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Endocrine
1: physiology of the anterior lobe of the pituitary gland & hypopituitarism
60
Medical
Graduate
01/21/2008

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Term
How much does the pituitary gland weigh and what is the name of the skull depression within which it is located?
Definition
in the adult it weighs, 600mg; sella turcica ("Turkish Saddle");
Term
what are the different parts of the adenohypophysis?
Definition
The adenohypophysis is further divided into the main pars distalis (most distal to the hypothalamus), pars tuberalis (extension of the glandular tissue up the infundibular stalk) and pars intermedia (along the fold line remnant of Rathke’s pouch).
Term
what are the different parts of the neurohypophysis?
Definition
The posterior lobe (neurohypophysis) is composed of the axons of hypothalamic neurons that extend downward as a large bundle behind the anterior pituitary. The neurohypophysis is also divided into the main pars nervosa and the infundibulum. The pituitary stalk or infundibulum connects the pituitary gland with the hypothalamus.
Term
what are the embryological origins of the hypophysis?
Definition
The two lobes have different embryological origins. The anterior lobe is derived from an out pocketing (Rathke’s pouch) of the floor of primitive oral cavity ectoderm. The posterior lobe is an out pocketing from the diencephalon neuroectoderm. Remnants of Rathke’s pouch (Rathke’s pouch cysts) can often be found as cystic cavities sandwiched between the adenohypophysis and neurohypophysis.
Term
what borders the pituitary?
Definition
The pituitary gland is bordered inferiorly by the sella turcica, which is a depression in the sphenoid bone, and superiorly by a tough dural covering, the diaphragm sella through which passes the infundibulum. The cavernous sinuses form the lateral borders of the pituitary. Cranial nerves 3, 4, and 5 pass through the cavernous sinuses. The optic chiasm also runs superiorly to the pituitary. Growth of the pituitary laterally can cause cranial nerve palsies or growth upward can cause visual compromise, most notably loss of vision in the temporal field.
Term
what artery supplies the anterior pituitary?
Definition
A branch of the superior hypophyseal artery -> capillary bed in the lower hypothalamus (median eminence), and hypothalmic hormones destined for the anterior pituitary are secreted into that capillary blood -> hypothalamic-hypophyseal portal veins-> capillaries within the anterior pituitary carry hormones secreted by that gland, coalesce into veins (cavernous sinus veins) that drain into the systemic venous blood.
Term
what provides the major blood supply for the posterior pituitary?
Definition
inferior hypophysial arteries.
Term
what are six major hormones synthesized and secreted by the anterior pituitary?
Definition
polypeptides: GH, PRL, ACTH; Dimeric glycoproteins: TSH, FSH, LH.
Term
in the anterior pituitary Somatotrophs produce
Definition
GH; they compose 50% of cells.
Term
Lactotrophs  produce
Definition
PRL; and compose about 15% of cells
Term
Individual cells within the anterior pituitary secrete a single hormone except
Definition
gonadotropes , in which one cell produces FSH and LH
Term
what are direct effects of GH?
Definition
stimulates adipocytes to break down triglyceride and suppresses their ability to take up and accumulate circulating lipids.
Term
The indirect effects of GH are mediated by what?
Definition
IGF, which mediates the majority of the growth promoting effects of GH.
Term
what stimuates proliferations of chondrocytes and what stimulates their differentiation?
Definition
IGF-1 stimulates proliferation of chondrocytes (cartilage cells), resulting in bone growth. Growth hormone does seem to have a direct effect on bone growth in stimulating differentiation of chondrocytes.
Term
what stimulates both the differentiation and proliferation of myoblasts?  It also stimulates amino acid uptake and protein synthesis in muscle and other tissues
Definition
IGF-1
Term
what are the effects of GH on protein, lipid, and carb metabolism?
Definition

protein - anabolism: amino acid uptake, increased protein synthesis and decreased oxidation of proteins.

fat - enhances the utilization of fat by stimulating triglyceride breakdown and oxidation in adipocytes.

carbs - maintain blood glucose within a normal range, has anti-insulin activity - because it supresses the abilities of insulin to stimulate uptake of glucose in peripheral tissues and enhance glucose synthesis in the liver. Somewhat paradoxically, administration of growth hormone stimulates insulin secretion, leading to hyperinsulinemia.  

 

Term
what is a hypothalamic peptide that stimulates both the synthesis and secretion of growth hormone?
Definition
GHRH
Term
what is a peptide produced by several tissues in the body including the hypothalamus, inhibits growth hormone release in response to GHRH and to other stimulatory factors such as low blood glucose concentration?
Definition
Somatostatin
Term
what is a peptide hormone secreted from the stomach. Ghrelin binds to receptors on somatotrophs and stimulates secretion of growth hormone?
Definition
Ghrelin
Term
how does negative feedback loop work to control GH secretion?
Definition

0. normally GHRH->GH->IGH-1

1. excess GH probably feeds back @ somatotroph to inhibit secretion of GH & @ hypothalamus to inhibit release of GHRH.

2. High blood levels of IGF-1 lead to decreased secretion of growth hormone not only by directly suppressing the somatotroph, but by stimulating release of somatostatin from the hypothalamus.  

Term
what are 6 facts about GH secretion and levels?
Definition
  1. pulsatile pattern
  2. basal concentrations in blood very lo.
  3. frequency & amplitude higher in sleep than waking.
  4. increases during puberty & declines in middle age.
  5. increased by stress & exercise
  6. lower in obese subjects than lean subjects.
Term
How is GH deficiency different in children than in adults? What is used in treating either?
Definition

GH deficiency in children results in short stature and subnormal growth rate. GH deficiency in adults produces increased fat mass, decreased muscle mass, decreased exercise capacity and muscle strength, osteopenia, decreased quality of life (social isolation, fatigue, depression), and elevated cholesterol.

 

Recombinant hGH is approved for treating GH-deficient children and adults.    

Term
Why are random GH measurements not diagnostic of GH deficiency?
Definition
because GH secretion is pulsatile.
Term
what is used to diagnose GH deficiency in children?
Definition
IGF-1 levels are used to diagnose GH deficiency in children but are less helpful in adults because the normal elderly have low values as well.
Term
Why should patients with childhood onset isolated GH deficiency be retested in adulthood before continuing adult GH replacement?
Definition
because isolated GH deficiency during adolescence is often transient and normalization of GH responses are seen in 25-50% of cases.
Term
What defines a GH deficiency?
Definition
lack of increase of plasma GH to 5 ng/ml on two pharmacological stimulation tests.
Term
How many amino acids make up GH?
Definition

you gotta b kidding, right?

190. 

Term
  1. How many amino acids make up Prolactin?
  2. What is the critical cell specific factor that activates PRL gene transcription?
  3. Is PRL secreted in bursts that increase in frequency and amplitude with sleep? 
Definition
  1. 199.
  2. Pit-1
  3. Yes 
Term
what stimulates prolactin release?
Definition
Stimulation of the nipples and mammary gland.
Term
What the two roles of prolactin in milk production?
Definition
  1. Induction of  lobuloalveolar growth of the mammary gland. Alveoli are the clusters of cells in the mammary gland that actually secrete milk.
  2. Stimulation  of milk production after giving birth. Prolactin, along with cortisol and insulin, act together to stimulate transcription of the genes that encode milk proteins.
Term
  1. Unlike the rest of the hormones, what is the one hormone released by the pituitary that is under tonic inhibition?
  2. What is the predominant Prolactin inhibitory factor produced by the hypothalamus?
Definition
  1. Prolactin, of course.
  2. Dopamine. 
Term
What 3 hormones that positively regulate the release of prolactin?
Definition
  1. TRH
  2. VIP
  3. Estrogen 
Term
What are the effects of hyperprolactinemia on women & men?
Definition

Women: amenorrhea (lack of menstrual cycles) and galactorrhea (excessive or spontaneous secretion of milk).

Men with hyperprolactinemia typically show hypogonadism, with decreased sex drive, decreased sperm production and impotence.

Term
a mutation in the Pit-1 gene results in what?
Definition
Congenital PRL deficiency, which also includes deficiencies in GH & TSH.
Term
What polypeptide hormone is the smallest of the three produced in the anterior pituitary?
Definition
ACTH, a 39 amino acid peptide.
Term
what stimulates and inhibits ACTH secretion?
Definition
CRH stimulates ACTH release. Stress in turn stimulates release of CRH. Glucocorticoids (cortisol) eventually released by the adrenal negatively feeds back to inhibit CRH & ACTH release.
Term
A large precursor protein named proopiomelanocortin (POMC) is synthesized and proteolytically cleaved into several fragments.  The hormones other than ACTH that are produced in this process are:
Definition
  • Beta-endorphin and Met-enkephalin: Opioid peptides with pain-alleviation and euphoric effects.
  • Melanocyte-stimulating hormone (MSH): Controls melanin pigmentation in the skin of most vertebrates.
Term
When is ACTH production highest, when is it lowest?
Definition
4:00 am highest, lowest at midnight.
Term
what are the signs of ACTH deficiency?
Definition
Common symptoms are fatigue, muscle weakness, anorexia and weight loss.
Hyponatremia and hypoglycemia may be present, but severe dehydration and hyperkalemia do not occur.
Term
How is ACTH deficiency diagnosed?
Definition
  • A low random serum cortisol level must be confirmed with an ACTH stimulation test unless the value exceeds 18 ug/dl excludes ACTH deficiency.
  • ACTH stimulation test (250 ug) (Cortrosyn test) Subnormal response  is a cortisol level < 18 ug/dl
  • ACTH levels helpful to distinguished primary vs. secondary.
Term

True or False:

The alpha subunit of TSH is also present in two other pituitary glycoprotein hormones, FSH and LH, and, in primates, in the placental hormone chorionic gonadotropin. Each of these hormones also has a unique beta subunit, which provides receptor specificity. In other words, TSH is composed of alpha subunit bound to the TSH beta subunit, and TSH associates only with its own receptor. Free alpha and beta subunits have essentially no biological activity.

 

Definition
True.
Term
What inhibits secretion of TSH  & TRH?
Definition
Secretion of TRH, and hence, TSH, is inhibited by high blood levels of thyroid hormones (T3 + T4) in a classical negative feedback loop.
Term
How is TSH a marker of thyroid disease?
Definition
In disorders of the thyroid producing hypothyroidism, the production of TSH rises, and in hyperthyroidism from thyroid disease (e.g. Grave’s Disease) TSH is suppressed.
Term
What is the diurnal variation of TSH secretion?
Definition
TSH is secreted in a circadian pattern with peak levels between 9 PM and 5 AM.
Term
What is secondary hypothyroidism and how is it diagnosed?
Definition
  • Hypothyroidism occurs with TSH deficiency.
  • Lack of energy, weight gain, cold intolerance and constipation may occur but are usually less severe than in primary hypothyroidism.
  •  
  • Diagnosis is made with a low free thyroxine and normal or low TSH.    
  • Note that the TSH alone cannot be used as a screening test for TSH deficiency.
Term
What is the effect of LH hormone in both males and females?
Definition
In both sexes, LH stimulates secretion of sex steroids from the gonads. In the testes, LH binds to receptors on Leydig cells, stimulating synthesis and secretion of testosterone. Theca cells in the ovary respond to LH stimulation by secretion of testosterone, which is converted into estrogen by adjacent granulosa cells.
Term
What are the effects of LH & FSH?
Definition
in females LH is responsible for formation and continued development and function of corpora lutea.  FSH is stimulates the maturation of ovarian follicles. it also induces superovulatoin - development of more than the normal number of gametes. it supports the function of Sertoli cells, which in turn support many aspects of sperm cell maturation.
Term
What is a ten amino acid peptide that is synthesized and secreted from hypothalamic neurons and binds to receptors on gonadotrophs?
Definition
GnRH
Term

True or False:

 

GnRH stimultes secretion of LH, which in turn stimulates gonadal secretion of the sex steroids testosterone, estrogen and progesterone. In a classical negative feedback loop, sex steroids inhibit secretion of GnRH and also appear to have direct negative effects on gonadotrophs.
 

Definition
True.
Term

True or False:

 

The regulatory loop for LH leads to pulsatile secretion, to a much lesser extent, FSH. The number of pulses of GnRH and LH varies from a few per day to one or more per hour. In females, pulse frequency is clearly related to stage of the cycle.  

Definition
True
Term
the gonads secrete at least two  hormones which selectively inhibit and activate FSH secretion from the pituitary. what are they?
Definition
inhibin and activin, respectively.
Term
what does diminished secretion of LH and FSH cause?
Definition
Diminished secretion of LH or FSH can result in failure of gonadal function (hypogonadism). This condition is typically manifest in males as failure in production of normal numbers of sperm. In females, cessation of reproductive cycles is commonly observed.
Term

True or False:

 

Elevated blood levels of gonadotropins usually reflect lack of steroid negative feedback. Removal of the gonads from either males or females, as is commonly done to animals, leads to persistent elevation in LH and FSH. In humans, excessive secretion of FSH and/or LH is most commonly the result of gonadal failure.  

Definition
True.
Term
How do oral contraceptives work?
Definition
Oral contraceptive pills contain a progestin (progesterone-mimicking compound), usually combined with an estrogen. Progesterone and estrogen inhibit LH secretion, and oral contraceptives are effective because they inhibit the LH surge that induces ovulation.
Term
How is orchidectomy or oophorectomy induced without surgery?
Definition
By administering long acting GnRH analogs, such as leuprolide, which down-regulate LH and FSH synthesis and secretion. No LH/FSH, no ovulations or spermatogenesis.
Term
True or False:

 Fertility can also be stimulated in men and women with hypopituitarism with recombinant pituitary hormones. HCG is used as an LH-like molecule because it has a long half-life whereas the half-life of LH is only 20-30 min.
 
Definition
True.
Term
What is Kallmann's Syndrome?
Definition
An X-linked form of Isolated Hypogonadotropic Hypogonadism (IHH) which is thought to be due to a mutation in a neural cell adhesion protein which guides axon growth and allows GnRH neurons to migrate from their site of origin in the cribriform plate to the anterior hypothalamus. Anosmia (inability to smell) and low plasma levels of LH and testosterone.Because GnRH neurons are not in their appropriate anatomical location, axons to the anterior pituitary do not develop.
Term
In multitropic failure, what is the common sequence of hormone loss?
Definition
  • In multitropic failure a common sequence of hormone loss is GH, LH/FSH, TSH, ACTH and PRL.
  • Prolactin is often increased from compression of the pituitary stalk and interruption of dopamine, which normally inhibits prolactin.  
Term
What are 4 rules to management of hypothyrodism?
Definition
  1. replacing target gland products is easier than replacing pituitary peptide hormones;
  2. if multiple deficits exist, start replacing cortisol first, followed by thyroxine (allows a normal environment for ADH and sex steroids, thyroid accelerates the catabolism of cortisol); and
  3. avoid over replacement, which can contribute to morbidity and excess mortality.
  4. Mineralocorticoids need no supplementation.
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