![]() The beta subunit confers specificity to the molecule since it interacts with the TSH receptor (TSH-R) expressed on the basolateral membrane of thyroid follicular cells, and is rate-limiting in the formation of the mature heterodimeric protein. The alpha subunit (glycoprotein hormones, alpha polypeptide) is common to TSH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and chorionic gonadotropin (CG). While the molecular weight of the deduced amino-acid sequence of the mature alpha and beta subunits in combination is approximately 28,000 Da, additional carbohydrate (15% by weight) results in a significantly higher molecular weight estimate based on sizing by polyacrylamide gel electrophoresis. TSH is a heterodimer consisting of an alpha and a beta subunit that are tightly, but non-covalently, bound ( 1, 2). For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, The TSH Molecule The second deals with physiological studies in humans which serve as the background for the diagnostic use of TSH measurements and reviews the results of TSH assays in pathophysiological disorders. The first portion reviews basic studies of TSH synthesis, post-translational modification, and release. This chapter is organized into two general sections. The utility of TSH measurements has been recognized and its use has remarkably increased due to the development of immunometric methodologies for its accurate quantitation in serum, although the criteria to define a “normal range” still remain a matter of controversy. This regulation is so carefully maintained that an abnormal serum TSH in most patients is believed to indicate the presence of a disorder of thyroid gland function. ![]() ![]() The consequence of the dynamic interplay of these two dominant influences on TSH secretion, the positive effect of TRH on the one hand and the negative effects of thyroid hormones on the other, results in a remarkably stable morning concentration of TSH in the circulation and consequently little alteration in the level of circulating thyroid hormones from day to day and year to year. Those factors are reviewed in this chapter and consist principally of thyrotropin-releasing hormone (TRH) and the feedback effects of circulating thyroid hormones at the hypothalamic and pituitary levels. Thus, regulation of thyroid function in normal individuals is to a large extent determined by the factors which regulate the synthesis and secretion of TSH. ![]() ![]() In the absence of the pituitary or of thyrotroph function, hypothyroidism ensues. The activity of the thyroid gland is predominantly regulated by the concentration of the pituitary glycoprotein hormone, thyroid-stimulating hormone (TSH). ![]()
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