Lecture 8 Flashcards
Dopamine normally inhibits PRL.
G-alpha protein inhibits cAMP.
G-beta protein activates K+ in channels and inhibits Ca2+ channels.
Postpartum depression:
Dopamine goes down to facilitate lactation. Makes mother sad.
Thyroid gland cell types:
Follicular cells: secrete T3 and T4.
Parafollicular or C cells: release calcitonin, a calcium/phosphate regulator.
Average size of thyroid gland:
20-34 g
Unique characteristic of thyroid hormones:
They are peptides, but their receptors are in the nucleus rather than on the cell membrane. They have a similar mechanism of action as steroids.
Storage of thyroid hormones:
Follicular epithelial cells are filled with glycoprotein mixture called colloid. The colloid holds 3 months of thyroid hormone.
Synthesis of thyroid hormones:
Thyroglobulin synthesis: from RER of follicular cells.
Iodine trapping: Na/I symporter on basolateral membrane.
Oxidation of iodine: thyroid peroxidase in lumen oxidizes I- to I2.
Iodination of thyrosine: thyroid peroxidase in lumen makes mono- and di-iodothyrosine.
Coupling reaction: thyroid peroxidase catalyzes formation of T3 and T4 from mono/dis.
Endocytosis of thyroglobulin: TSH stimulates follicular cells to endocytose T3/T4.
Proteolysis: lysosomal proteases in the vesicle hydrolyse peptide bonds and release T3/T4.
Deiodination: thyroid deiodinase recycles iodine from unused mono/dis.
TSH’s role in thyroid hormone synthesis:
Enhances Na/I symporter activity.
Why does iodine need to be oxidized?
Negatively charged iodide can’t bind to thyroglobulin.
T3 vs T4:
10x more T4 than T3.
How do T3/T4 endocytic vesicles travel to the basolateral membrane?
Microtubular action of cytoplasm.
Physiological functions of thyroid hormone:
Growth and development Increase basal metabolic rate Increase O2 consumption Increase Na/K ATPase activity Stimulate thermogenesis Stimulate macromolecule metabolism
Thyroid hormone stimulates pretty much everything except:
Decreases serum cholesterol concentration.
Effect of thyroid hormone on: bone
Increases osteoblastic and osteoclastic activity for normal growth and development.
Effect of thyroid hormone on: liver
Stimulates triglyceride and cholesterol metabolism.
Effect of thyroid hormone on: brain
Stimulates axon growth and development.
Effect of thyroid hormone on: heart
Increase adrenergic receptors, increase response to catecholamines, reduce smooth muscle resistance.
Effect of thyroid hormone on: adipose tissue
Stimulates lipolysis.
Effect of thyroid hormone on: muscle
Stimulates protein breakdown.
Effect of thyroid hormone on: gut
Stimulates carb absorption.
T3: target? comparative activity? half-life?
Negative feedback on ant pit and hypothalamus.
More physiologically active than T4.
Half-life of 1 day.
Making T3 from T4:
5’/3’ deiodinase converts T3 into T4.
T4: half-life? comparative activity?
Half-life of 6-7 days.
Less active than T3.
rT3: activity? structure?
Physiologically inactive.
Two iodines on outer benzyl instead of inner.
Structures of T3, T4, and rT3:
T3 has two I on the inner ring and one I on the outer ring.
T4 has two I on both rings.
rT3 has two I on the outer ring and one I on the inner ring.
Making rT3 from T4:
5/3 deiodinase converts T4 to rT3.
Two forms of 5’/3’ deiodinase:
Type 1: liver, kidneys, thyroid. General circulation.
Type 2: pit, CNS, placenta. Local.
Thyroid hormones inside thyroglobulin:
Part of the backbone. Need two cleavages to be free.
How much T3 is free? How much T4 is free?
T3: 0.5%
T4: 0.02%
Transport of thyroid hormone:
Free or bound to thyroxine-binding globulin.
Pregnancy vs thyroxine-binding globulin:
Estrogen stimulates synthesis of TBG, which reduces level of free thyroid hormone, which stimulates synthesis of more.
Liver failure vs thyroxine-binding globulin:
Reduced TBH synthesis leads to increased levels of free thyroid hormone, which inhibits synthesis of more.
Hypothyroidism: what is it? treatment?
Primary: problems with thyroid gland. Secondary: problems with pit or hyp.
Treat primary with thyroid hormones.
Treat secondary by manipulating regulators.
Disorders related to hypothyroidism:
Cretinism
Myxedema: cutaneous/dermal edema caused by too much deposition of connective tissues
Iodine-deficient goiter
Hyperthyroidism: related disorders
Graves: autoimmune condition. B lymphocytes synthesize abnormal immunoglobulin that binds and activates TSH receptor. Iodine trapping increases. Goiter.
