Pituitary Physiology Flashcards by Emily Prazak

What are the two types of cells in the anterior pituitary?

sommatotrophs

mammotrophs

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What do sommatotrophs secrete?

growth hormone

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What do mammortophs secrete?

prolactin

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For the prolactin axis, what is the stimulation for release of prolactin?

prolactin releasing hormone

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For the prolacitn axis, what is the inhibition against release of prolactin?

prolactin inhibitory hormone = dopamine

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For the growth hormone axis, what is the stimulatory signal for release of GH?

GH releasing hormone?

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What’s the inhibition on the release of GH?

Growth hormone releasing hormone = somatostatin

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What kind of G protein does somatostatin work to inhibit GH release?

a Gi couple receptor to decrease cAMP and activate K+ channels

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What other hormone/neurotransmitter will also inhibit GH release?

dopamine

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Where is the GH releasing hormone receptor located?

on the somatotrophs of the anterior pituitary

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WHat kind of receptor is the GH releasing hormone receptor?

GPCR

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What’s anther name for grwoth hormone?

somatropin

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In serum, what is GH bound to?

growth hormone binding protein

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What is the GHBP really?

it’s the ectodomain (outide the cell membrane) of the GH receptor, which is solubilized, therefore levels of GHBP indicate tissues levels of GH RECEPTOR!

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What ind of secondary messenger signal transduction pathway is activated by activation of the GH receptor?

JAK/STAT signaling

homrone binding causes dimerization and internlalization of the complex

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Target cells for GH are everywhere. What does the liver produce in order to get a special signal from GH?

insulin-like growth factor -1 (somatomedin)

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What does GH promote?

growth of all tisuses thorugh up-regulation of metabolic effects

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Which is more stimulatory for growth in bones: GH or IGF-1?

IGF-1 actually

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GH can be antagonized by what other hormone? Why is this clinically important?

glucocorticoids - stuntin in children treated with cortisol

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In the case of protein metabolism, what does GH do?

increase AA uptake and protein synthesis

retention of nitrogen, phosphorous and potassium

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WHat does growth hormone do to mineral metabolism?

increases muscle density in bones after longitudinal growth ceases and epiphyses have closed.

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What does growth hormone do to carbohydrate metabolism?

carb utilization is uniformly decreased

in a normal individual, GH effects are not after a meal, so it’s not a major modulator of blood glucose. but in cases of fasting, growth hormone is there to help prevent hypoglycemia (which is lethal)

so it promotes hyperglycemia and is thus diabetogenic (reduces tissue uptake of glucose, increases liver production of glucose and then later promotes secondary insulin release)

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What does GH do for fat metabolism?

it increases mobilization of fats for energy

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What tissue releases GH releasing hormone and somatostatin?

hypothalamus

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What does severe GH deficiency in children lead to?

proportional dwarfism (you're proportional, but really short)

What is the syndrome that occurs with autosomal recessive GH receptor that is insensitive to GH?

Laron syndrome

What gene on the X chromosome will cause short stature if lost?

short stature homeobox gene (SHOX) seen in Turner syndrome or with a point-mutation in SHOX

How does nutrition relate to GH?

poor nutrition will decrease GH and stunt growth

What will GH deficiency in adults cause?

generalized boesity reduced muscle mass asthenia (reduced energy) reduced cardiac output

Why are random serum samples not helpful for trying to diagnose GH hyposecretion?

because GH is relased in a pulsatile pattern daily secretion peaks about 2 hours after the onset of deep sleep

So what hormone could you look at to meausre growth hormone?

IGF - because the liver hormone isn't pulsatile and will last for 12-16 hours. so measuring IGF-1 will tell you whether the patient has GH around

How does the insulin tolerance test work?

1. administration of insulin induces hypoglycemia 2. this should stimulate the adrenal glands to secrete cortisol and the pituitary gland to secrete growth hormone 3. failure of an increase in GH may suggest the need for growth hormone replacement

How does the glucagon test work?

basically an indirect insulin test 1. administer glucagon to induce transient hyperglycemia 2. stimualtes subsequent hypoglycemia (via insulin release) 3. this stimulates subsequent growth hormone

What do you give in addition to a GHRH analog in a co-stimulation test?

arginine - induces GH release

What children should you give growth hormone supplementation for?

those with: 1. hypopituitarism 2. idiopathic short stature 3. Turner syndrome growht deficiency 4. Other SHOX mutations 5. Pituitary trauma

WHat measurement will you use to titrate GH doses?

IGF and IGFBP3

Historially, where did we get growht hormone from for supplementaiton?

extraction from dead human pituitaries - don't do anymore because of prion disease transmission

Today, where do we get GH supplementation?

recombinant human growth hormone preparations

What are the negative side effects of growth hormeon supplementation?

antibiotics to the GH develop in 30% - usually of little consequence rapid growth resultin gin scoliosis diabetogenic

What are some other experimental uses for GH?

hypoglycemia, burns, bone marrow hypoplasia, other growth syndromes muscle wasting syndrome associated with AIDS potential for abuse with athletes/body buliding

Will IGF deficiencies be responsive to GH?

nope

What can you give for low IGF?

mecasermin which is just recmbinant IGF-1 mecasermin rinfabate - contains a complex of recominant human IGF-1 and recombinant IGFBP3

What is IGFBP3?

IGF carrier protein - modulates IGF effects

What are the isde effeects of recombinant IGF1?

hypoglycemia | increased cytochrom p450 - reduces duration of drugs metabolized by that system

Who should you NOT give recominant IGF to?

kids with cancer | people who have closed epiphyses

Hypersecretion of GH will result in what during childhood?

gigantism: increased height and prominent jaw, enlarged hands with stubby fingers and feet.

Hypersecretion of GH will reuslt in what during adulthood?

acromegaly

How do we diagnose GH hypersecretion?

elevated IGF-1 confirmed by elevated GH level after glucose administration

What are the general strategies for treatment of hypersecretion of GH?

promote GHIH and dopamine to inhibit GH secreiton

What are two drugs that are used for this?

bromocriptin: DA agonist Octreotide: long-acting somatostatin analog

What drug is a GH receptor antagonist in the liver which is a newer treatment for hypersecretion of GH?

pegvisomant

MOVING TO PROLACTIN

What kinase is activated by prolactin binding?

Janus kinase (which is part of the JAK/STAT dimer family)

What are the two forms of prolactin receptors?

short forms and long forms

What do the short forms do?

soaks up the prolactin and inhibit it's activating the long receptor so it's a negative regulator. so the long form is the one that triggers the signalling

What things are prolactin physiologic effects?

1. immunity and autoimmunity 2. breast development during pregnancy 3. mild secretion during lactation

WHy is lactation inhibited with retained placenta?

placenta secretes high levels of progesteron, which inhibits prolactin

Is prolactin under tonic inhibition or activation by the hypothalamus through dopamine?

tonic inhibition

What dopamine receptor resides on pituitary mammotrophs to enact this inhibition?

D2 receptors

If the pituitary portal system is blocked or severed, what will happen to pituitary prolactin secreiton?

it will increase! Which is unique because all the others will decrease happens because the dopamine can't get to the cells to inhibit release

Prolactin is important for milk production, but what is necesary for milk let down?

oxytocin

What are some causes of prolactin hypersecretion (not associated with pregnancy or lactation)?

1. pituitary tumors secreting prolactin 2. tumors that disrupt the tonic inhibition 3. iatrogenis (dopamine antagonists - antipsychotics) 3. injury, lesion of the hypothalamus or pituitary

What are the therapeutic uses for prolactin?

none yet

WHat does prolactin hypersecretion cause in males?

impotence (suppresses gonadotropin releasing hormone)

What does prolactin hypersecretion cause in females?

amenorrhea (suppression of gonadotropin releasing hormone) galactorrhea infertility

Why is it easy to treat tumors that cause hyperprolactinemia?

many lactotroph pituitary tumors express high levels of D2 receptors, so you can just use dopamine agonists

What drug is preferred to other dopamine agonists because it has higher efficacy in normalizing prolactin levels and a higher frequency of pituitary tumor shrinkage?

Cabergoline

What are the side effects of cabergoline?

nausea, vomiting, dizziness, and orthostatic hypotension