thyroid physio vallano Flashcards
thyroid hormone regulates basal metabolic rate
-thyroid also secretes calcitonin but thats not related to metabolic rate.
-BMR is less than RMR
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thyroid gland layout
- thyroid of for growth, development, and metabolism.
- T3 is biologically active. reverseT3 is made at same rate at T3 but not active. T4 is produced most but is a prohormone, so gets made into T3 before becoming active. T3 and T4 are active forms of TH.
- thyroid is highly vascularized. and stores TH. has follicles (thyrocytes) that store TH in its lumen. Each follicle has a layer of epithelia that synthesize and secrete TH in response to TSH from anterior pituitary. stored TH is associated with thyroglobulin (TG) in the colloid gelatinous area of follicle.
TH are made from aa tyrosine on TG (thyroglobulin)
- TG has over 100 tyrosine residues, and some of them get cleaved to make T4.
- TH need iodide, provided from our diet.
- T3 is triiodothyronine and T4 is thyroxine
- synthesized from tyrosine resides off TG. TG is gelatinous.
- T4 get preferentially made.
- TH are only hormones that need an essential trace element (iodine)
iodide
- iodide stored in thyroid gland is associated with TG.
- need to ingest iodide to be in thyroid balance
- in thyroid gland, 2Na/I symporter concentrates iodide in thyroid gland. uses an inwardly directed electrochemical Na gradient. Not a pump, doesnt use ATP.
- gland can autoregulate. if dietary iodide is low, it can concentrate it
- chronic iodide deficiency leads to hypothyroidism that can be corrected by providing dietary iodide.
- most iodide in body is in thyroid gland associated with TG. rest is in target tissues as organic and inorganic iodide.
- TH gets metabolized and iodide gets secreted in urine and feces
TSH from anterior pituitary regulates synthesis, storage, and release of TH
- thyroid gland is follicular epithelial cells that synthesize and store T4 and T3 and release them into circulation. Synthesis is controlled by TSH, which is under negative feedback by thyroid hormones.
- synthesis and storage of TH:
- in the ER TG molecules are produced and put in vesicles and exocytodes into lumen of the follicle.
- Na/I symporter makes I from diet enter cell on basolateral side. Iodide then exits apical side using I/Cl antiporter
- in lumen of follicle, I is oxidized and attached to TG
- organification: binding of iodide to TG
- mature TG now. can be endocytosed back into follicle and stored as a colloid until secreted
- colloid proteolysis is stimulated by TSH. T3 and T4 exit the basolateral membrane and go into the blood.
Thyroid mainly secretes T4 but T3 is active. T4 gets converted to the more biologically active T3
- T4 is a prohormone.
- circulating TH is attached to TBG (thyroid binding globulin)
- other throid binding proteins: albumin and thransthyretin
- some TH is just free in blood
- T4 gets converted to T3 and rT3 by peripheral deiodinases in tissues like liver and kidneys.
- TH are also deaminated, conjugated, and decarboxylated
- pharmacological agents that inhibit conversion of T4 to T3 are things like propylthiouracil. this decreases over active thyroid. result is less thyroid hormone.
T4 vs T3
- T4 is a prohormone. T3 is biologically active.
- T4 half life is 7 days. T3 half life is 1 day.
- T4 biologic potency is 1, T3 is 4.
- T4 can be given to treat hypothyroidism. has a longer half life and more stable and leads to T3.
TH entry and transcriptional effects
T3 and T4 are in blood bound to TBG. Enter cell w.o TBG. T4 can enter nucleus, but usually it uses a monodeiodinase to convert it to T3.
- T3 then binds Thyroid hormone receptor (TR) in cell nucleus DNA. TH on TR heterodimerizes with RXR (retinoid X receptor) to regulate genes containing thyroid response element (TRE). Causes transcription:
- Na/K pump, Gluconeogenic enzymes, respiratory enzymes, myosin heavy chain, beta adrenergic receptors, and other things.
- overall affect is increase metabolic rate and O2 consumption.
TH have slow onset but long duration time
T3 acts 4X as fast at T4. latent 6-12 hrs and max effect in 2-3 days. T4 has max affect in 10 days.
TH transcriptional affects all tissues that regulate normal growth and development
- affects bone and CNS.
- in whole body, causes increase CO2 and ventilation. increase CO. increase urea and renal function.
- TH acts with GH to promote bone formation. promotes ossification and fusion of bone plates.
- in hypothyroidism, bone age is less than chronological age
- in hypothyroidism, excess replacement therapy with thyroxine leads to bone loss and osteoporosis.
- TH multiple effects on CNS and essential for CNS developmnt on perinatal period.
- TH deficiency in infants causes mental retardation (cretinism) and growth retardation. growth retardation can be fixed with treatment with T4 but cretinsim can only be treated with T4 soon after birth.
TH effects
T4 turns to T3 in target tissues.
-actions of T3 on target tissue:
growth: growth formation and bone formation
CNS: maturation
BMR: increase Na/K ATPase, O2 consumption, heat production, and BMR
metabolism: increase glucose absorption, glycogenolysis, gluconeogenesis, lipolysis, protein synthesis and degredation
cardiovascular: increase cardiac output
-for BMR, complete lack of TH secretion causes BMR to fall 50% below normal. excess secretion causes rate to be 60-100% above normal.
regulation
- HYPOthyroidism: increased serum cholesterol increases risk of atherosclerosis. LDL receptor expression and cholesterol excretion in bile are decreased in hypothyroidism.
- hypothyroid women on T4 must be monitored near menopause to prevent osteoporosis.
- in HYPERthyroidism, muscle wasting happens bc of proteolysis outweighing synthesis.
- in HYPERthyroidism, increased expression of Beta adrenergic receptors enhances sensitivity to epi and norepi. So, beta adrenergic antagonist help in decreasing symptoms of hyperthyroidism. Propanolol.
hypothalamus to pituitary to thyroid gland
- hypothalamus releases TRH onto anterior pituitary. Anterior pituitary secretes TSH onto thyroid. thyroid releases T3 and T4. T3 and T4 can feedback on either the TRH or TSH.
- TRH stimulates TSH release using a Gprotein coupled receptor linked to PLC, generating IP3 and intracellular Ca molbilization.
- TSH stimulates TH release through GPCR and adenylate cyclase with cAMP.
- dopamine and somatostatin exert inhibitory effects on TSH release.
TSH immunoassays
used to determine hypo or hyperthyroidism.
-high TSH indicates HYPOTHYROIDISM bc there isnt enough T3 or T4 to feedback on anterior pituitary. Low TSH indicates HYPERTHYROIDISM bc too much T3 and T4 inhibitng TSH release.
