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Thyroid-Stimulating Hormone: Biosynthesis, Cell Biology, and Bioactivity

Michael Reese Hospital, University of Illinois Chicago, Illinois 60616

Correspondence: Address requests for reprints to: Dr. James Magner, Michael Reese Hospital, 2816 South Ellis 216 RC, Chicago, Illinois 60616.

Abstract

Introduction: THYROID-stimulating hormone is a 28,000 dalton, pituitary-derived glycoprotein that is composed of two noncovalently linked subunits, and β. TSH is chemically related to the pituitary gonadotropins, LH, and FSH, and to placental CG. TSH is synthesized by thyrotropes of the anterior pituitary and stored in secretory granules; it is released into the circulation in a regulated manner, binds to thyroid cells, and activates them to release thyroid hormones.

Smith (1) and Allen (2) performed experiments in the early 20th century suggesting that the pituitary contained a thyrotropic substance. Subsequently the subunit structure of the glycoprotein hormones has been determined, and the amino acid sequences of TSH subunits from several species have been learned. In recent years great progress has been made in determining the structures of TSH and β-subunit genes and the chromosomal localizations and regulation of those genes. These advances have recently been reviewed by Shupnik et al. (3). The posttranslational processing events of TSH subunits have been learned in some detail, and the kinetics of the oligosaccharide processing and subcellular sites of subunit combination and processing have been studied. Investigations of the secretion, metabolic clearance, and bioactivity of TSH have demonstrated important biological roles for the TSH oligosaccharides. Although glycoprotein hormones have proved difficult to crystallize [deglycosylation may aid crystallization (4)], probable tertiary structures have been proposed, and use of monoclonal antibodies and other specialized techniques have allowed the function of domains of the subunits to be postulated.

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