PHGY 210 endocrinology
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- increase Na absorption in the kidney, control blood pressure.
- increase K and H loss via urination, maintain electrochemical balance.
- increase plasma Ca concentration. increase bone absorption, kidney absorption and Vit D synthesis. work with vit D to increase absorption of Ca in the gut.
- 84 AA long, 34 AA at N-terminus essential for active parathyroid receptor.
- hypo: tetany, muscle spasm (affect larynseal muscle, get asphaxiation). decrease vit D syn. Eat Vit D and Ca supplement.
- Hyper: adenoma, form kidney stone. cardiac arrhythmias, decrease neural excitability, Ca deposits on blood vessel walls and bone cartilage. remove tumor and replacement therapy.
- 1. salt retention, aldosterone back up.
- 2. protein and carb metabolism. increase gluconeogenic enzyme in liver, increase AA break down in muscle and adipose tissue. increase plasma glucose concentration.
- 3. lipid metabolism, increase lipolytic enzymes in adipose cells. excess lead to hyperlipidemia and hypercholesterolemia. increase lipolytic action of other hormones.
- 4. anti-inflammatory and immunosuppression, atropy of lympatic system, reduce antibody formation, decrease circulating lymphocytes. decrease histamine formation and allergy.
- 5. bone, decrease protein matrix. osteroporosis.
- decrease plasma Ca concentration.
- not essential for Ca homeostasis.
- 32 AA all essential protein.
- receptor in thyroid gland.
- produced in C cells of thyroid glands.
- increase bone deposition and decrease excretion by urine.
- synthesis: 1. UVB + 7-dehydrocholesterol in skin. 2. 25-hydroxylation in liver. 3. 1-hydosylation in kidney (defective if renal disease).
- synthesized from cholesterol, eat from cod liver oil and fatty fish.
- function: increase plasma Ca concentration, part of immune system (antiinflammatory), anticancer.
- low level: rickets (children), osteomalacia (adult).
Difference between autocrine, paracrine and endocrine signaling.
- autocrine: short distance, act on adjacent cell.
- paracrine: short distance, act on cell itself.
- endocrine: long distance, act on different cell.
Communication by hormones via six steps.
- 1. synthesis (control amount of hormone).
- 2. release (control timing of hormone action).
- 3. transport (localize hormone, protein carrier).
- 4. detection (specificity).
- 5. change in metabolism (cascade, amplification).
- 6. removal (half life, period/timing of hormone action).
Classical endocrine organs.
- 1. brain: hypothalamus, anterior pituitary.
- 2. heart: atrial natriuretic peptides.
- 3. thyroid, parathyroid glands.
- 4. adrenal gland: cortex and medulla.
- 5. ovary.
- 6. testis.
- 7. pancreas: islets of Langerhans.
Classes of hormones.
- 1. protein: christmas tree with decors.
- 2. polypeptides: christmas tree.
- 3. steroids: synthesized from cholesterol.
- 4. amines: derived from tyrosine.
- 5. ionic calcium: multiple function, ex. neurotransmitter.
hypothalamic pituitary signaling.
- from hypothalamus to anterior pituitary (hypothalamic hypophyseal portal system) via the blood vessels in the pituitary stalk.
- 6 types of hormones in the anterior pituitary can be activated or inhibited.
- burn out methyl groups.
- convert aldosterone to estradiol.
- once methyl group comes off, spontaneous reaction involving carboxylation.
not a thyroid hormone.
hormone receptor property and regulation.
- Properties: specificity, affinity, saturability and measurable biological effect.
- regulation: increase number of receptors or increase their sensitivity (amplitude of signaling).
name two posterior pituitary hormones.
- 1. vasopressin
- 2. oxytocin
name six anterior pituitary hormones. which one is not a peptide.
- 1. thyrotropin-releasing hormone TRH
- 2. gonadotropin-releasing hormone GnRH
- 3. somatostatin
- 4. growth hormone-releasing hormone GRH
- 5. prolactin-inhibiting hormone PIH dopamine *
- 6. corticotropin-releasing hormone CRH
posterior pituitary gland
- vasopressin and oxytocin are synthesized in two hypothalamic nuclei - supraoptic nucleus and paraventricular nucleus.
- prohormones are processed in secretory granules during axonal transport.
- mature hormones are liverated from neurophysins.
- hormones are transported down the pituitary stalk.
Contrast the effect of oxytocin in female and male.
- female: parturition, uterus sensitive, cause dilation of uterus cervix and expulsion of fetus and placenta. milk ejection, stimulus is suckling.
- male: ejaculation, assist epididymal passage of sperm.
- similarities: behavioral effects, reduce anxiety, increase pro-social behaviours.
- 15-20g, 3g essential to be healthy.
- has colloid, composed largely of thyroglobulin, surrounded by follicles.
- T3 and T4 are split off from thyroglobulin.
- synthesis of amines are under TSH control (pituitary).
- thyroglobulin is a storage for T3 and T4.
convert T4 to T3.
thyroid hormone synthesis.
- I2 + tyrosine in thyroglobulin -> MIT and DIT
- MIT + DIT --> T3
- DIT + DIT --> T4
- process: oxidative coupling
- TSH increases T3 and T4 rate limiting step.
T3 and T4 regulation
- TRH --> TSH --> T3 and T4 and negative feedback.
- TSH act on receptors on the follicular cells.
- non-toxic goiter.
- no T3 and T4 produced, TRH and TSH production goes up but still no T3 and T4 are produced.
effect of thyroid hormones. 4 in adults, 1 in children.
- A. calorigenesis stimulation, increase cardiac output, oxygenation of blood, rate of breathing and RBCs.
- B. carb metabolism, glycogen formation in liver, increase glucose uptake.
- C. lipid turnover, increase lipid synthesis and oxidation.
- D. protein metabolism, increase protein synthesis.
- 1. normal growth, physical and neural development.
- absence: irreversible mental retardation. stimulate syn of nerve growth factor NGF, induces dendritogenesis and regenaration of sympathetic neurons.
T3 and T4 mechanism of action.
- 1. diffuse into nucleus, find cognate receptor, alter transcription.
- 2. interat with plasma memb and mito. not blocked by inhibitors of protein synthesis.
- 3. act directly at plasma memb, increase AA uptake. indep of protein syn.
- 1': myxedema. 4 causes: atrophy of the thyroid, autoimmune thyroiditis, goitrous hypothyroidism.
- 2': little TSH
- 3': little TRH.
- infantile: no thyroid gland or no thyroid hormone syn at birth. bad physical growth and mental development. dwarfism and mental retardation associated with cretinism.
- treatment: administer thyroid hormones.
- 1': toxic goiter, Grave's disease. 2 causes: Autoimmune, presence of Long Acting Thyroid Stimulator (LATS), mimic TSH. or thyroid adenoma/cancer, make T3 and T4 in absence of TSH stimulation.
- 2': pituitary tumor, no -ve feedback.
- 3': hypothalamic tumor, no -ve feedback.
- treatment: surgery, eat radioactive iodide (5mCi), antithyroid drugs (propylthiouracil). replacement therapy, watch the dosage.
5 roles of Ca.
- normal blood clotting
- maintain transmemb potential of cells
- excitability of nervous tissue
- contraction of muscles
- relase of hormones and neurotransmitter.
conc of Ca and location
- 10mg/1dL. 99% in bone, 50% bound, 50% free.
- obtained from diet, especially diary.
- adrenocorticotropin, 39 AA, syn as part of larger protein known as proopiomelanocortin (POMC).
- disease: congenital adrenal hyperplasia, lack of cortisol because of lack of enzyme 11b-hydroxylase.
- treatment: correct deficiency and normalize ACTH secretion.
- bind to ACTH recept on memb of middle and lower layer.
- cAMP cascade, activate steroidogenic enzyme, increase syn of steroid hormones.
- diurnal rhythm.
- indep of sleep and abolished by stress and Cushing's disease.
Effect of stress of glucocorticoids.
- increase the syn and release of CRH, ACTH and cortisol.
- advantage: provide energy
- disadvantage: cortisol inhibits wound healing
- increase blood glucose (diabetes mellitus), decrease immune response, loss of bone.
- cortex: lipid epithelial, from mesoderm. produce steroid hormones. glucocorticoids, mineralocorticoids, and progestins.
- medulla: chromaffin cells, from neural crest. add potassium bichromate, become fine brown granules. catecholamine epinerphrine and norepinephrine and peptide hormones (enkephalins, dynorphins and atrial natriuretic peptides).
adrenal cortex, 3 layers.
- upper: mineralocorticoids.
- middle: glucocorticoids.
- lower: glucocorticoids, progestins, androgen and estrogens.
- hypo: addison's. no adrenocortical hormones. atrophy of adrenal glands due to tubreculosis. treat with aldosterone.
- hyper: cushing's. too much ACTH. too much glucocorticoids and mineralocorticoids. surgery. lead to osteoporosis.
sevretes digestive enzymes.
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