Flashcards in Pituitary Physiology (5/15) Deck (60)
Describe post pit development
The posterior pituitary (neurohypophysis) develops as an evagination of the ventral hypothalamus. From neural crest cells.
Describe ant pit dev
The anterior pituitary (adenohypophysis) is formed from evagination of pharyngeal ectoderm, which initially forms a duct called Rathke’s pouch and later fills in and closes. Develops over weeks 5-20
What TFs guide cellular differentiation during dev
Transcription factors that guide this process include Prop-1 and Pit-1. Inactivating mutations in these transcription factors will cause deficiencies in pituitary hormones.
List the 5 ant pit cell types
What does somatotrope produce?
Growth hormone (GH)
What does thryrotrope produce?
What does lactotrope produce?
What does gonadotrope produce?
LH and FSH
What does corticotrope produce?
What are the 3 main groups of ant pit hormones?
1. Glycoprotein hormones (TSH, LH, FSH, share alpha unit)
2. ACTH (comes from POMC)
3. GH and Prolactin (struc homology, can both activate prolactin receptor)
What does LH do?
Stimulates production and secretion of testosterone, preps uterus for implantation of fertilized ovum, stimulates ovulation
What does FSH do?
Stimulates egg and sperm production, stim estrogen synthesis
What does TSH do?
Stim secretion of thyroid hormones by thyroid gland and regulates thyroid cell proliferation and survival
What does ACTH do?
Stim synthesis and secretion of cortisol/adrenal cortex steroids by cortex of adrenal gland and proliferation and survival of adrenal cortex cells
No ACTH: atrophic adrenals
XS ACTH: hypertrophic adrenals
What does prolactin do?
Initiates milk production
What does human growth hormone do?
Stim growth and other effects post natally. Stimulates secretion of IGF-1 from the liver and other organs which is responsible for GH's anabolic effects. Stimulates lipid and CHO metabolism
Which hormones have the same alpha subunit?
TSH, LH, FSH
What does loss of feedback regulation cause?
Pituitary trophic hormone hypersec and hyperplasia of pit cells like in severe hypothyroidism or hypoadrenalism
How do hypothalamic hormones get to the anterior pituitary?
Via the hypothalamic-pituitary portal system
Note: the portal system has two consecutive capillary beds. First carries hormones to the ant pit and does not reach the systemic circulation. Second carries hormones away from the ant pit and reaches systemic circulation
What are two rhythms in endocrinology?
Circadian (daily), most common
Ultradian (bursts, like GnRH)
Hypothyroidism caused by thyroid gland destruction can lead to hypertrophy of which gland?
Anterior pituitary...loss of negative feedback regulation
Describe CRH/ACTH system
Hypothal-->CRH (neg to hypothal)-->ant pit-->ACTH (neg on ant pit and hypothal)-->adrenal gland-->Cortisol (neg on ant pit and hypothal)
What are the extraadrenal actions of ACTH?
Stimulate lipolysis and inc skin pigmentation
What stimulates ACTH release?
CRH, stress, hypoglycemia, anxiety, depression, alpha and beta adrenergic agonists
What pattern does ACTH get released normally?
Diurnal: peaks just before awakening with pulsatility
What inhibits ACTH?
To look for a deficiency in ACTH, when would you measure it?
Highest in the morning normally, measure then to see if its low
To look for excess in ACTH, when would you measure it?
Lowest at night normally, measure to see if its high
How do we measure hypothalamic hormones in the blood?
We don't ! It doesn't get to the systemic circulation
Someone wakes up stressed at 1am, what is their cortisol profile?
High ACTH and cortisol
Someone is sleeping at 1am, what is their cortisol profile?
Lower ACTH and Cortisol
Describe the growth hormone feedback loop
Hypothal-->GHRH (inhib hypothal) and Somatostatin (inhibits ant pit and hypothal)-->ant pit-->GH-->Liver-->IGF1 (inhibits ant pit and hypothal)
What is GHRH
Stimulatory hypothalamic hormone that is stim for somatotropes
What kind of rhythm is GHRH released in?
What is GHRH release stimulated by/
Hypoglycemia, dietary protein, exercise
What is GHRH inhibited by?
IGF1 and GH
Is somatostatin confined to ant pit?
No also has receptors elsewhere like GI and pancreas, hypothalamus
What does somatostatin do?
Opposes GHRH action-inhibits GH release. Also inhibits TSH, PRL in pit and glucagon/insulin in panc
What somatostatin analogs are FDA approved?
Octreotide and Lantreotide
What is GH's rhythm and half life?
Pulatilie with a short half life of 6-20 min
What regulates the amplitude and freq of GH release
Age, gender, nutrition, sleep, body composition, stress, exercise
What does GH stimulate and how?
Stimulates post natal growth via indirect effects of IGF1
If you suspect excessive production of GH. What lab measurement would you order 1st
What physiologic process will lead to decrease in GH production?
-reduction in GHRH secretion
-Inc in somatostatin
-Inc in IGF1
What inhibits prolactin?
Dopamine and dopamine agonists
Waht does prolactin do?
Negatively regulates LH and FSH via hypothalamus (GnRH) and stimulates milk production
Describe the prolactin axis
Hypothal-->PRFs, dopamine (neg to ant pit)-->ant pit-->Prl (neg to hypothal)-->mammary gland
Also stimulating to ant pit is E2 from the ovary
Neural stimulus also goes from mammary gland to hypothalamus
What hormone does prolactin stimulate?
NONE, does not stimulate a hormone and not a subject to feedback
What stimulates prolactin?
Breast stimulation, stress, estrogen, sleep, dopamine antag, TRH
Where is prolactin secreted from?
What physiologic process can explain amenorrhea in a nursing woman?
High prolactin negatively regulates hypothalamic pituitary gonadal axis
What is more impt the concentration or pulsatility of GnRH?
Pulsatility and pulse freq are critical with greater freq and amplitude in puberty
Pulsatile infusion stim LH and FSH sec
Constant infusion inhibits LH and FSH sec to suppress gonadal fxn
What does high FSH, high LH, and low estrogen signal?
What does TRH do?
Stim release of TSH and prolactin
What does TSH do?
TSH stimulates the conversion of T4-->T3. Responsive to intracellular T3 levels, when T3 is high, TRH receptors dec and thus response of thyrotrope to TRH decreases and thus TSH decreases
Describe the thyroid axis
Hypothal--> somatostatin (neg to ant pit) and TRH-->Ant pit-->TSH--->T4->T3 (neg regulate ant pit and hypothal)
What lab changes are expected when there is excessive production of TH (thyroxin) by overactive thyroid gland?
Low TSH, high thyroxin
What is the only axis in which the hypothalamus is primarily inhibitory?
Prolactin regulation by hypothalamus is primarily inhibitory
What are the two inhibitory hypothalamic factors?
Somatostatin and dopamine