The thyroid gland, which is located at the base of the neck, consists of two lateral lobes connected by an isthmus. On a microscopic level, it is made up of follicles, which in turn are made up of follicular cells surrounding a lumen, which is where thyroglobulin (thyroid hormone precursor) is stored. On the outside of the follicles are C-cells, which secrete calcitonin (see here for more information on calcitonin). The thyroid has a high blood supply to allow hormones to be readily secreted into circulation.
Explain the synthesis & secretion of thyroid hormones
Thyroid hormones come in two flavours: thyroxine (T4) and triiodothyronine (T3). Both are derived from tyrosine (as are dopamine and adrenaline). T4 is more common than T3, making up around 90% of the thyroid hormones released. However, T3 is more potent. T4 can be converted into T3 by de-iodination of the outer ring. If the inner ring is de-iodinated, as may occur during stress, then rT3 (reverse T3) is formed, which is inactive.
The main "ingredients" needed to synthesise thyroid hormones are iodine and thyroglobulin (which, as mentioned above, is a precursor for T3 and T4). Thyroglobulin is made by the follicular cells of the thyroid, whereas iodine is obtained from the diet. Absorption of iodine is poor, but it can be readily stored. In times of iodine deficiency, it can take a couple of months for symptoms to show.
Thyroid hormone synthesis kicks off by absorption of iodine. Iodine is transported into follicular cells via a Na+/I- symporter. It is then pumped out the other side and into the lumen via an I-/Cl- antiporter called Pendrin. At the same time, thyroglobulin is produced in the endoplasmic reticulum of follicular cells before being packaged in vesicles (along with peroxidase) and exocytosed into the lumen.
Once everything is in the lumen, I- is oxidised by that peroxidase that was packaged with the thyroglobulin. Tyrosine residues on thyroglobulin are then iodinated to form either diiodotyrosine (DIT) or monoiodotyrosine (MIT). Two DITs can combine to form T4, or one MIT and one DIT can combine to form T3.
After iodination has occurred, iodinated thyroglobulin is endocytosed by the follicular cells. It combines with lysosomes containing enzymes that cleave off T4, T3, MITs and DITs. Since MITs and DITs are non-functional, the iodine from these is removed and recycled. T4 and T3 then moves into the blood via an MCT (monocarboxylate transporter). Once in the blood, T4 and T3 are transported around by thyroxine-binding globulin (TBG), TTR/TBPA or albumin. When they get to their destination, they are brought into cells by MCTs. De-iodinases may then convert T4 to T3 with the help of tin and zinc.
Discuss the control of thyroid function
Throughout the day, we have a tonic basal release of TRH (thyrotropin-releasing hormone) from the hypothalamus. TRH stimulates release of TSH (thyroid-stimulating hormone) from the anterior pituitary. TSH then stimulates release of thyroid hormones from the thyroid. Control is by negative feedback- build-up of thyroid hormones downregulates TRH receptors in the anterior pituitary. There are also negative feedback effects on the hypothalamus, but to a lesser extent.
Aside from stimulating thyroid hormone synthesis and secretion, TSH also has other effects on the thyroid. It can cause hyperplasia and increase blood flow. This will become significant when talking about diseases involving the thyroid.
Discuss the effects of thyroid hormone on growth & metabolism
Thyroid hormone has effects across a range of different areas:
- General metabolic effects- increases basal metabolic rate by increasing the number and size of mitochondria, ATP production, VO2, active transport of ions, and heat production. Note that this means that without thyroid hormones, we produce less heat and therefore have cold intolerance (important in hypothyroidism).
- Carbohydrate metabolism- increases glucose absorption, glucose oxidation, gluconeogenesis, insulin secretion, and synthesis of specific metabolic enzymes.
- Lipid metabolism- increases lipolysis and lipogenesis, but has a stronger effect on lipolysis.
- Protein metabolism- can increase both protein synthesis and protein degradation.
- Skeletal system effects- increases bone formation (remember, thyroid hormones stimulate GH) and may play a role in bone maturation.
- CNS effects- thyroid hormones are essential for normal brain development.
- Cardiovascular effects- increases cardiac output, heart rate, contractility and tissue blood flow.
I've covered these in quite a bit of detail in an earlier post: Pituitary-Endocrine Axis Pathology. So I'm just going to list a few random fun facts that weren't covered in that earlier post.
- Deficiency of Pit-1, a transcription factor for TSH, can cause hypothyroidism
- Myxedema, which is oedema of the skin due to accumulation of polysaccharides (and water following by osmosis), is another potential symptom of hypothyroidism
- Bone and height defects in cretinism can be mostly reversed by thyroxine treatment, but this treatment has no effect on mental defects
- Methimazole is a drug used to treat Graves' disease. It lowers production of thyroid hormone
- Thyroid hormones are orally active, which means that if you eat something containing them, you can get a condition called thyrotoxicosis. This was the cause of "hamburger thyrotoxicosis" in the 1980s in USA (the patties were prepared from neck trimmings, but now such "gullet trimming" is banned).
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