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Anterior Pituitary


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Growth Hormone-Releasing Hormone
Somatostatin; growth hormone inhibiting hormone
Dopamine, PIH
Prolactin-Inhibiting Hormone
TRH + others like VIP
Prolactin-Releasing Factors
Thyrotropin-Releasing Hormone
Corticotropin-Releasing Hormone
Gonadotropin-Releasing Hormone
Why not just have Neurohypophysis arrangement?
Because there isn't a 1-1 arrangement between tropic factors and Anterior Pituitary hormones.
GnRH stimulates/inhibits?
stimulates FSH and LH
GRH stimulates/inhibits?
stimulates Growth Hormone
SS stimulates/inhibits?
inhibits Growth hormone and TSH
TRH stimulates/inhibits?
stimulates TSH and Prolactin
PRF stimulates/inhibits?
stimulates Prolactin
PIH stimulates/inhibits?
inhibits prolactin
CRH stimulates/inhibits?
stimulates ACTH
Why are irregular menstrual cycles one of the hallmark symptoms of hypothyroidsm?
In cases of primary hypothyroidism (not enough thyroid hormone), this will dis-inhibit the hypothalamus (making it more active) which will stimulate TRH, which stimulates TSH release, which stimulates the thyroid to make more hormone and at the same time the TRH will stimulate prolactin release, which will make menstrual cycles irregular, because the hypothalamus uses releasing hormones, it doesn't use the posterior pituitary mechanism.
HPT Hormones are all ____ of varying length, which bind to ______
HPT hormones are all peptides of varying length, which bind to cell surface receptors becaus they are hydrophilic. Therefore, they do not go into the cell to bind to intracellular receptors. Because they are binding to cell surface receptors, they must use Second Messengers.
HPT Hormones act on cell-surface receptors. Precise second messenger mechanisms are obscure, but may involve ___pathways
cAMP, IP3, and DAG
Most peptides will not get into cells, so they must use a ____ mechanism involving second messengers
signal transduction
HPT Hormones are short-lived in circulation for what 2 reasons?
HPT hormones are degraded by _____
general and specific proteases
Dopamine, or PIH, is degraded by ____
catecholamine oxidation pathways
What is pulsatile release?
When a hormone is produced in the hypothaamus, it is not coming out all the time/not continuously released, but instead it is released as a pulse. When the pulse is coming out of the hypothalamus to the pituitary, the hormones bind to a receptor so that a receptor can respond to it. If the hormone is present all the time, then the anterior pituitary cells that are responding it will be sesensitized, they stop responding and their response per amount of releasing hormone goes down.
Advantages of pulsatile release
So the pulsatile release is present t keep the anterior pituitary cells responding at their optimal rate/optimal response. Pulses can also convey information.
Explain how pulses are important in treating prostate cancer.
Prostate cancer is almost always hormone dependent. Prostate cancer is almost always androgen receptor positive. In the absence of androgen, prostate cancer slows its growth rate. If you remove testosterone from the system, you can slow the growth rate of prostate ancer. One of the ways to do this is to provide a GnRH agonsit over time, a little bit is released all the time -> what this does is it desensitizs the pituitary so that it is not making LH which stimulates testosterone production -> so that its not pulsing (released in pulses) like natural GnRH -> produces a lowering of testosterone with a constant (not pulsing) stimulation of the pituitary.
Short-loop feedback control: Inhibitory action of ______ on ____secreting HPT hormone.
Inhibitory action of anterior pituitary hormone on hypothalamic neurons secreting HPT hormone.
Long-loop feedback control: Inhibitory action of ____ on ____secreting HPT hormone.
Inhibitory action of target organ hormone on hypothalamic neurons secreting HPT hormone.
Which endocrine system does not use short loop feedback?
emotions, stress, etc.
CRH (and thereby ACTH) secretion increased in response to "stress"
Outside the individual
Light/Dark rhythms, olfactory signals, signals from our environment.
Why is the pineal gland an endocrine gland?
It produces a hormone (melatonin)
The pineal gland appears to lack direct neural connection with the brain, except via ____
superior cervical ganglion
Pineal gland producs melatonin, a 'hormone' which may be involved in ____
circadian regulation

functions in regulating sleep/wake cycles
Melatonin production increases in response to what?
darkness, hypoglycemia, sympathetic stimulation
What are the three groups of anterior pituitary hormones?
1) Corticotropin-related peptides
2) Somatomammotropins
3) Glycoproteins
What type(s) of cells are corticotropin-related peptides?
What type(s) of cells are somatomammotropins?
Somatotrophs, lactotrophs
What type(s) of cells are glycoproteins?
thyrotrophs, gonadotrophs
Corticotrophs produce what hormones?
Somatotrophs produce what hormones?
Lactotrophs produce what hormones?
Thyrotrophs produce what hormones?
Gonadotrophs produce what hormones?
What cell types are produced in basophilic cells?
corticotrophs, thyrotrophs, gonadotrophs
What cell types are produced in acidophilic cells?
somatotrophs, lactotrophs
ACTH is a fragment of what?
POMC can be proteolytically cleaved into what main 3 fragments?
N-term Fragment, ACTH, B-LPH
What does the N-term fragment play a role in?
Involved in lipid metabolism, growth stimulation of the adrenal cortex, or just a structure role
What does alpha-MSH play a role in?
stimulates melanocytes. In disorders where ACTH is overproduced, you get an interesting pigment in skin folds leading to hyperpigmentation. So MSH does explain disorders due to ACTH overproduction.
What two fragments of ACTH have more function in lower animals than higher organisms?
alpha-MSH, CLIP. These two fragments may explain disorders due to ACTH overproduction
What does B-endorphin play a role in?
endorphin= pain relieving peptides/ short proteins produced in the brain and modulate pain reception
Why would endorphin structure be a part of POMC?
stress, caused by pain, releases ACTH, which has endorphins to reduce pain
ACTH stimulates ____
adrenal cortex
ACTH stimulates adrenal cortex to secrete what 3 things?
1) glucocorticoids
2) Mineralocorticoids (like aldosterone)
3) androgenic steroids
What stimulates ACTH for secretion?
1) CRH from the hypothalamus
2) Stress
Stress comes in what three forms?
1) Physical (highest stress response)
2) Emotional (lowest efficacy for ACTH/CRH production is emotional stress)
3) Chemical
Endogenous cortisol (normal amount) will not blunt stress response, but ____ will suppress
Endogenous cortisol will not blunt stress response, but high dose exogenous corticosteroids will suppress.
ex: triamcinolone & prednisone respress the stress response and tune down the immune system and inflammation
Name two inhibitors of ACTH
Cortisol and ACTH
Cortisol inhibits normal secretion of ACTH by what two mechanisms?
How does the fast mechanism or cortisol inhibit normal secretion of ACTH?
(non-nuclear) --> sensitive to a change in cortisol as a function of time. A rapid rise in cortisol shuts off ACTH production (gene transcription) very quickly because it is too fast to be transcriptionally active.
How does the slow mechanism or cortisol inhibit normal secretion of ACTH?
(nuclear) --> cortisol comes into the cell, binds to a receptor, influences gene transcrition --> what we would expect. It is sensitive to concentration of cortisol
Growth Hormone (GH) is cleaved from what?
GH effects are mediated by what two things?
1) Insulin-like Growth Factor-I (IGF-I)
2) Insluin-like Growth Factor-II (IGF-II)

These do all the growth promoting effects. These both have structures that look a lot like insulin.
Functions of GH?
1) Enhances amino acid uptake and mRNA transcription & translation

2) Mobilization of fat (by stimulating lipolysis) leads to protein sparing for growth

3) In excess: decreases carbohydrate utilization by imparing glucose uptake. GH interrupts insulin binding to glucose transporter.
What physiologic stimuli secretes GH?
sleep, exercise, stress, postprandial hyperaminoacidemia (after a meal, more amino acids in the blood)
What pharmacologic stimuli secretes GH?
GRH, ACTH, ADH, a-agonists, b-antagonists

a-agonists: stimulate effects of epi/norepinephrine

B-antagonists: binds to B-receptors to control BP and arrhythmias
What pathologic stimuli secretes GH?
Starvation, renal failure

Starvation: preserves those proteins, promotes utilization of other nutrients like fat and glucose.
What physiologic secretions inhibit GH?
Postprandial hyperglycemia, Free fatty acids
What pharmacologic secretions inhibit GH?
Somatostatin (antagonist to GHRH), GH (feedback), cortisol, a-antagonist, B-agonists

a-antagonists: blocks the effects of epi/norepinephrine at a-receptors

B-agonists: suppress growth to some degree
What Pathologic secretions inhibit GH?
Obesity, hypo-and hyper-thyroidism
How does hypothyroidism inhibit GH?
If you are hypothyroid, you'll produce a lot of PRH, which to some degree reduces GH release
How does hyperthyroidism inhibit GH?
If you are hyperthyroid, you are burning a lot of nutrients, and you have extra thyroid hormone.
Prolactin is cleaved from what?
Functions of PRL
1) Stimulates postpartum lactation
2) Stimulates breast development in concert with E2 and P during pregnancy
3)Excess PRL feedback- inhibits gonadotropin release, producing hypogonadism, or in womn it is amenorrhea.
Why doesn't a woman produce milk during pregnancy?
Because estrogen suppresses lactation.

PRL increases during pregnancy but its lactogenic effect is suppressed by estrogen; when estrogen falls after parturition, PRL initiates lactation.
What physiologic stimuli secretes PRL?
Pregnancy, nipple stimulation, nursing
What pharmacologic stimuli secretes PRL?
TRH, estrogen, dopamine antagonists
What pathologic stimuli secretes PRL?
Prolactinomas, lesions of pituitary stalk, liver/kidney disease; hypothyroidsm
How does hypothyroidism secrete PRL?
If you are hypothyroid, little thyroid hormone is being released, which means that this will be a stimulus for TRH release. And since TH also stimulates prolactin, extra prolactin will be produced.
How do dopamine antagonists stimulate secretion of PRL?
If you antagonize dopamine receptors, then you will have more prolactin release.

Dopamine is the prolactin inhibitory hormone (PIH). So if you antagonize the receptor effects of dopamine, you will increase prolactin release -> secreting more PRL
What pharmacologic secretions inhibit PRL?
dopamine (PIH) & Dopamine agonists
Give an example of a dopamine agonist

It is useful therapeutically. Bromocriptine was historically used to suppress production/lactation in women who gave birth to stillborns (dead at birth) in the immediate postpartum (after childbirth) period. In this circumstance, it could be stressful for women to produce milk w/out needing to breastfeed.
What pathology inhibits PRL?
pituitary removal or destruction
TSH (thyroid stimulating hormone) is also called?
Thyrotropin is a small protein with what two subunits?
alpha is similar to what other kind of hormone?
similar to other glycoprotein hormones (LH, FSH, HCG
beta is ____ in each of these hormones, so confers biologic specificity
So alpha and beta subunits are secreted together but ____
not covalently bound
Functions of TSH
1) Stimulates iodide uptake into thyroid gland
2) stimulates synthesis & release from storage of T4 and T3 (acts via adenylyl cyclase/cAMP)
3) induces increase in thyroid gland size
How do you get goiter?
If you do not have a lot of iodine in your diet, T4 levels go down. When this happens, TRH goes up. Increases TSH release. Thyroid gland increaes in size -> Goiter
What physiologic stimuli secrete TSH?
Temperature (low temperatures tend to increase TSH)

insulin-induced hypoglycemia
What pharmacologic stimuli secretes TSH?
1) TRH (the ability of T3 to regulate the sensitivity of TRH)

2) reduced thyroid hormones (TSH increases because of a lowering of the thyroid hormones T3 and T4)

3) estrogens
What pathologic stimuli secretes TSH?
TSH-secreting tumors
If pregnancy is unknown, why can it look like hyperthyroidism in women?
Women tend to have slightly higher TSH levels than men. In pregnancy, the levels of estrogen rise, and so there will be more synthesis of TSH and high T3 and T4. If pregnancy is unknown, it can look like hyperthyroidism.
What are the pharmacologic inhibitors of TSH?
1) increased T3 &/or T4
2) somatostatin, dopamine (and dopamine agonists), glucocorticoids, growth hormone all negatively interact
What are the pathologic inhibitors of TSH?
acute or chronic disease, tumors of anterior pituitary or hypothalamus
increase TSH, ____T3/T4
decrease TSH, ____T3/T4

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