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Endocrinology II

Lecture 2 of 3 on Endocrine System/Endocrinology
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Growth Hormone
Primary hormone involved in human growth; Secreted throughout life but declines with age; Produced by somatotroph cells in anterior pituitary gland; Stimulated by hypothalamic _ _RH release into the portal system; Inhibited by hypothalamic somatostatin and feedback mechanisms; Targets bone, liver, and fat tissues as main targets; This hormone has direct and indirect effects (indirect effects mediated by liver insulin-like growth factors--IGFs); Proliferation/survival effects = stimulates linear growth, increases organ growth, increases muscle mass; Stimulates lipolysis (decreases fat depots); This hormone responses mediated by 3 receptor signaling pathways (G protein coupled receptors, cytokine receptors, tyrosine receptor kinases)
Somatostatin
Negative regulator; Binds to G protein receptor; Found on all anterior pituitary cells; Pathway hypothalamus causes to damptem systems
Adipose Tissue
Direct effects of growth hormone on this; Stimulates lipolysis, increasing blood free fatty acid content; Decreases glucose uptake
Liver
Direct effects of growth hormone on this; Increases gluconeogenesis; Increases IGF production
Muscle
Direct effects of growth hormone on this; Stimulates amino acid uptake/protein syntehsis, increasing lean body mass; Decreases glucose uptake (net effect of glucose on all 3 tissues is increases blood glucose levels--diabetogenic)
Indirect effects of Growth Hormone
(From IGF signaling) Increase organ size and function (increased cell survival/proliferation/ differentiation); Stimulate bone condrocyte function at epiphyseal plates to enhance linear growth; Increase in lean muscle mass may be predominantly an IGF effect`
Thyroid Stimulating Hormone (TSH)
Regulated by hypothalamic TRH (thryoid hormone releasing hormone); TRH binds thyrotroph G protein coupled receptors for ___ (hormone) release); This hormone binds to thyroid follicular cells G protein coupled receptors for T3/T4 synthesis/release; T3/T4 are lypophilic and enters/binds to cytoplasmic steroid class of receptors in target cells
Thyroid Hormones
Regulates basal metabolic rate (BMR); Key in bone and nervous sytem development; Increases gut carbohydrate absorption; Decreases circulating cholesterol; Stimulates lipolysis; Increased protein breakdown (resulting in weight loss if food is not increased); Facilitates autonomic fucntion (ionotropic and chronotropic)
Thyroid Hormone (T3/T4) Biosynthesis
Dietary iodide is key substrate for synthesis on thyroglobulin (TG); Synthesis occurs in colloid; Products formed in cells; T3 is 4x more active; T4 is 20x more abundant; T4 is converted to T3 by deiodinases in tissues
Hyperthyroidism
Too much thyroid hormone; People are "hyper"; BMR 10-1000% above normal; Nervousness, fine tremor at the fingers; Weight loss, hyperphagia; Increase pule pressure, heat intolerant, sweating; Grave's disease
Grave's Disease
Related to hyperthyroidism; TSH antibodies activate thyroid receptors resulting in increased T3/T4 production (low circulating TSH)
Hypothyroidism
Too little thyroid hormone; BMR falls to 40% of normal; "Can't think", poor memory; Lethargic, listless; Skin dry, poor cold tolerance; Children with this develop poorly (dwarfed) and can show mental retardation (cretinism); Treatment = hormone supplements; Hashimoto's disease
Hashimoto's Disease
Related to hypothyroidism; Autoimmune antibodies destroy thyroid gland
Cretinism
Can develop in hypothyroid children; Children can show mental retardation
Parathyroid Hormone (PTH)
Involved in calcium homeostatsis; Produced by parathyroid gland; Activates G protein coupled receptors on target tissues (bone, kidney)
Calcium Homeostasis
Calcium importance = bone maintenance, nervous system signaling, muscle contraction/skeletal/smooth/cardiac, blood clotting, others; Three regulators = parathyroid hormone (PTH), vitamin D, calcitonin; Three integrated sites of action = bone (largest reservoir of body calcium), GI calcium absorption, kidney calcium excretion; Free (ionized) calcium is active (50% free-50% bound); PTH and blood calcium levels are tightly balanced; Drop in blood calcium leads to increased PTH release; PTH increases kidney calcium reabsorption (fast); PTH increases bone resorption to free calcium (slow); PTH stimulates kidney vitamin D synthesis (1,25-[OH]2D); 1,25-(OH)2D binds to GI steroid-type receptors to stimulate calcium absorption
Vitamin D
Involved in calcium homeostasis; Not one but class of compounds; Synthesis in 3 tissues (skin, liver, kidney); Parathyroid hormone (PTH) important in final synthesis of active vitamin D in kidney
Calcitonin
Peptide produced by thyroid C cells; Decreases blood calcium (opposite effects of PTH and vitamin D); Blood calcium so tightly coupled with PTH/vitamin D that calcitonin is more important development than in adults