The Regulation of Thyroid-stimulatinghormone Synthesis and Secretion: Molecular Biology and Biochemistry

The activity of the thyroid gland is predominantly regulated by the concentration of the pituitary glycoprotein hormone, thyroid-stimulating hormone (TSH). In the absence of pituitary or of thyrotroph function hypothyroidism ensues. 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. 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. 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, result 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. 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 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 matter of controversy. This chapter is organized into two general sections. The first portion reviews basic studies of TSH synthesis, post-translational modification and release. The second deals with physiological studies in humans which serve as the background to the diagnostic use of TSH measurements and reviews the results of TSH assays in a pathophysiological context. For complete coverage of this and all related areas of Endocrinology, please visit our online web-text, WWW.ENDOTEXT.ORG. THE REGULATION OF THYROID-STIMULATINGHORMONE SYNTHESIS AND SECRETION: MOLECULAR BIOLOGY AND BIOCHEMISTRY