Endocrine System (Growth Hormone) Flashcards by Jeff Lattman

The major functions of the body are regulated by the nervous and endocrine system which are linked by?

Hypothalamus/pituitary and adrenal medulla

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Define endocrinology

Analyzes formation of hormones, site of production and mechanisms of action

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What are the two classes that hormones are typically divided into?
What do they do? Examples?

Hormones that act via nuclear receptors to modulate transcription (steroid, thyroid, vitamin D and vitamin A, and via membrane receptors to exert rapid effects on signal transduction pathways (peptide and amino acid hormones)

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Three classes of hypothalamus hormones?

Produced in hypothalamus and released in the pars nervosa
Stimulating or inhibiting hormones produced by hypothalamus
Hormones produced in the pars distalis

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anterior pituitary (AP) hormone:
Growth Hormone:
hypothalamic releasing factor(s)?
AP cell type?
systemic effects?

growth hormone releasing hormone (GHRH) (+) and somatostatin (-)
somatotropes
growth promotion, gluconeogenesis

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anterior pituitary (AP) hormone:
Prolactin:
hypothalamic releasing factor(s)?
AP cell type?
systemic effects?

Suckling (+) and Dopamine (-)
Lactotropes
stimulate lactation, induce milk proteins

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anterior pituitary (AP) hormone:
Thyroid-stimulating hormone:
hypothalamic releasing factor(s)?
AP cell type?
systemic effects?

thyrotropin-releasing hormone (TRH)
thyrotropes
stimulate thyroid gland to synthesize T4 and T3. increase size and secretion of thyroid gland

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anterior pituitary (AP) hormone:
Adrenocorticotropic hormone:
hypothalamic releasing factor(s)?
AP cell type?
systemic effects?

corticotropin-releasing hormone (CRH)
corticotropes
cortisol secretion (to adrenal cortex)

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Which AP hormone is a POMC-derived hormone?
a. Corticotropin
b. Follicle-stimulating hormone
c. Prolactin
d. TSH

a. Corticotropin

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Which AP hormone is a POMC-derived hormone?
a. hCG
b. LH
c. a-Melanocyte SH
d. EGF

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Which AP hormone is a somatotropic hormone?
a. a-Melanocyte SH
b. EGF
c. HGF
d. Prolactin

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Which AP hormone is a human chorionic somatomammotropin (HCS) hormone?
a. TSH
b. Placental lactogen
c. HCG
d. FSH

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From the list: Identify the Glycoprotein hormones:
1. Luteinizing hormone
2. Corticotropin
3. EGF
4. FSH
5. TSH
6. Lactogen
7. Prolactin
8. hCG
9. HGH
10. EGFR

1, 4,5,8

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T/F GH and PRL can stimulate each other’s corresponding receptor

False: GH can activate PRL-R, but PRL cannot activated GH-R

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what is the relationship between GH and insulin-like growth factors (IGF)?

GH stimulates release of IGF-1 and -2 from liver which help with several of the growth-promoting effects of GH

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GHRH release from hypothalamus is __________
Somatostatin release from hypothalamus is ______
Growth hormone release is _________

constant, pulsatile, pulsatile

Ghrelin’s effect on:
growth hormone?
somatostatin?
GHRH?

stimulate
inhibit
stimulate

somatostatin’s effect on:
GH?
GHRH?

inhibit
inhibit

IGF-1’s effect on:
GH?
GHRH?

inhibit
inhibit

GH is secreted as a heterogeneous mixture of peptides; the principal form is a single polypeptide chain of _________.
Alternative splicing produces a smaller form of ______ (~20) with equal bioactivity that makes up 5-10% of _________.
_____ consists of the ______ form only, providing a way to detect ___________.
In the circulation, a ______ protein, which is derived from the extracellular domain of the _________________, binds and transports GH
Bound GH has a biological t1/2 about __ times that of unbound GH.
Bound GH may provide a __________ that dampens acute fluctuations in GH levels associated with its pulsatile secretion

22 kDa
kDa, circulating GH
rGH, 22 kDa, GH abuse
55 kDa, proteolytically cleaved GH receptor
10
GH reservoir

Which of the following does NOT promote tissue growth?
a. IGF-1
b. IGF-2
c. Ghrelin
d. GH

Insulin receptor a2b2 tetramer has what what important activity?
GH receptor does/does not have the same activity?

intrinsic tyrosine kinase activity
does not

Binding of GH to GHR results in the activation of JAKs, what does JAKs do?

phosphorylates STAT proteins which go into nucleus and regulate gene expression

although GH does not have intrinsic tyrosine kinase activity, how does it indirectly activate tyrosine kinase?

when GH binds to GHR, JAK2 can bind to GHR which is a cytoplasmic tyrosine kinase of the Janus kinase family

JAK2 binds to GFR and causes tyrosine phosphorylation to mediate downstream signaling such as ______ which activates expression of _____ Negative feedback: GH, through ______, induces expression of a family of _______________ proteins and a group of tyrosine phosphatases that disrupt the communication of the activated ______ with _____

STAT5, IGF-1 STAT5, suppressor of cytokine signaling (SOCS), GHR, JAK2

Growth hormone: longitudinal growth of ______ is most striking physiological effect. increases ____________ after the epiphyses have closed. increases __________, _________ and ___________. has potent anti-_____ actions in both the liver and peripheral tissues that decrease _______ utilization and increase _________. most of the anabolic and growth-promoting effects of GH are mediated indirectly through the induction of ______ and ______. ______ and _____ belong to the cytokine and receptor tyrosine kinase superfamily, respectively. loss-of-function mutations in both alleles of the ______ gene results in severe intrauterine and postnatal _________ that is unresponsive to GH, but responsive to _____

bones bone mineral density muscle mass, kidney size, GFR of kidney insulin, glucose, lipolysis IGF-1, IGF-2 GHRs, IGF-1Rs IGF1, growth retardation, IGF1

Pegvisomant, a variant of GH, causes GHR internalization but cannot trigger the conformational change that stimulates _______________

downstream events

Excess production of GH: syndromes of excess secretion of GH typically are caused by _______ that oversecrete GH. Clinical Manifestations of Excess GH: if the epiphyses are unfused, GH excess causes increased longitudinal growth, resulting in _______. GH excess in adults causes _______ (describe it). Mortality is _______. Tumor also causes compression of and injury to __________, ____________ and ______________. Other problems may include ____, ____ and increased risk of ________

somatotrope adenomas gigantism acromegaly: flat-bone growth, causes enlargement of the face, hands, and feet. increased pituitary gland, optic nerves, optic chasm HTN, DM, colon cancer

Diagnosis of Growth Hormone Excess: Gigantism/acromegaly should be suspected in pts with the appropriate signs/symptoms, diagnostic confirmation requires demonstration of increased circulating ________ or ____. Another diagnostic test for both conditions is the _________ (describe test)

GH, IGF-1 oral glucose tolerance test: normal ppl suppress GH level to less than 1 ng/mL

Treatment of GH Excess: initial treatment of gigantism/acromegaly is selective _____ of the _______. radiation and drugs that _____________ are given if surgery does not cure. Pituitary irradiation may be associated with long-term complications, including ______________ and __________. Thus, increases attention has been given to pharm management of acromegaly

removal, adenoma inhibit GH secretion visual deterioration, pituitary dysfunction

We use somatostatin analogues (usually for acromegaly). The goal of treatment is to decrease GH levels to less than _______ after an ____________ and to bring ____ levels to within normal range Synthetic SST agonist analogues are selective for which SST receptors?

2.5 ng/mL, oral glucose tolerance test, IGF1 SST2 and SST5

SST Analogue: Ocreotide (Sandostatin): Administration? Effect?

Ocreotide: subQ TID Ocreotide LARIM: once every 4 weeks decreases tumor size while pt stays on med

SST Analogue: Lanreotide (Somatuline): Administration? Effect?

subQ every 4 weeks prolonged suppression of GH secretion

SST Analogue: Pasireotide LAR (Signafor): Use?

Cushing disease

SST Analogue: Vapreotide (Sanvar): Use?

treating esophageal variceal hemorrhage pts with portal hypertension

Adverse effect of SST analogs: GI: CV: Endocrine:

GI: diarrhea, nausea, and abdominal pain: very common, lessen over time. May develop tiny gallstones\ CV: bradycardia and QT prolongation Endocrine: -inhibit TSH secretion -Pasireotide can cause hypocortisolism -decrease insulin secretion, but reduce insulin resistance

GH deficiency: Children with GH deficiency present with _____, ______, and a __________. GH deficiency in adults is associated with increased _______, decreased ___________ and _______ with reduced _______ and ______, with an increased mortality from _______________

short stature, delayed bone age, low age-adjusted growth velocity body fat, muscle, bone mass, strength, endurance, CV causes

GH is listed as a prohibited class ____ substance