Growth Hormone Flashcards
Where is growth hormone releasing hormone (GHRH) released from?
- Hypothalamus (PVN)
- GHRH or somatocrinin
Where is growth hormone released from?
- Anterior pituitary
- Somatotrophs
- Two forms: one derived from all five exons, one missing part of exon III
What is the target tissue for growth hormone?
- Liver (IGF-1)
- Muscle and bones
- Adipose tissue
How is GH secretion regulated?
- Hypothalamic hormones: GHRH stimulates and somatostatin inhibits
- GHRH binds to its receptor GHRHR (GPCR) on somatotrophs -> increased cAMP -> increased synthesis
- cAMP also stimulates opening of calcium and potassium channels -> secretion
- GHRHR also expressed in pancreas and GI tract
- GH secretion follows a pulsatile pattern (peaks at night) and aligns with circadian rhythms
- Increased by sleep, stress, hormone related to puberty, starvation, exercise, hypoglycemia
- Increases from birth to childhood
- Peaks during puberty
- Decreased by somatostatin, obesity, hyperglycemia, pregnancy
How is GH synthesized?
- Peptide hormone
- GH gene (GH1) on chromosome 17
- Transcription and translation of GH1 -> prepro-hormone
- Prepro-GH has an N-terminal signal peptide that directs it to rough ER
- Signal peptide is cleaved off as the protein enters the ER -> pro-growth hormone
- In ER and golgi, post-translational modifications -> remove any remaining inactive segments
- Mature hormone stored in vesicles
How is GH transported in blood?
By GH-binding proteins (GHBPs)
How does Ghrelin impact GH secretion?
- Ghrelin released during fasting
- Enhances GH secretion (acts as a secretagogue)
How does IGF-1 impact GH secretion?
- IGF-1 produced in response to GH
- Feeds back to hypothalamus and pituitary to modulate GH levels
- Elevated IGF-1 levels -> increase somatostatin release -> further inhibit GH
Explain the action of GH.
- Crucial for body growth, cell repair, and metabolic regulation
- Causes growth of almost all tissues of the body (that are capable of growing)
- Increases cell size, mitosis, and cell numbers (and cell differentiation)
- Impacts body composition, increasing lean muscle mass and bone mass (increases rate of protein synthesis)
- Necessary for maintaining glucose and lipid homeostasis
- Increases mobilization of fatty acids from adipose tissue, circulating free fatty acids in blood, and usage of fatty acids for energy
- Decreases rate of glucose utilization throughout body
- Enhances body protein, uses up fat stores, and conserves carbs
Explain the differences and similarities between GH and insulin.
- Insulin and GH similar stages of protein synthesis (minus C-peptide)
- Insulin: gets glucose into tissue and increases fat
- GH: gets glucose out and decreases fat
- Both can utilize P13K-Akt pathway
- Tyrosine kinase receptors
GH receptors
- GHR present mainly in liver (IGF-1), muscle, and adipose tissue (also present in bone, brain)
- Tyrosine kinase
- Activation of JAK2 (remember leptin) initiates downstream signaling pathways
Explain the JAK-STAT pathway.
JAK2 phosphorylation (due to binding) -> STAT activation -> promoting transcription of target genes
Explain the MAPK pathway.
Activates RAS/REF/MEK/ERK cascade -> important for cell growth and division
Explain the P13K-Akt pathway.
- Involved in protein synthesis, anti-apoptotic responses, and metabolism regulation
Somatomedins
- GH causes liver to synthesize and release small proteins called somatomedins (insulin-like growth factors)
- Somatomedin C (IGF-1) produced in liver
- GH can also stimulate local IGF-1 production in tissues, where it acts in a paracrine or autocrine manner to mediate local growth effect