of parturition.
Definition
False.
Fetal oxytocin plays a larger role in the initiation of parturition.
Term
Ferguson Reflex
Definition
A reflex that occurs when the cervix is distended, initiating the release of oxytocin.
Term
What are the agents involved in sustaining labor?
Definition
Oxytocin,
Progesterone,
Relaxin,
Prostaglandins PGF2 and PGE2
Term
What hormone stimulates the decidual cells to produce prostaglandins
Definition
Oxytocin
Term
What types of hormones affect the breasts
Definition
- Mammogenic (proliferation of alveolar and duct cells)
- Lactogenic (initiation of milk production by alveolar cells)
- Galactokinetic (contraction of myoepithelial cells and thus milk ejection)
- Galactopoetic (milk production after it has been established)
Term
SRY
Definition
Sex-determining region Y … is the same as TDF
Term
TDF
Definition
Is the same as SRY… testes determining factor
Term
Mixed gonadal dysgenesis
Definition
Individuals with testes and a streak ovary, 45,XO karyotype.

Some are pseudohermaphroditic --> This means that they did not have both types of gonadal tissue but still displayed morphological characteristics of both sexes.
Term
Which would have a more severe impact: SRY being moved from a Y-chromosome to an X-chromosome or an autosomal chromosome?
Definition
Movement to the autosomal chromosome would have severer impacts on the individual.
Term
Para-mesonephric duct
Definition
Is the same as the mullerian ducts.
Develops into the oviducts (fallopian tubes), uterus and upper third of the vagina.
Term
Mullerian ducts
Definition
Mullerian ducts
Term
Mesonephric ducts
Definition
Also known as the wolffian ducts and develops into the vas deferens, seminiferous tubules and ejaculatory duct
Term
Undifferentiated internal genital ducts:
Definition
the mesonephric or wolffian ducts and the paramesonephric or mullerian ducts are clearly distinguished.
Term
What is required for the differentiation of internal genital ducts into those for a males?
Definition
In the differentiated male duct system, the paramesonephric or mullerian ducts degenerates and the mesonephric or wolffian duct develops into the vas deferens, seminiferous tubules and ejaculatory duct.

Requires the presence of both testosterone and AMH (anti-mullerian hormone) … otherwise it falls into the female pattern
Term
Wolffian ducts
Definition
Also known as the mesonephric ducts… develops into the vas deferens, seminiferous tubules and ejaculatory ducts in males.
Term
The testes are removed from a developing embryo of a chimpanzee. Would we expect the chimpanzee to
a) Causes the wolffian duct to collapse and form female genitalia
b) Causes the wolffian duct to collapse and form male genitalia
c) Causes the mullerian ducts to collapse and forms female genitalia
d) Causes the mullerian ducts to collapse and forms male genitalia
Definition
A --> Would cause the wolffian duct to collapse and form female genitalia

Feminization occurs.
Term
AMH
Definition
Anti-mullerian hormone … also known as mullerian inhibiting substance (MIS)
Term
MIS
Definition
Mullerian inhibiting substance … also known as anti-mullerian hormone (AMH)
Term
How could you have a male genotypically but a female phenotypically?
Definition
By removing his testes during gestation. The lack of AMH and testosterone will cause wolffian ducts to degenerate and form into the female tubules.
Term
A male individual is found to lack AMH. How would we expect his genital ducts to develop?
Definition
Anti-mullerian hormone (AMH) is also known as mullerian inhibiting substance.
If it is lacking, then we would expect the male individual to develop in a female pattern. This means that we would expect the wolffian ducts to degenerate and the genetically male individual develops female genitalia internally and externally.
Term
which factors are indispensable for the formation of male genital ducts?
Definition
testosterone and AMH.
Term
Is there a time limit wherein gender must be decided?
Definition
yes, it is @ 9 weeks during foetal development.
Term
What is menopause?
Definition
When cyclic reproduction function ceases, menstruation stops and childbearing is generally no longer possible.

Only few functioning follicles remain in the ovaries of menopausal women

The levels of ovarian steroids (estrogen/progesterone) fall but the concentration of gonadotropins rises. Because of this loss the negative feedback mechanisms will begin to fail and the levels of FSH will increase.
Also, diminished inhibin production may contribute to this fact.
Term
What is it that causes hot flashes and night sweats?
Definition
Vasomotor instability, which is a symptom of menopause.
Term
What are the major consequences of menopause?
Definition
Vasomotor instability,
Hot flashes,
Night sweats,
Mood changes,
Short-term memory loss
Sleep disturbances, headaches
Loss of libido
Term
What are the physical changes that come with menopause?
Definition
Atrophy of the vaginal epithelium
Changes in vaginal pH
Decrease in vaginal secretions
Decrease in circulation to vaginal and uterus
Pelvic relaxation
Loss of vaginal tone
Cardiovascular disease / osteoporosis / alzheimers disease
Term
True or false: a womans libido will be increased around ovulation. This reaction is due to an increase in the production of androgens that occurs just before and during ovulation following the LH surge.
Definition
True.
Term
The female sexual response is composed of what stages?
Definition
Excitement,
Plateau
Orgasm
Resolution
Term
Sexual excitement in females is controlled by what branch of the nervous system?
Definition
By the parasympathetic fibers emanating from the sacral plexus that innervates erectile tissue.
Dilation of the blood vessels in the erectile tissue causes engorgement and erection of the clitoris.
Term
The female orgasm
Definition
Is coordinated through a spinal cord reflex that results in rhythmic contractions of the perineal muscle.
Afferent pathways for this follow the pudendal nerves (are the primary innervation for the perineum and the female external genitalia)
Term
Where does fertilization occur?
Definition
In the ampulla, the upper third of the fallopian tube or the oviduct
Term
Ectopic pregnancy
Definition
A condition where implantation occurs anywhere along the fallopian tubes
Term
Capacitation
Definition
The physiological process by which spermatozoa acquire the ability to penetrate the zona pellucida of the ovum.
This occurs in the female reproduction tract, on the way to implantation.

Removal or modification of a protective protein coat from the sperm cell membrane is an important molecular event in the capacitation.
Term
What are the names of the structure that the spermatozoa must penetrate in order to fertilize the ovum? (from most superficial inwards)
Definition
The corona radiata
The zona pellucida
Term
What are the steps in fertilization
Definition
1) Sperm head weaves its way past the follicular cells and attaches to the zona pellucida that surrounds the oocyte. (ZP1, ZP2, ZP3)
2) As a result of the sperm-ZP3 interaction, the sperm undergoes the acrosomal reaction.
1. During which elevated calcium levels triggers the fusion of the outer acrosomal membrane with the sperm cell membrane leading to exocytosis of hydrolyzing enzymes
3) The hydrolyzing enzymes allow the spermatozoon to penetrate through the zona pellucida
4) Cell membranes of the sperm cell and oocyte fuse- microvilli on the oocyte surface envelops and binds to the sperm
5) Spermatozoon penetrates oocytes membrane initiating ip3 reaction (^[calcium]).
1. The rise in [calcium] triggers the oocytes second meiotic division and the cortical reaction. Second polar body with haploid chromosomes formed.
6) Oocyte completes its second meiotic division, forming second haploid polar body.
1. The nucleus of the mature ovum becomes the female pronucleus
7) The sperm nucleus decondenses and transforms into the male pronucleus
8) The male and female pronuclei fuse, forming a new cell, the zygote.
Term
The zona pellucida
Definition
Surrounds the oocyte.
Composed of three glycoproteins: ZP1, ZP2, ZP3

**it is ZP3 that is the most important because it is the binding of the spermatid and ZP3 that triggers the acrosome reaction.
Term
Morula
Definition
Fertilized ovum, about 12 or more cells, that resides in the fallopian tubes for about 3 days, receiving nourishment from the fallopian tube secretions.
Term
How is the egg propelled through the uterus?
Definition
Propelled through the isthmus of the fallopian tube to the uterus by beating the cilia of the tubal epithelium and contraction of the fallopian tube.
Term
hCG
Definition
Hormone that stops the rejection of the blastocyst. Stops hypersensitive immune reaction.
Term
What produces hCG?
Definition
Produced by the female and blastocyst
Term
Describe the steps after fertilization, leading up to implantation, of the blastocyte.
Definition
Fertilized ovum resides in the fallopian tube for ~3 days during which time it develops to the morula stage.
Is later propelled thru isthmus of fallopian tube to uterus by beating cilia of tubule epithelium + contraction of the tube
Enters uterine cavity, turns into blastocyst, floats freely for about 72 hrs.
Implantation occurs ~ 6-7 days following ovulation.
@ about 9-10 days after ovulation predecidualization begins and stromal cells turn into decidual cells.
These decidual cells spread across the superficial layer of the endometrium, forming the zona compacta and separating it from the zona spongiosa.
Term
Why is it that women who have given birth recently cannot get pregnant again?
Definition
So long as a woman is breast feeding, she will have reduced gonadotropin release. There won't be adequate levels of progesterone or estrogen to achieve pregnancy because of this.
Term
Describe the formation of milk in the breast.
Definition
- Breast consists of a series of secretory lobules, which empty into ductules.
• The lobules are made up of many alveoli
○ Each alveolus consists of secretory epithelial cells that actually secrete milk as well as contractile myoepithelial cells
- Ductules empty into ducts and ducts empty into the ampulla.
Term
What is the composition of milk?
Definition
Milk is an emulsification of fats in an acqueous solution containing sugar (lactose) proteins (lactalbumin and casein) and several cations (K, Ca, Na) and anions (Cl and phosphate)
Term
Would it be okay to give your child cows milk instead of human milk in the first few months of age?
Definition
No. the composition is different : cows milk has higher protein (higher casein concentration) and higher electrolyte concentration.
Term
Describe the let down reflex:
Definition
The suckling effect stimulates sensory nerves, which carry the signal from nerve to spinal cord where they synapse with neurons to the brain.
In the acruate nucleus of the hypothalamus, the afferent input from the nipple inhibits neurons that release dopamine… DA travels down to the anterior pituitary where it inhibits prolactin. (PRL)
In the paraventricular and supraoptic nuclei of the hypothalamus, the afferent input from the nipple triggers the production and release of oxytocin.
The afferent impulse from the nipple also inhibits GnRH release.
Term
Enzyme that converts androstenedione to estrtone (then esttradiol)
Definition
Aromatase
(then 17-beta HSD)
Term
Product when androstenedione attaches to the active site of aromatase
Definition
estrone
Term
Cells that produce inhibins, activins, and aromatase
a) Theca
b) Leydig
c) Granulosa
d) Sertoli
Definition
C - granulosa
Term
What is the two-cell, two-gonadotropin hypothesis?
Definition
Follicular Stage:
1) LH stimulates the theca cell, via adenylyl cyclase pathway to increase synthesis of LDL receptors and the side-chain cleavage enzyme.
1. Theca cell increases production of androstenedione
2) androstenedione produced in theca cells freely diffuses to the granulosa cells nearby.
3) FSH, acting via the adenylyl cyclase pathway, stimulates the granulosa cells to produce aromatase.
4) Aromatase converts androstenedione to estrone.
1. 17-beta hydroxysteroid dehydrogenase (17beta HSD) then converts estrone into estradiol
a. ***this step can also occur a different way where androstenedione is first converted to testosterone by 17-beta HSD and then aromatase converts it to estradiol.
5) Estradiol diffuses into the blood vessels.

Luteal Stage:
- Increased vascularization leads to increase progesterone and 17alpha-hydroxyprogesterone biosynthesis.
○ The granulosa-lutein cells lack the protein that has dual activity for 17-alpha hydroxylase and 17,20-desmolase. Thus it necessitates that progesterone first moves to the theca-lutein cell, which converts pogesterone to 17alpha-hydroxyprogesterone as well as androstenedione.
- Estradiol synthesis requires the movement of androstenedione from the theca-lutein cell to the granulosa-lutein cell for aromization.
Term
Which enzyme is it that the ovaries has that enables them to produce estrogen that the males do not?
Definition
Aromatase
Term
Which hormone peaks on the day you ovulate? Which hormone peaks right beforehand?
Definition
LH peaks a few hours before ovulation occurs.
Estrogen peaks days before.

FSH peaks on the day of ovulation.
Term
Why do women have nearly twice the concentration of "testosterone binding globulin" (TeBG) in their blood?
Definition
Because women take birth control pills - estrogens stimulate the synthesis of SHBG - sex hormone binding globulin (TeBG)
Term
Which cells of the ovaries produce estrogen?
Definition
Granulosa cells
Term
Which hormone is most important during the follulcar phase of the menstrual cycle?
Definition
Estrogen
Term
Which hormone is most important during the luteal phase of the menstrual cycle?
Definition
Progesterone
Term
When does the endometrial cycle fall with relation to the menstrual cycle?
Definition
The menstrual cycle is broken down into follicular and luteal phases.
The endometrial cycle is broken down into menses, proliferative phase and secretion phase.

The menses and proliferative phase fall into the follicular phase of the menstrual cycle.
The secretion phase occurs through the luteal phase of the menstrual cycle.
Term
The menstrual phase
Definition
Part of the endometrial cycle. Occurs during the follicular phase of the menstrual cycle.
[estrogen] reduce greatly, progesterone increases and this causes the degeneration of the corpus luteum.
Glandular/vascular integrity of endometrium breaks down when the hormonal support of the endometrium is withdrawn - leading to menstruation.
Afterwards, only a thin layer of non-epithelial (matrix) cells are left in the inner walls of the uterus.
Term
The proliferative phase
Definition
Part of the endometrial cycle. Occurs during the follicular phase of the menstrual cycle.

- Proliferation of the basal stromal cells on the surface of the uterus (zona basalis) as well as the proliferation of the epithelial cells. Endometrium is restored by about the 5th day and continues until the third dayish after ovulation.

Prolif/differentiation of the endometrium are stimulated by estrogen. Estrogen rises rise early in the follicular phase and peak just before ovulation.

*the level of endometrial estrogen receptor increase during the follicular phase and are higher during proliferative phase but decline after ovulation as a result of changes in progesterone lvls.

It is ended by the anti-estrogen effects of progesterone.
Term
Estrogen, in the proliferative phase, induces the secretion of what?
Definition
Growth factors.
TGF, IGF, EGF
It also induces the synthesis of progestin receptors in the endometrial tissue in preparation for the luteal phase.
Term
Progesterone opposes the action of estrogen by
a) Increasing the transcription of growth factors
b) Stimulating 17beta-HSD and sulfotransferase, which convert estradiol to estrone
c) Increasing ovulation
d) Spontaneously ejecting endometrium
Definition
B - stimulating 17-beta HSD and sulfotransferase causes a conversion of estradiol to the less active estrone and other biologically inactive molecules.
This halts the proliferation phase of the endometrial cycle.
Term
The secretory phase.
Definition
Part of the endometrial cycle.
Progesterone ends the proliferation phase by stimulating the enzyme 17-beta HSD.
It also increases vascularization of the endometrium in preparation for the blastocyst.
Term
How is the proliferative cycle ended?
Definition
When the concentrations of progesterone start increasing, it carries an anti-estrogen effect where it stimulates 17-beta HSD and sulfotransferase which convert estradiol to less active forms (estrone, etc).
Term
What are the layers of the endometrium?
Definition
Superficial zona compacta
Mid-level zona spongiosa
(the top two make up the |functional layer|)
Zona basalis = deepest layer that remains after birth or menstruation.
Term
Ischemic phase
Definition
Occurs at the end of the secretory phase of the endometrial cycle. The levels of progesterone and estrogen both begin to drop and this leads to the demise of the upper two thirds of the endometrium.
Term
Why doesn't menstrual blood clot?
Definition
Because of the presence of fibrolysins which are released by necrotic endometrial tissue.
Term
When is estradiol at its peak during the menstrual cycle?
Definition
It is at its peak a few days before ovulation - when the egg is completely mature.
Term
What are the different categories of birth control pills?
What is their mechanism of action?
Definition
1. Monophasic or fixed-combination oral contraceptives
1. 21 day cycle of identical pills
2. Multiphasic or varying-dose pill
1. Generally maintain a low dose of estrogen throughout the cycle with varying amounts of progestin.
3. Progestin-only oral contraceptive pill ("mini-pill")

Reduce the secretion of GnRH at the level of the hypothalamus and at the level of the gonadotrophs in the anterior pituitary by feedback mechanism. (supressed secretion of the gonadotropins LH and FSH.)
Term
What are the most important vasoconstrictors in physiology?
Definition
Angiotensin, endothelin, 20-HETE (20-hydroxyeiocosatetraenoic acid)
Term
What do oral contraceptives decrease the risk of?
Definition
Ovarian cancer
Endometrial cancer
Ovarian retention cysts
Ectopic pregnancy
Pelvic inflammatory disease
Benign breast disease
Term
Oral contraceptives increase the risk of what?
Definition
Benign liver tumors
Gallstones (cholelithiasis)
Hypertension (vasoconstrictors!)
Heart attack
Stroke
Deep vein thrombosis
Pulmonary embolus
Term
The g-protein receptor in gonadotrophs is
a) Gαa
b) Gαe
c) Gαq
d) Gαs
Definition
C - Gαq
Activates PLC cascade in which DAG activates PKC (initiating transcription of new FSH and LH molecules) and IP3 initiates the exocytosis of the vesicles containing FSH and LH.
Term
Describe the positive feedback of ovarian steroids.
Definition
At the end of the follicular phase, ovarian steroids have a positive feedback effect on the hypothalamic-pituitary axis + the gonadotrophs of the anterior Pit.
Estrogen levels gradually rise during the follicular phase and @ a certain threshold the hypothalamic pituitary axis reverses its sensitivity to estrogens.
Increases the sensitivity of the gonadotrophs of the anterior pituitary to GnRH.
Term
Clinical problems requiring increased gonadotropin secretion by the gonads are treated by:
a) Continuous mode of administration of GnRH
b) Pulsatile administration of GnRH
c) Daily administration of GnRH
d) Administration of gonadotropins directly
Definition
B - pulsatile administration of GnRH

Example: Kallmann syndrome. Caused by disordered migration of the GnRH cells during embryonic development.
Term
Clinical problems requiring gonadal inhibition, it is treated by means of:
a) Continuous mode of administration of GnRH
b) Pulsatile administration of GnRH
c) Daily administration of GnRH
d) Administration of gonadotropins directly
Definition
A - continuous mode of administration (of GnRH)

Example: endometriosis. Caused by endometrial tissue located outside the uterine cavity. Continuous administration inhibits replenishment of the GnRH receptors in the gonadotrophs in the anterior pituitary. Causes hypoestrogenism which leads to diminuation of endometriotic tissue.

2nd example:
Leiomyomas - a type of smooth muscle tumor of the uterus. It is estrogen dependent. Reduction in estrogen results in a reduction in the proliferation of tumor-related lesions.
Term
Kallmann syndrome.
Definition
Caused by disordered migration of the GnRH cells during embryonic development. Treated by pulsatile administration of GnRH.
Term
True or false: estrogen biosynthesis requires only one cell
Definition
False. It requires two cells and two gonadotropins.
Cells: theca/granulosa (follicular phase)
Theca-lutein/granulosa-lutein (luteal phase)
Term
When would you be in your follicular phase, or your luteal phase?
Definition
The day before ovulation you're in your follicular phase. The day after you're in your luteal phase.
Term
Which is more superficial - the granulosa cells or the theca cells
Definition
The theca cells are more superficial - making them closer to the blood vessels compared to granulosa cells (during the follicular phase).
Term
What do the theca or granulosa cells have that the other does not.
Definition
The theca cells have the enzymes required to make 'adrenal androgens' (17alpha hydroxylase/17,20-desmolase) but lack aromatase (converts those androgens to estrogens)
The granulosa cells have aromatase but lack the adrenal androgen making hormones.
Term
True or false: During the follicular phase, the granulosa cells obtain most of their cholesterol from LDL's in the blood stream.
Definition
False. Due to their depth, they are further away from direct blood sources and LDL molecules. They therefore produce their cholesterol de novo until they enter the luteal phase and vascularization occurs leading to a dramatic increase in the production of progesterone.
Term
What is the name of the g-protein coupled receptor found on theca cells:
A) GalpaQ
B) GalphOlf
C) GalphaS
D) GalphaC
Definition
C - Gαs

Initiates a cAMP - PKA pathway when LH binds to the receptors on Theca cells surface. PKA causes the transcription/translation of the enzymes that are responsible for converting cholesterol to prognenolone.
Term
true or false: the cells of the external male genitalia produce DHT.
Definition
True!
they possess 5alpha-reductase which converts testosterone into DHT.
Term
If an individual lacked the enzyme 5alpha-reductase, what would we expect its development to be like if its male?
Definition
so long as it had normal testosterone and AMH production, the lack of 5alpha-reductase would result in an absence of DHT.
DHT is responsible for the maturation of the external genitalia, and therefore there will be normal development of the wolffian ducts but impaired virilisation of the external genitalia.
Term
which are the enzymes who, when deficient, cause congenital feminine hyperplasia?
Definition
21-alpha-hydroxylase (SER)
11-beta-hydroxylase (Mitochondria)
3-beta-hydroxysteroid dehydrogenase (SER)


((lead to virilization in females and thus hypersecretion of adrenal androgens. It also leads to a decreased production of aldosterone, causing a drop in blood pressure and increased secretion of water and salt.
Term
where are the enzymes 21-alpha-hydroxylase, 11-beta-hydroxylase,3-beta-hydroxysteroid dehydrogenase located and what pathology are they involved in?
Definition
located in either the smooth endoplasmic reticulum or in the mitochondria.
Term
why does congenital feminine hyperplasia result in masculinization?
Definition
Because when the activities of one of the three enzymes (or all three of 21-alpha-hydroxylase (SER), 11-beta-hydroxylase (Mitochondria), 3-beta-hydroxysteroid dehydrogenase (SER)) are disabled, then other pathways will become more active (reagents shunted down another pathway) which is towards the production of testosterone and therefore masculinization.
Term
which is the enzyme which, when deficient, most commonly causes ambiguous genitalia in females?
Definition
21-alpha-hydroxylase (SER) primarily [95% of cases].
also
11-beta-hydroxylase (Mitochondria)
3-beta-hydroxysteroid dehydrogenase (SER)
Term
21-alpha hydroxylase deficiency
Definition
reduces the conversion of progesterone to 11-deoxycorticosterone, which goes on to form aldosterone… also reduces the conversion of 17alpha-hydroxyprogesterone to 11-deoxycortisol (the precursor to cortisol).

as a result of this, adrenal steroid precursors are shunted into androgen pathways.
Term
adrenogenital syndrome
Definition
occurs in female infants where a deficiency in key enzymatic pathways (21-alpha hydroxylase, 11-beta hydroxylase, 3-beta hydroxysteroid dehydrogenase) for steroid synthesis causes shunting of precursors into the androgen pathways.

external genitalia difficult to distinguish from male genitalia on visual inspection. (clit enlarged, looks like penis. labioscrotal folds are enlarged and fused to resemble a scrotum. …. thus male phenotype in otherwise female infant).
Term
feminization syndrome:
Definition
inadequate secretion or disordered androgen action may result in a testosterone deficient state. In such a case, the testes of genetic males often fail to descend.
may be caused by a 5-alpha reductase deficiency or complete androgen resistance.
Term
testicular descent is dependent on what type of hormone?
Definition
Testosterone
Term
5-alpha reductase deficiency
Definition
necessary for the conversion of testosterone to dihydrotestosterone. Deficiency may lead to ambiguous male genitalia.
Term
male pseudohermaphroditism
Definition
affected individuals have a normal male karyotype (46, XY) and unambiguous male gonads but ambiguous external genitalia (or may appear phenotypically as females).

can be caused by any defect in mechanisms by which androgens act on target tissues in genotypic males
Term
testicular feminization
Definition
occurs due to a congenital absence of androgen receptors or due to the production of abnormal androgen receptors.
Term
the formation of dihydrotestosterone:
Definition
the enzyme, 5-alpha reductase, which converts testosterone into DHT is found within the cytoplasm.
Term
true or false:
AMH is a homodimer of two monomeric glycoprotein subunits that are linked by disulfide bonds
Definition
true
Term
describe the actions of steroid hormones within the cell
Definition
steroid hormones move into the cell by simple diffusion across the membrane.
they then bind to their appropriate receptors either inside the cytosol or within the nucleus.
the binding of the hormone to receptor causes a change in conformation that promotes the formation of a dimer and increases the affinity for the SRE (steroid response element) on the DNA of the nucleus.
Term
A hormone that stimulates the release of another hormone is called what? What do they act on?
Definition
A tropic hormone.
Trophic cells! (gonadotrophs)
Term
What are the names of the hormones released by the anterior pituitary gland?
Definition
GH - growth hormone
TSH - thyroid stimulating hormone
ACTH - adrenocorticotrophic hormone
LH - leutenizing hormone
FSH - follicle stimulating hormone
PRL - Prolactin
Term
True or false:
The trophic cells found in the anterior pituitary act through a g-protein coupled cascade wherein PLC is activated and PIP3 gets broken down into IP3 and DAG.
Definition
True.
Term
Describe the actions of releasing hormones on the anterior pituitary trophic cells.
Definition
The binding of stimulatory hormones to the trophic cells of the anterior pituitary (gonadotroph etc) occurs through a g-protein coupled receptor which initiates a PLC cascade of reactions (PIP3 --> DAG + IP3) wherein IP3 causes a sequestration of calcium (interior) leading to calcium-induced calcium release and the DAG activates PKC which can go directly into the nucleus and cause transcription/translation of specific proteins which are related to the synthesis of that hormone.
Term
Gonadotropin-releasing hormone (GnRH) stimulates the release of what hormones?
Definition
Stimulates the gonadotrophs of the anterior pituitary to secrete the gonadotropins leutenizing hormone (LH) and follicle-stimulating hormone (FSH)
Term
The male hypothalamic-pituitary-gonadal axis is responsible for the control of what?
Definition
1) Production of gametes in the seminiferous tubules (spermatogenesis)
2) Androgen biosynthesis in the leydig cells in the testes.
Term
Where are the principle neurons that synthesize, store and release GnRH?
Definition
Primarily the acruate nucleus and the preoptic area.
Term
FSH and LH are
a) Primary gonadotropins
b) Secondary gonadotropins
c) Primary gonadotrophs
d) Secondary gonadotrophins
Definition
A
Primary gonadotropins
Term
Describe the GnRH actions at the cellular level.
Definition
G-protein coupled receptor, Gαq, activates PLC when activated. PLC breaks PIP3 down into IP3 and DAG. IP3 triggers calcium release from internal stores and DAG activates PKC which stimulates the transcription/translation of LH and FSH. The calcium released by IP3 triggers further release of calcium (calcium-induced calcium release) which results in the exocytosis of vesicles containing the hormones.
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