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BIOL432: Molecular Endocrinology > Thyroid Hormones > Flashcards

Thyroid Hormones Flashcards

1
Q

What are the functions of thyroid hormones?

A

They increase oxygen consumption, basal metabolic rate, and thermogenesis/energy expenditure

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2
Q

What is the effect of thyroid hormone on glucose metabolism?

A

It increases glucose absorption in gut, promotes glycogen synthesis and glucose output by liver, affect insulin and glucagon levels, and insulin resistance in target tissues

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3
Q

What is the effect of T hormone on growth/development?

A

Promote fetal and childhood growth and CNS development

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4
Q

What is hyperthyroidism?

A

Overactive cells in the thyroid gland leading to excess THs. Leads to weight loss

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5
Q

What is hypothyroidism?

A

Underactive thyroid, weight gain. Caused by Hashimoto’s

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6
Q

What is the structure of thyroid hormone?

A

It is two linked iodinated tyrosine molecules (cleaved from large glycoprotein prohormone, thyroglobulin)

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7
Q

Are thyroid hormones hydrophobic or hydrophilic?

A

They are hydrophobic peptide hormones, require blood binding proteins to travel in circulation and the receptors are nuclear receptors

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8
Q

What is deiodinase?

A

Enzyme that catalyzes the removal of an iodine –> this can be activating or deactivating

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9
Q

What is the primary hormone secreted from the thyroid gland?

A

Secretes thyroxine (T4), and a small amount of T3.

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10
Q

What is T3?

A

Arises from deiodination of the outer ring of T4, mostly in peripheral tissues (liver, kidney, muscle). It has the highest binding affinity for the nuclear TH receptors –> most metabolically active form

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11
Q

What is reverse T3 (rT3)?

A

It arises from deiodination of the inner ring of T4, has a very short half-life, doesn’t have any genomic effects

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12
Q

How many deiodinase enzymes are there?

A

3, differ in tissue localization and substrate specificity, enable local modulation of TH acitions

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13
Q

What are the thyroid glands made up of?

A

Small globular sacs (follicles) that are filled with colloid

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14
Q

What are follicular cells?

A

They line the follicles and synthesize thyroglobulin and take up iodide

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15
Q

What occurs at the apical-colloid surface of follicular cells?

A

Iodine is oxidized, and thyroglobulin is iodinated as it is secreted into the colloid, where it is stored until needed. When needed (stimulated by TSH), colloid contents are engulfed by neighbouring follicle cells, which is where cleavage of thyroglobulin in lysosomes produces T3 and T4, which are released into circulation

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16
Q

What are the steps of thyroid hormone synthesis?

A
  1. Iodine is uptaken through active transport across the basement membrane, iodine is oxidized so that it can attach to TG
  2. (in parallel) transcription of TG gene (promoted by TSH)
  3. translation and modulation of TG prohormone
  4. packaging of TG by golgi
  5. Secretion of TG into the colloid by exocytosis at apical surface of cells
  6. Production of iodinated TG at apical-colloid interface. Tyrosines are iodinated, and two iodinated tyrosyl residues in TG are joined
  7. TG with iodinated tyrosines are filled with colloid
  8. When stimulated by TSH, TG is reabsorbed. Lysosomes fuse with the endosomes and TG is degraded, T4 and T3 are released into circulation
17
Q

What are the cells in the pituitary that release TSH?

A

Thyrotroph cells

18
Q

What is TSH?

A

It is a glycoprotein that stimulates thyroid gland function.

19
Q

What stimulates TSH release?

A

Stimulated by thyrotropin-releasing hormone (TRH) from the hypothalamus

20
Q

What inhibits release/production of thyroid hormone?

A

Somatostatin, also inhibited by thyroid hormone in a negative feedback loop –> inhibits TRH and TSH, excess iodide inhibits TH production

21
Q

How does thyroid hormone exert its effects?

A
  1. Genomic actions (bind to nuclear receptors and regulate gene expression)
  2. Non-genomic actions (interacting with enzymes and other cellular proteins)
22
Q

What is the structure of TH receptors?

A

They have an amino terminal domain, a DNA binding domain, and a ligand binding domain at C terminus. This has the highest affinity for T3. These are not bound to heat shock proteins, they stay bound to DNA.

23
Q

Where does the thyroid hormone receptor bind in the DNA?

A

Bind response elements (TRE) as a heterodimer, preferentially with the retinoic X receptor (RXR); interaction with TH causes a conformational change, which activates or suppresses target genes

BIOL432: Molecular Endocrinology (12 decks)

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