BIOL 2P93 Lecture Notes - Nuclear Receptor, Goitre, Pinocytosis

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Thyroid Physiology
I. Introduction
a. Anatomy
i. Generally bilobed, but some people have small 3rd lobe (pyramidal lobe)
II. The thyroid gland synthesizes, stores, & secretes the thyroid hormones—
principally thyroxine (T4) & to a lesser extent triiodothyronine (T3)
a. Biochemistry & hormonogenesis
i. iodine trapped by Na-I Cotransporter in cell membrane
ii. iodine transported to apical membrane (via transporter)
iii. thyroglobulin produced & stored in follicle
iv. thyroid peroxidase (TPO) ionizes iodine & links it to thyroglobulin
covalently = Organification
v. this => monoiodotyrosine; diodotyrosine, etc
vi. Coupling = 2 tyrosines (w/ iodine) are linked together => thyroxine (T4)
vii. pinocytosis & transport of thyroid hormones across cell
viii. secretion at basal membrane
III. Dietary iodine is a substrate for thyroid hormone synthesis, but in larger
amounts it can inhibit thyroid hormone production (autoregulation)
a. iodine is trapped, oxidized, & covalently bound to tyrosines in thyroglobulin =>
vital in thyroid hormone production
b. Iodine deficiencies
i. ↑ fractional iodine uptake by the thyroid
ii. ↑ thyroid gland size (goiter)
iii. hypothyroidism
iv. Cretinism—iodine deficiency during gestation => irreversible brain
damage
c. Autoregulation
i. lg amounts of iodine => inhibition of thyroid hormone production/release
ii. thyroid gland can “escape” from the inhibitory effects of ↑ iodine after 2
weeks
iii. combination of these factors allow for uncoupling of T3/T4 production
from the amount of iodine ingested daily
IV. Thyroid gland function is controlled by hypothalamic TRH and pituitary TSH
which are in turn regulated by the negative feedback of thyroid hormones
a. TSH (secreted from thyrotropes of ant. pituitary) binds TSH-R (GPCR)
activates adenylyl cyclase ↑ [cAMP] ↑T4/T3 production
b. H-P-thyroid axis responds to hyperthyroidism & hypothyroidism (over/under
production of T3/T4)
(Raymond has removed a diagram showing TRH, TSH, and T3/T4 regulation by the
hypothalamus, pituitary, and thyroid.)
V. In plasma, most T4 & T3 circulate bound to carrier proteins, with only a small
unbound (free) fraction available for target tissue exchange and action
a. only 0.03% T4 & 0.3% T3 are unbound (free)
1
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