Lecture 8 Flashcards by Daisy Ko

Dopamine normally inhibits PRL.

G-alpha protein inhibits cAMP.

G-beta protein activates K+ in channels and inhibits Ca2+ channels.

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Postpartum depression:

Dopamine goes down to facilitate lactation. Makes mother sad.

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Thyroid gland cell types:

Follicular cells: secrete T3 and T4.

Parafollicular or C cells: release calcitonin, a calcium/phosphate regulator.

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Average size of thyroid gland:

20-34 g

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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.

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Storage of thyroid hormones:

Follicular epithelial cells are filled with glycoprotein mixture called colloid. The colloid holds 3 months of thyroid hormone.

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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.

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TSH’s role in thyroid hormone synthesis:

Enhances Na/I symporter activity.

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Why does iodine need to be oxidized?

Negatively charged iodide can’t bind to thyroglobulin.

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T3 vs T4:

10x more T4 than T3.

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How do T3/T4 endocytic vesicles travel to the basolateral membrane?

Microtubular action of cytoplasm.

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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

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Thyroid hormone stimulates pretty much everything except:

Decreases serum cholesterol concentration.

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Effect of thyroid hormone on: bone

Increases osteoblastic and osteoclastic activity for normal growth and development.

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Effect of thyroid hormone on: liver

Stimulates triglyceride and cholesterol metabolism.

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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.