Growth Hormone

Question 1

What stimulates GH synthesis and secretion?

Answer 1

GHRH

Question 2

What inhibits GH synthesis and secretion?

Answer 2

SS

Question 3

What increases GH secretion from the pituitary?

Answer 3

grehlin, neuroendocrine peptide from gastric mucosa

Question 4

Majority of GH secretion occours what time of day and characteristic of secretion?

Answer 4

up to 70% in first episode slow wave wave of deep sleep, peaks again during slow wave cycles later on in the night,

Question 5

What happens to GH secretion with age? why?

Answer 5

decline; due to decline in slow wave deep sleep from early adulthood to middle age is the likely culprit

Question 6

What is the mechanism utilized by the somatropes in the pituitary that accounts for changes in GH secretion?

Answer 6

GHRH utilizes a Gs receptor and SS a Gi receptor, both act on andenylate cyclase to stimulate or inhibit the cAMP pathway leading to exocytosis f GH in vesicles triggered by intracellular Ca

Question 7

How does GH circulate? Why?

Answer 7

bound to a low affinity and a high affinity protein; increases 1/2 life by decreasing renal clearance and damp oscillations in serum levels associated with pulsatile release

Question 8

GH acts on adipose tissue affecting what processes and to what result overall?

Answer 8

decreased glucose uptake and increase lipolysis; decreased adiposity

Question 9

What affect does GH have on the liver?

Answer 9

increase in: RNA synth, protein synth, gluconeogenesis, IGFBP and IGFs

Question 10

What affect does GH have on the kidney, pancreas, intestine, islet cells, parathyroids and skin, and to what over all result? What else achieves this?

Answer 10

increase in: RNA synthesis, protein synth, DNA synth, cell size and number; increase organ size and function; IGF

Question 11

GH acts on muscle tissue affecting what processes and to what result overall? What else achieves this?

Answer 11

decrease glucose uptake, increased AA uptake, increased protein synthesis; increased lean mass; IGF

Question 12

GH acts on chondrocytes affecting what processes and to what result overall? What else achieves this?

Answer 12

increase in: RNA synthesis, protein synth, DNA synth, cell size and number, chondroitin sulfate, collagen; increased linear growth; IGF

Question 13

What tissues produce IGF and how does it circulate?

Answer 13

liver (70%) and GH target tissues (30%), bound to IGFBP

Question 14

How does GH mediate its signal inside the cell?

Answer 14

inducing receptor homodimerization, JAKs phosphorylate each other upon GH to receptor, receptor then autophosphorylates or transphosphorylate, JAKs phosphorylate STATs (signal transducers and activators of transcription)causing them to dimerized and enter the nucleus

Question 15

What is the difference in IGF I and IGF II? How do they affect growth?

Answer 15

I is major form in adults, II is the major form in the fetus; IGFs affect proliferation and differentiation of cells

Question 16

What three categories do defects (diseases) in GH fall into?

Answer 16

GH or GHRH synthesis or production, receptor defects, GH binding proteins

Question 17

What happens if there is a deficiency in GH?

Answer 17

hepatocytes fail to release IGF, target organs are not affected, growth is inhibited

Question 18

What happens in GH insensitivity syndrome?

Answer 18

GH receptors are mutated, although enough GH is produced hepatocytes are unresponsive, serum IGF reduced causing a decrease growth of responsive tissues; inhibitory effects of IGF on GH are reduced and serum GH concentrations are increased

Question 19

What are causes of hyposecretion of GH? clinical affects?

Answer 19

GH receptor mutations, deletion or mutation of GH gene, biologically inactive GH, or no IGF1 production in response to GH; growth retardations and short stature (Laron dwarfism and African pygmies

Question 20

What are the disorders of hypersecretion of GH how are they distinguished from each other?

Answer 20

acromegaly (adult onset) and gigantism (childhood onset)

Question 21

what are the clinical features and likely cause of acromegaly?

Answer 21

abnormal facial features due to increased periosteal bone growth, usually GH secreting pituitary tumors, rarely extra-pituitary disorder, excessive GHRH from hypothalamic tumors

Question 22

What are the common causes of GH insensitivity?

Answer 22

GH receptor defect (Laron dwarfism), post receptor defect in IGF generation (African pygmies, resistance to IGF (LD and some AP characterized by low level of GHBP and IGFBP)

Question 23

What are the effects and side effects of GH treatment in GH deficiency?

Answer 23

effects: decreased adipose, subcutaneous and intra-abdominal, increased lean body mass, increased exercise capacity and muscle strength; side effects: edema and arthralgia or myalgia (dose dependent)

Question 24

How is GH being used in elderly?

Answer 24

delay physical decline associated with aging

Question 25

how is treatment for hypersecretion of GH treated?

Answer 25

Octreotide, SS analog, bonds predominantly to SSTR2 and SSTR5 receptors in somatrophs inhibiting GH secretion, (Lanreotide another analogue but not legal in US) or Pegvisomat a GH analogue with AA substitutions preventing receptor dimerization (higher affinity for receptor than GH)