Thyroid hormones

What does the thyroid gland produce

T3 (triiodothyronine) and T4 (thyroxine)

These regulate metabolism, growth and development

Thyroid follicles

Consists of follicular cells surrounding a lumen filled with colloid

Colloid is composed of thyroglobulin (precursor of T3 and T4)

Follicular cells - synthesize thyroglobulin + secrete it in colloid

Parafollicular cells (C-cells) - secrete calcitonin (regulate calcium homeostasis bu lowering blood calcium levels)

Triiodothyronine (T3)

More biologically active, has 3 iodine atoms, shorter half life

Has higher affinity for nuclear receptors

Thyroxine (T4)

Less active but more abundant, has 4 iodine atoms, T4 is converted into T3 peripheral tissues by deiodinase enzymes

Acts as prohormone → is converted to T3 in tissues

Essential molecules for thyroid hormone synthesis

Tyrosine - part of thyroglobulin, acts as backbone onto which iodine is added

Iodine - obtained from diet, essential for hormone formation

Collection and concentration of iodide

Iodide is transported from bloodstream to thyroid follicular cells via sodium-iodide symporter (NIS)

Then it is moved into the colloid by pendrin transporter

Oxidation and iodination

Inside the colloid, iodide is oxidised to iodine by enxyme thyroid peroxidase

Iodine is attached to tyrosine residues in thyroglobulin to form MIT, DIT

MIT (monoiodotyrosine) - 1 iodine, DIT (diiodotyrosine) - 2 iodines

Attachment

2 iodinated tyrosines are coupled together, and are catalysed by TPO

DIT + DIT → T4, DIT + MIT → T3

Hormones are still bound to thryoglobulin and stored in colloid

Secretion

When TSH stimulates thyroid, iodinated thyroglobulin is endocytosed back into the follicular cells

Lysosomes digest thyroglobulin and release T3 and T4 into circulation

MIT and DIT that are not coupled are deiodinated and recycled

Action

T3 and T4 enter target cell

Deiodinase converts T4 into T3, in cytoplasm, as it is more active

T3 enters the nucleus, binds to thyroid receptors already attached to DNA

When bound, it activates or represses the transcription of specific genes

mRNA is produced, leading to synthesis of proteins that change cell function

Main binding proteins in plasma

Thyroxine-binding globulin - major carrier of T$ and T3, high affinity

Transthyretin - binds T4 more than T3

Albumin - binds large amounts but with weak affinity

Actions of thyroid hormones

Stimulate transcription of GH and PRL genes in pituitary

T3 enhances GH receptor expression in target tissues like bone and muscles

Increases absorption of glucose from digested food (glucose transporters)

Increases number of mitochondria → boosts ATP production

T3 increases beta-adrenergic receptors which makes them more sensitive to epinephrine

Thyroid hormone effect on protein synthesis

Normal levels - T3 and T4 stimulate ribosomes and activate genes that tell the cell to make proteins, supports growth, tissue repair and muscle building

High levels - body metabolism speeds up → needs more energy, it starts breaking down muscle proteins to use amino acids for glucose production

Thyroid hormone effect on carbohydrates

Low levels - favour the storage of glucose as glycogen, promotes energy storage

High levels - rapid breakdown of glycogen, make glucose from amino acids…

T3 major target - Na+/K+ ATPase pump

When more pumps are made, more ATP is consumed to keep them working

higher ATP demand → higher metabolic rate (because pumps need energy, cells consume more glucose and oxygen to produce more ATP)

Thyroid hormones actions → increase oxygen consumption

Thyroid hormone actions on the cardiovascular system

Thyroid hormone action on the respiratory system

Thyroid hormone action on renal system

Thyroid hormone action on oxygen carrying capacity

Thyroid hormone action on growth and tissue development

Thyroid hormone action on nervous system

Thyroid hormone action on reproductive system

Hyperthyroidism

Low thermogenesis - fewer Na+/K+ pumps → less mitochondrial activity→ less ATP use and heat production

Skin/hair - dry skin, rat tail, hyperpigmentation, symmetric alopecia

Behaviour - lethargy, drowsiness, mental dullness

Weight - weight gain, metabolism slows down → energy stored as fat

Cardiovas - lower heart rate due to reduced stim of b-adrenergic receptors

Blood - bone marrow doesnt produce enough RBC (low metabolism)

Cretinism - in puppies, stunt in physical and mental development

Goitre - by iodine deficiency of TSH overstim → enlarged thyroid gland

Hyperthyroidism

Weight - weight loss, increased appetite, excessive metabolism

Muscles - protein catabolism increases, muscles shrink and weaken

Cholesterol - enhanced lipid metabolism → low cholesterol

Heat - heat production by increased ATP and mitochondrial activity

Cardiopulm - increased heartrate and breathing rate (panting, hypertension and murmurs)

Erythrocytosis - increased RBC

Neuromuscular - tremors, agitation, twitches, stimulation of NS

Goitre - enlarged thyroid