Term
| What are the levels of the female hormone system? |
|
Definition
Hypothalamus releases GnRH --> Anterior pituitary releases LH/FSH --> Ovaries release estrogen and progesterone
Levels not constant, vary on a 28-day cycle. GnRH released in 90 min pulses. |
|
|
Term
| What are the two main points of the monthly sexual cycle? |
|
Definition
- A SINGLE ovum is released from the ovaries each month
- Uterine endometrium is prepared in advance of the ovum. |
|
|
Term
| Where does fertilization take place? |
|
Definition
| In the ampullae. Sperm travels through the vagina --> cervix --> uterus |
|
|
Term
| What are the phases of the ovarian cycle? |
|
Definition
- Follicular phase - 1st-14 days driven by FSH
- Luteal phase - 14-28 days, corpus luteum active. Driven by LH, supports a fertilized egg
**Ovarian changes are concurrent with uterine changes.
**Ovulation on day 14 |
|
|
Term
| What are the stages of the uterus during the follicular phase? |
|
Definition
| Menstrual phase and proliferative phase |
|
|
Term
| What are the stages of the uterus during the luteal phase? |
|
Definition
| secretory phase and pre-menstrual phase |
|
|
Term
| What types of follicles are in the follicular phase? |
|
Definition
- Primordial follicles - gametocytes containing the ovum surrounded by granulosa cells (nourish ovum). Finite #. MIF prevents maturation
- Primary follicle - LH/FSH secretion. Additional layers of granulosa cells, moderate growth of ovum.
- Antrum - secondary follicle. Grows explosively in the presence of estrogen due to high FSH/LH receptors.
- Mature - the follicle that outgrows the others |
|
|
Term
| What organ is responsible for the bulk of female steroidogenesis? |
|
Definition
|
|
Term
|
Definition
| Outside granulosa cells, secrete androgens (testosterone and DHT) |
|
|
Term
| What do Granulosa cells secrete? |
|
Definition
| follicular fluid containing high concentrations of estrogen. |
|
|
Term
| When does ovulation occur? |
|
Definition
When a primary follicle --> secondary follicle which grows due to estrogen --> one follicle matures, the others reabsorb to primary follicles.
- Follicle ruptures and ovum expels into peritoneal cavity |
|
|
Term
| What is the corpus luteum? |
|
Definition
In the luteal phase, formed from the remaining granulosa and thecal cells.
Synthesizes and secretes mostly PROGESTERONE, some estrogen
- fertilized: corpus luteum persists for 3 months until placenta forms
- No fertilization: degeneration in about 10 days. |
|
|
Term
| What are molecular characteristics of the 1st 9 days? (Follicular phase) |
|
Definition
- FSH/LH are released
- Estrogen and progesterone are low
- endometrium lining is thin |
|
|
Term
| What are the effects of low estrogen release on the anterior pituitary? |
|
Definition
LH stimulates thecal cells to produce androgens --> diffusion to granulosa cells where it is converted to estrogen
LOW level: negative feedback and blocks LH/FSH from anterior pituitary. Blocks development of other follicles |
|
|
Term
| What are the molecular characteristics of days 9-12? |
|
Definition
- FSH/LH released -- LH in high frequency, low amplitude pulses
- Estrogen rises to a higher level
- Due to higher estrogen - FSH/LH decreases
- Endometrium proliferates |
|
|
Term
| What is the key mediator of uterine thickening? |
|
Definition
| ESTROGEN! increases layer and blood supply. Also increases progesterone receptors and thins cervical membrane to allow migration of sperm. |
|
|
Term
| What are the effects of high estrogen release on the anterior pituitary? |
|
Definition
Positive feedback - increased levels of FSH/LH --> LH/FSH SURGE
Surge happens on days 12-14 --. 2ndary follicle becomes mature follicle and ruptures |
|
|
Term
| What happens on days 14-16, after ovulation? |
|
Definition
Estrogen levels fall, decreasing LH/FSH
Prevents maturation of other follicles |
|
|
Term
| What are the molecular aspects of the luteal phase? |
|
Definition
LH surge transforms the ruptured follicle into the corpus luteum
Production of PROGESTERONE, estrogen, and inhibin.
Negative feedback on anterior pituitary, inhibition LH/FSH.
LH pulses are now high amplitude, low frequency. |
|
|
Term
| What is the key mediator of POST-ovulatory uterine effects? |
|
Definition
PROGESTERONE! Tissue becomes secretory and vascular.
Progesterone drives the thickening of the cervical mucous in the luteal phase |
|
|
Term
| What happens at the end of the ovarian cycle? |
|
Definition
If implantation does not occur, the corpus luteum degenerates, decreasing progesterone.
Without progesterone, cells die and arteries burst, leading to a sloughing of the wall. |
|
|
Term
| What role do prostaglandins play in the ovarian cycle? |
|
Definition
- LH/FSH surge --> cAMP-dependent upregulation of COX2 in granulosa and thecal cells --> ovulation by proteolysis
- If not pregnant, uterus secretes PgE and PgF, leading to lysis of the corpus luteum and menstruation. Pain and cramps.
- the pregnant or non-pregnant uterus is contracted by PgE or PgF. PGs in semen. |
|
|
Term
|
Definition
Permanant cessation of the menstrual cycle from loss of ovarian follicles at a mean age of 50.
Variation in FSH, estradiol falls.
Endogenous estrogen still produced by androgen conversion: Androstendione --> ESTRONE |
|
|
Term
| What are the symptoms of menopause? |
|
Definition
HA, hot flashes
Breasts droop
Weight gain
Backaches
Anxiety, depression
Vaginal dryness, itching
Bone loss |
|
|
Term
| How does fertilization take place? |
|
Definition
| In the ampullae, then for 3-5 days travels to the uterus, diving into the blastocyst. Implantation driven by trophoblastic cells |
|
|
Term
| What are hormones in pregnancy? |
|
Definition
- Human chorionic gonadotropin (HCG) - secreted after implantation, what pregnancy tests detect. Stimulates the corpus luteum, increases estrogen and progesterone.
- After first 12 weeks, placenta forms secreting HCG and HCS |
|
|
Term
| What is HcG responsible for? |
|
Definition
- Increase in estrogen and progesterone from the corpus luteum until placenta formed
- Formation of the testes --> Testosterone production
- Increase in estrogen = increase in mother's: uterus, breast's, vagina, fetal development
- Increase in progesterone = endometrial development, prepares breasts for lactation. |
|
|
Term
| What does HCS contribute to? |
|
Definition
| breast development in the mother, decreases insulin sensitivity in the mother. |
|
|
Term
| What is the hormonal effect on birth? |
|
Definition
Progesterone inhibits contractions, drops in 7th month
Estrogen stimulates contractions
Increase in oxytocin and oxytocin receptors. Oxytocin/Pitocin released from posterior pituitary --> contraction of the uterus via IP3/DAG |
|
|
Term
| What prostaglandin analogs can be used to assist in contractions? |
|
Definition
Exogenous prostaglandins aid in cervical ripening and increase in contractions
- PgE2 - Dinoprostone/Cervidil or Prepidil. Locally delivered
- PgE1 - Cytotec/Misoprostol - Off label, DO NOT USE
- PgF2 - Carboprost - uterine contraction |
|
|
Term
| What hormones regulate the breasts post-partum? |
|
Definition
- Estrogen, progesterone, hGH, and GCs inhibit SECRETION of milk but stimulate tissue. Critical in the development of breast tissue.
- Prolactin - secretion of milk into alveoli. Stimulated by sucking, not stored. DA inhibits. DA --> PIH --> no prolactin.
- Oxytocin - milk 'let-down', ejected from alveoli into ducts. Can become conditioned. |
|
|
Term
| What 3 estrogens are present in women? |
|
Definition
- Estradiol - most potent
- Estrone - most common, highest in post-menopausal women
- Estriol - weakest
All 3 are linked, formed from DHEA |
|
|
Term
| What is estrogen bound to in the blood? |
|
Definition
Unlike androgen, estrogen is more bound to albumin than SHBG. once unbound, can penetrate cells. Like androgens, kick off HSP and receptors dimerize.
**Estrogen receptors need a co-activator or co-repressor to work
**alpha or beta co-receptor. |
|
|
Term
| What is the difference between estrogen receptors? |
|
Definition
ERalpha - in the reproductive tract
ERbeta - in the vasculature and prostate |
|
|
Term
| How are estrogens metabolized? |
|
Definition
- Through direct conjugation. Bile is stored in the gall bladder --> intestines and can be RECYCLED. Need gut flora to do this.
- 3A4 metabolism then COMT. Metabolites can be toxic. |
|
|
Term
| How is oral bioavailability of estradiol increased? |
|
Definition
Estrace/estradiol is not very orally bioavailable
Add a -17-ethinyl = ethinyl estradiol --> increased potency and orally available. Why it is dosed in micrograms.
Mestranol is a pro-drug |
|
|
Term
| What are estradiol esters? |
|
Definition
Longer duration of action, form a depo.
- Estradiol valerate/Delestrogen
- Estradiol Cypionate/Depo-estradiol |
|
|
Term
| What is premarin/conjugated estrogens used for? |
|
Definition
Estrone + estrogens from mare's urine, Tx of post-menopausal symptoms.
W/o estrogen, vagina can atrophy |
|
|
Term
| What are adverse effects of estrogen therapy? |
|
Definition
- increased risk for endometrial carcinoma - standard practice to co-adminster progestin
- Combo increases risk for breast cancer
- THROMBOEMBOLISM |
|
|
Term
| What drugs are anti-estrogens and selective estrogen receptor modifiers? |
|
Definition
- Clomid/Clomiphene - an anti-estrogen, prevent estrogen-ER effects
- Tamoxifen/Nolvadex - selective antagonism of ER, used for breast cancer |
|
|
Term
|
Definition
inhibits estradiol binding to ER. Can induce ovulation, mostly works in breast cancer.
**recruits co-repressors in breast or hypothalamus, no transcription. |
|
|
Term
| How does clomiphene work? |
|
Definition
Strong antagonist of both types of ER in all tissues (trans isomer).
Inhibits negative feedback loop of estrogen, inducing ovulation
**tissue perceives low level estrogen --> LH/FSH surge |
|
|
Term
| How does progesterone mediate it's effects? |
|
Definition
Two isoforms of progesterone receptors
- PR-B is the stimulatory effects of progesterone
- PR-A is an inhibitor of PR-B and other steroid hormones
**binding occurs in the cytosol, not the nucleus. |
|
|
Term
| What are the effects of progesterone? |
|
Definition
Primes endometrium for implantation, increases cervical secretions.
- NECESSARY for maintenance of pregnancy
- Development of mammary glands
- Increases lipid profiles like estrogen. Higher doses interfere with milk production. |
|
|
Term
| How are progestins used for pharmacotherapy? |
|
Definition
- Contraception or in combo for hormone therapy
- Pregnanes: progesterone or medroxy-
- Estranes: Norethindrone or Ethynodiol
- Gonanes: Norgestrel or Norgestimate |
|
|
Term
| What is the MoA of oral contraceptives? |
|
Definition
prevent the LH/FSH surge which is dependent on high estrogen. Use the body's own mechanism of keeping estrogen at a low level, exerting a negative feedback and prevents ovulation.
- Progestins diminish the GnRH pulse, decreasing ovulation. |
|
|
Term
| What are adverse effects of oral contraceptives? |
|
Definition
CV: increased thromboembolism! Even with transdermal use.
Estrogen mediated cancers, breast and uterine cancer.
Increase in LDL |
|
|
Term
| How do emergency contraceptives work? |
|
Definition
Within 72 hours.
High dose progestins: Alteration in corpus luteum and endometrium
Partial agonists: Degeneration of endometrium, cannot sustain and implanted egg |
|
|
Term
| What drugs are used to treat endometriosis? |
|
Definition
GnRH agonists:
- Leuprolide/Leupron
- Buserelin/Suprefact
- Nafarelin/Synarel
- Histrelin/Supprelin
- Goserelin/Zoladex
- Deslorelin/Suprelorin
**Also OCs, progestins, aromatase inhibitors. |
|
|
