L31. Physiology - Thyroid Physiology

The anterior pituitary hormone that regulates thyroid hormone production.

The hypothalamic hormone that regulates TSH release.

The thyroid gland requires iodine for the synthesis of thyroid hormones. This distinguishes it from other endocrine glands.

Thyroid hormone is stored within the thyroid gland in a protein-rich substance called colloid.

Thyroid hormone synthesis occurs in the follicular cells of the thyroid gland.

The active form of thyroid hormone, T3, is composed of two tyrosine rings connected with three iodine atoms.

Most of the secreted T4 (thyroxine) is ultimately converted to T3 in the circulation and within target cells.

Due to its hydrophobic nature, thyroid hormone is not immediately released after synthesis but is stored as a protein conjugate in colloid. This is different from most hydrophobic hormones.

A condition where the thyroid gland is enlarged, but produces normal levels of thyroid hormones. It is often caused by a lack of iodine in the diet.

A condition characterized by excessive thyroid hormone production and a wide range of symptoms including increased metabolism, nervousness, and bulging eyes.

A condition where the thyroid gland produces insufficient thyroid hormone, leading to a slower metabolism and various symptoms like weight gain, fatigue, and cold intolerance.

An autoimmune disorder where the body attacks its own thyroid gland, leading to hypothyroidism.

A condition where the body's cells are resistant to thyroid hormone, leading to hypothyroidism despite normal or even elevated thyroid hormone levels.

90 micrograms of T4 are secreted daily, compared to 1-2 micrograms of T3. T4 circulates at much higher levels (50-fold) than T3.

T4 can be converted to T3 (35%), reverse T3 (45%), or destroyed (10%).

80% of circulating T3 comes from conversion of T4, 20% comes directly from the thyroid.

More than 99% of T3 and T4 in circulation are bound to carrier proteins, mainly thyroxine binding globulin (TBG), thyroxine binding prealbumin (transthyretin), and albumin.

Only a small fraction (0.1% for T4 and 0.5% for T3) of thyroid hormone in circulation is free.

Protein-bound T3 and T4 serve as a reservoir of thyroid hormone in circulation, with a longer half-life than free hormone.

Thyrotropin-releasing hormone (TRH) is released from the hypothalamus.

TRH travels via portal veins to the anterior pituitary, where it binds to receptors on thyrotrophs.

TSH (thyroid stimulating hormone) is released from the anterior pituitary.

TSH stimulates follicular cells in the thyroid to produce and release T3 and T4.

Thyroid cells actively transport iodide (I-) against a concentration gradient using the sodium-iodide symporter (NIS).

The pendrin transporter moves iodide from the follicular cell into the lumen, where it is converted to iodine by thyroid peroxidase.

Thyroid peroxidase (TPO) catalyzes the conversion of iodide to iodine and attaches it to tyrosine residues within thyroglobulin.

Thyroid peroxidase (TPO) links iodinated tyrosine residues to form DIT (diiodothyronine) or MIT (monoiodothyronine).

Thyroglobulin, a protein containing iodinated tyrosine residues, is taken into the follicular cells by endocytosis.

Within lysosomes, thyroglobulin is broken down by proteolytic enzymes, releasing T3, T4, MIT, DIT, and other amino acids.

MIT and DIT are deiodinated, and the resulting iodide and amino acids are recycled back into thyroglobulin synthesis.

The thyroid hormone T4 is converted to the active form T3 in the follicular cell by a deiodinase enzyme.

TSH (thyroid-stimulating hormone) regulates the production of T3 and T4, stimulating all steps (except conjugation) and promoting growth of follicular cells.

T3 and T4 are released from the thyroid follicular cells into the bloodstream, where they circulate and exert their effects on various tissues and organs.

Thyrotropin-releasing hormone (TRH) is a key regulator of thyroid function. It is released from neurons in the hypothalamus (specifically in the arcuate nucleus (ARN) and the median eminence (ME)) and travels through the portal veins to the anterior pituitary.

TRH binds to a G protein-coupled receptor (GPCR) on thyrotrophs, the cells in the anterior pituitary that produce thyroid-stimulating hormone (TSH). This binding activates two signaling pathways: DAG-PKC pathway and PLC/IP3 pathway. These pathways ultimately lead to increased protein phosphorylation and calcium release from intracellular stores.

The increased calcium release and phosphorylation cascades, triggered by TRH binding to thyrotrophs, stimulate the synthesis and release of thyroid-stimulating hormone (TSH).

TSH travels to the thyroid gland and binds to receptors on follicular cells. This binding stimulates the follicular cells to synthesize and release thyroid hormones (T3 and T4).

The thyroid hormones, T3 and T4, play a vital role in negative feedback regulation of their own production. They act on both the thyrotrophs in the pituitary and the TRH-secreting neurons in the hypothalamus, reducing the production of both TSH and TRH respectively. This mechanism helps maintain optimal levels of thyroid hormones in the body.

Somatostatin, a hormone released from the hypothalamus, can inhibit the release of TSH from thyrotrophs. This creates a new setpoint for thyroid hormone release, often leading to lower thyroid hormone levels.

Dopamine also has a role in regulating thyroid hormone release. It inhibits the activity of thyrotrophs, similar to somatostatin, and helps maintain a balance in thyroid hormone production.

Once T4 enters the cell, it is converted into T3 by a cytoplasmic enzyme called 5'/3'-monodeiodinase. This conversion results in nearly equal levels of T4 and T3 inside the cell.

The thyroid hormone receptor (TR) is a nuclear receptor that binds to DNA at specific regions called thyroid response elements (TREs) in the promoter regions of genes. This binding regulates the transcription of these genes, ultimately controlling the production of various proteins involved in various cellular processes.

T3 has a higher affinity for the TR compared to T4, and more T3 is free (not protein bound) in circulation. These factors contribute to T3 being more biologically active than T4. The TR binds to DNA as a heterodimer, forming a complex with the retinoid X receptor (RXR).