5. Bone Growth and Mass

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Created by jxv135 over 7 years ago


Endo/Sex Lecture 5

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Question Answer
Hormones involved with body mass -Insulin -Glucocorticoids -Adiponectin -Leptin
Hormones involved with Linear growth -GH -IGF1, IGF2 -Insulin -Thyroid hormone -Glucocorticoids -Androgens -Estrogens
Where is GH secreted from? Somatotrophs in the anterior pituitary
What are the forms of GH? - 22.5 KDa -20 KDa -45 KDa (22.5 x2)
Hormones homologous to GH? -pvGH -hCS1 and hCS2 -Prolactin
Where is GHRH released from? small neurons of the arcate nucleus in the hypothalamus
General GH Pathway Hypothalamus releases GHRH which lands on G-alpha-s receptor on somatotrophs of the Anterior Pituitary (increase cAMP and Ca+) --> release GH
When is GH secretion increased? exercise, stress, fasting, high protein meal, fasting
When is GH secretion downregulated? It inhibits itself. GHRH release also means Somatostatin release which inhibits GH
Maturation of GH protein RER = Pre-Pro-Hormone Golgi = ProHormone -Secreted as Hormone
GH Secretion pattern? Spikes when you sleep (12am-4am)
GH signals by which pathway? RTK --> Jak/Stat
Effects of GH on target tissue Increase lipolysis, decreased glucose uptake, increased hepatic gluconeogenesis, Insulin resistance (high doses of GH)
Effect of GH on the bones -stimulates chondrocyte growth -promotes longitudinal bone growth -stimulates extracellular matrix formation
Ghrelin and GH -Ghrelin involved in post meal stimulation of GH -Stimulates appetite -Interacts with GH secretogue receptor (GHRH) --- distinct from GHRH receptor
Somatostatin Released from the Periventricular Nucleus of the hypothalamus. -Inhibits GH release by activated G-alpha-i pathway on somatotrophs
IGF interplay with GH Made in the liver. Upregulates the Somatostatin release from the PVN in the hypothalamus which blocks GH release from anterior pituitary (Direct Effect).
Indirect effects of IGF-1 supresses GHRH release from the Arcate Nucleus of the hypothalamus
IGF-1 is similar to what hormone in terms of receptor structure/activation? Insulin RTK
IGF release in Aging Huge spike prior to puberty and then goes down
IGF-2 -Less dependent on GH -Promotes cell growth through IGF-1 receptor
When is IGF-2 more predominant? During Fetal Growth
Describe Insulin, IGF-1, and IGF-2 receptors Insulin and IGF-1 receptors are almost identical, except IGF-1 has longer cytosolic domain. Both are RTKs with receptors that are heterodimes (disulfide bonds) IGF-2 receptor is a singular mannose-6-phosphate receptor
Insulin Signaling Path (S)tan (G)ot (R)atchet(s) (R)eady (F)or (Me) (Ma)n
IGF-1 Signaling pathway homodimer signal binds to homodimer receptor -->activates IRS IRS activates RAS/RAF/MAP as well as P13K-->AKT which upregulates genes for recruiting microtubules to translocate GLUT4 to the muscle for insulin mediated uptake
IGF-2 signaling activates ILK and P13K -->AKT to produce cytoskeletal reorganization (elongation of MTs)
De-regulation or imbalance of IGF binding proteins leads to what? -Atherosclerosis -Cancer -Chronic kidney disease -Diabetic Neuropathy -Osteoperosis -Rheumatic disease -Type 2 Diabetes
Macrosomy Mother's insulin reaches the baby's body and causes major growth. The mother will show with gestational diabetes
Leprochaunism IR defect IR can bind insulin but doesn't initiate the signaling cascade
Factors that decrease growth Glucocorticoids --> moves Ca+ out -Lack of T3 -IR defect
Factors increasing GH Deep Sleep, exercise, Niacin, Fasting, Increased testosterone, GHRH, L-DOPA, Inhibitors of somatostatin (hypoglycemia, arginine, propanolol)
Decreases in HGH DHT, Medications, high blood sugar, somatostatin (IGF-1)
Dwarfism absence of GH before puberty
Gigantism Excess of GH before puberty
Acromegaly Excess of GH post puberty
How does replacement therapy with GH affect the body? Increase in lean mass and decrease in body fat
Signs of GH deficiency? Decreasing muscle strength, Osteoperosis, Increasing body fat, decreasing collagen production, wrinkles, cellulite, arthritis, decreased energy, moodiness, anxiety, depression
Clinical manifestations of GH Deficiency central adioposity, Insulin resistance, ARTHEROSCLEROSIS
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