Thyroid gland stimulation

Factors controlling calcium homeostasis are calcitonin, parathyroid hormone(PTH), and a vitamin D metabolite. Calcitonin, a polypeptide of 32 amino acid residues, mol wt - SGOO, is synthesized by the thyroid gland. Release is stimulated by small increases in blood Ca " concentration. The sites of action of calcitonin are the bones and kidneys. Calcitonin increases bone calcification, thereby inhibiting resorption. In the kidney, it inhibits Ca " reabsorption and increases Ca " excretion in urine. Calcitonin operates via a cyclic adenosine monophosphate (cAMP) mechanism. 

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

Lithium is concentrated in the thyroid gland and can impair thyroid hormone synthesis. Although goiter is uncommon, as many as 30% of patients develop at least transiently elevated thyroid-stimulating hormone values. Lithium-induced hypothyroidism is not usually an indication to discontinue the drug. Patients can be supplemented with levothyroxine if continuation of lithium is desired.30... 

On the other hand, some receptors are truly promiscuous in that they can activate two or more G-proteins from quite different classes, even in their normal cellular environment. For example, similar concentrations of thyroid-stimulating hormone (TSH 0.1-100 U/ml) can stimulate the incorporation of 32P-GTP into a, aQ, a12, a13, as, and aq/11 through activation of the thyrotropin receptor in membranes from human thyroid gland. TRH activation of Ca2+ currents in GH3 cells is obtunded equally by antisense-depletion of l2, aa, and aq/11, but not of aQ. Some individual genotypic P2y nucleotide receptors can also couple with equal affinity to PTx-sensitive and PTx-insensitive G-proteins in sympathetic neurons. The degree, or otherwise, of such promiscuity is presumably determined by the structure of the receptor protein itself. 

An alternative therapeutic approach to osteoporosis is through the use of calcitonin (798), a peptide hormone containing 32 amino acids (the sequence is species dependent) secreted by the thyroid gland, which stimulates the production of new bone. Synthetic calcitonins corresponding to human, eel, and salmon variants, and natural calcitonin extracted from pig thyroid, are all used in medicine - they have slightly different efficacies, side effects, and tolerance levels (799). 

Demonstration that the effects of thyrotoxicosis or goiter are due to an excess or deficiency in (thyroxine + T3) secretion does not explain how the diseases originate nor why development and metabolic rate are affected. It is thought that some cases of thyrotoxicosis (Graves disease) may be caused by abnormal immune responses mimicking the effects of thyroid-stimulating hormone on the thyroid gland. 

When the thyroid gland is stimulated to secrete thyroxine, a small piece of iodinated Tgb is taken from the lumen into a follicular cell, where the hormones are released from the protein. Both T3 and T4 are secreted from the vesicle directly into the bloodstream but the plasma concentration of T4 is substantially higher than that of T3. In contrast, T3 has a higher biological activity than T4 and conversion of T4 to T3 occurs at the target site. 

In another factor related to the thyroid gland, wide variation has been observed with respect to the thyroid-stimulating hormone (TSH) of the pituitary. D Angelo8 and co-workers, using tadpoles as a tool, have studied the thyroid and TSH activity of the serums of normal and diseased individuals. Both limb growth (metamorphosis) induced by thyroid hormone and the development of thyroid tissue induced by TSH were measured. 

A deficiency of iodine results iu insufficient synthesis of thyroxine and a low plasma level, so that secretion of TSH is increased in an attempt to stimulate synthesis but this results in enlargement of the thyroid gland (goitre). Iodine deficiency in pregnancy impairs brain development in the foetus, causing mental retardation (known as cretinism). Indeed iodine deficiency is one of the major public health issues worldwide an estimated 200 million people are affected. 

Thyrotropin (thyroid-stimulating hormone, TSH) and the related hormones lutropin (luteinizing hormone, LH) and follitropin (follicle-stimulating hormone, FSH) originate in the adenohypophysis. They are all dimeric glycoproteins with masses of around 28 kDa. Thyrotropin stimulates the synthesis and secretion of thyroxin by the thyroid gland. 

Hypothyroidism Hypothyroidism may occur with long-term lithium administration. Patients may develop enlargement of thyroid gland and increased thyroid-stimulating hormone levels. 

TSH, or thyrotropin, is a glycosylated protein of two subunits, a and p. TSH stimulates the thyroid gland to produce thyroid hormones. Deficiencies are treated by giving thyroxine itself rather than TSH, but TSH is available for diagnostic purposes to differentiate between pituitary and thyroid gland failure as causes of hypothyroidism (see Chapter 65). 

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