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Physiology > Growth Hormone & Somatomedin > Flashcards

Growth Hormone & Somatomedin Flashcards

1
Q

Somatotrophs comprise ~ _% of the hormone-producing cells of the anterior pituitary

A

50%

Secretes growth hormone

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2
Q

Major physiological effects of GH

A

Stimulation of postnatal somatic growth & development

Modulation of metabolism in adults

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3
Q

Regulation of GH pulsatile secretion

A
  • Hypothalamic hormones:
    • Growth hormone-releasing hormone (GHRH)
      • ​Stimulates adenylyl cyclase and increases intracellular cAMP & Ca2+
    • Somatostatin / Somatotropin release-inhibiting factor (SRIF) inhibits
  • ​IGF-1 / Somatomedin C
    • ​ inhibits GHRH
    • stimulates somatostatin
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4
Q

Growth hormone therapy

A

higher mortality rate and higher risk of tumors

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5
Q

The phospholipase C/ DAG/ IP3 and PKC pathways regulat eGH secretion how?

A

Increasing Ca2+

Activating PKC

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6
Q

What hormones upregulate GH?

A
  • Stress, sleep, aa-rich meal –> hypothalamic GHRH release
    • Short-term:
      • Increases cAMP, Ca2+, and IP3
      • Increases somatotroph’s GH release
    • Long-term: increase GH transcription via Pit-1
  • ​Thyroid hormone & cortisol synergistically enhance transcription
  • Estrogen & testosterone mildly increase GH transription & synthesis in young adults
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7
Q

Downregulation of GH synthesis & transcription

A
  • GH & somatomedin induces somatostatin –> inhibit GH release
    • Somatostatin binds its own receptor to inhibit GH secretion by decreasing cAMP and Ca2+
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8
Q

Describe the biological action of GH

A
  • Anabolic & diabetogenic.
  • Mediated directly AND indirectly through GH-stimulated production of IGF-1 by the liver and local nonliverproduction
  • IGF-1 –> linear growth, organ size, lean body mass
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9
Q

What impact does fasting have on GH & IGF-1?

A

Increase in GH (anabolic) will promote lipolysis because we now want to conserve glucose for essential tissue (e.g. brain) –> burn fat

Decrase glucose uptake by the muscle

Increase gluconeogenesis by liver

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10
Q

When do GH level peak in fetal serum?

Do premature of full-term infants have higher serum GH?

When does GH peak in the lifetime?

A

20th wk of gestation

Premature infants have higher GH

Amt of GH secreted is greatest during adolescence, then decreases with age

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11
Q

Somatostatin

aka

GH-inhibiting hormone

A

Hypothalamic peptide that diminishes the frq and amplitude of GHRH pulses

Does this by acting through its own membrane receptor –> decrease intracellular Ca2+ and cAMP

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12
Q

GH release pattern is also influenced by

A
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13
Q

What stimulates somatostatin (GHIH)?

A

Hyperglycemia

High FA

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14
Q

How does [glucose] and [FA} impact GH?

A

A sharp drop in [glucose] or [FA}, such as in short-term fasting

–> increase plasma GH

Elevation of glucose or FFA, such as in obesity

–> reduces plasma GH

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15
Q

How do deep vs light sleep impact GH?

How do various stresses (trauma, surgery, fever) impact GH?

A

Deeper sleep –> more GH

Stress increases plasma GH

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16
Q

What do children who have GH deficiency look like?

What does GH replacement therapy cause?

A

Short & moderately obese

GH therapy

  • enhances positive nitrogen balance
  • decreases urea production
  • redistributes fats
  • reduces carbohydrate utilization
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17
Q

Unlike other hormones, GH for humans must come from

A

other primates

(e.g. cant use pig like insulin

18
Q

mechanism of GH at the receptor

A
  1. GH binds to JAK-STAT receptor dimer
    1. Intracellular domains dock and activate the JAK-STAT tyrosine kinase pathway
  2. Activated JAK tyrosine kinases phposphorylate STAT transcription factors –> activates GH-dependent gene transcription and expression
19
Q
A
20
Q

Somatomedins / IGFs

where do they originate? what are they produced in response to?

What happens if you have high GH but not IGF?

A

Produced in response to GH and are produced by many tissues, but mostly in the liver.

They mediate the typical GH responses, so not having IGFs –> retarded growth despite high GH

21
Q

How are IGF’s availability to tissues regulate?

A

They circulate bound to large binding proteins

22
Q

Both IGFs, but especially __, are greatly reduced in the plasma of GH-deficient subjects

A

IGF-1 is greatly reduecd in the plasma of GH-deficient subjects

23
Q

Describe IGF & GH levels in the fasting condition

A

High GH, low IGF

Because fasting -> low insulin, high GH -> IGFs activated neg feedbacks on itself to low IGF (but GH stays high in response to low IGF) ?

24
Q

Locally-produced IGF-1 contributes to the stimulatory effects of GH, especially ____

A

enhancement of longitudinal growth

25
Q

GH & IGF in longitudinal growth of bones

A

GH –> stimulate differentiation of prechondrocytes into early chondrocytes, which secrete IGF-1

IGF –> stimulate clonal expansion and chondrocyte maturation

26
Q

Administration of IGFs to GH-deficient children or adults decreases has what impact on:

  • plasma amino acid levels
  • lean body mass
  • fat mass
  • bone formation
  • resting metabolic rate, exercise capacity, well-being
A

amino acid lvls decrease bc *protein synthesis*

lean body mass INcrease & fat mass DEcreases

Bone formation is enhanced

Metabolic rate, exercise capacity, and wellbeing INcrease

27
Q

The most specific effect of GH is

A

Acceleration of linear cartilage growth center growth in long bones

Cartilage-forming cells stimulated during collagen & proteoglycan chondroitin synthesis, which forms the ECM of cartilage

28
Q

Most specific tissues share in the anabolic response to GH

A

GH stimulates DNA, RNA, and protein synthesis in almost all cell types.

29
Q

GH & senescence

A

Decrease in GH with aging –> less anabolic effects

30
Q

In what ways does GH oppose the actions of insulin?

A
  • GH stimulates insulin gene expression, BUT it also induces insulin resistance
  • Inhibits glucose uptake by muscle & adipose cells –> increase plasma glucose
  • Enhances lipolysis & opposes insulin’s lipogenesis
31
Q

GH is a ___genic hormone

A

diabetogenic

32
Q

GH has what impact on plasma free FA and ketoacids? What about on adipose tissue?

A

Increases plasma fFA & ketoacids

Decreases adipose tissue

33
Q

Acromegaly

A

Excessive GH secretion after puberty

  • Causes: pituitary tumor, hyperpituitarism, somatotroph tumors
  • Characteristics:
    • Thick & oily skin, esp face and scalp
    • Delayed diagnosis: often not diagnosed until 15-20yrs old
34
Q

Both GH & insulin together augment ____, leading to increased lean body mass.

What is the purpose of insulin-antagonistic effect of GH?

What happens to insulin, GH, and IGF during fasting?

A

Together, they augment IGF production

The insulin-anatagonistic effect of GH prevents hypoglycemia when you’re fasting (dont want high insulin)

Fasting: GH rises -> inuslin falls -> IGF declines

35
Q

Prolactin’s structure is homologous to ___ and is synthesized as a ___.

What happens to it in the ER? In the Golgi?

A

Homologous to GH

Synthesized as a preprohormone

Temporarily N-glycosylated in the ER

Deglycosylated in the Golgi

36
Q

What form of prolactin is the major circulating form in NONpregnant women?

A

Glycosylated prolactin is constituvely secreted because it exhibits lower biological activity

37
Q

Prolactin secretion is regulated by

A
  • Inhibited:
    • Dopamine
    • Somatostatin
    • <strong>GnRH (alternative form)</strong>
  • Stimulated: TRH
38
Q

Biological effects of prolactin

A
  • Breat development
  • Milk production
  • Reproductive function in both genders
39
Q

Disruption of pituitary connections to hypothalamus can have what impact on prolactin secretion?

A

Increase prolactin secretion

40
Q

Why does excess prolactin cause infertility in women and men?

A

Excess prolactin inhibits GnRH release –> lack of ovulation, decreased sperm production

41
Q

__ contributes to stimulation of parental protective behavior in newborns

A

prolactin

42
Q
A

Physiology (42 decks)

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