The role of the asparagine-linked oligosaccharides of the alpha-subunit in human thyrotropin bioactivity

Endocrinology
F FaresZ Kraiem

Abstract

TSH and the gonadotropins (FSH, LH, and hCG) are a family of heterodimeric proteins that share a common alpha-subunit and differ in their hormone-specific beta-subunit. The asparagine-linked (N-linked) oligosaccharides on these hormones are important in signal transduction. The N-linked oligosaccharides on the alpha-subunit have no effect on hCG and hFSH receptor binding, but are critical for their biological activity. Here, we analyzed the role of alpha-subunit N-linked oligosaccharides in human TSH (hTSH) bioactivity by site-directed mutagenesis and gene transfer. This was achieved by mutating the asparagine (Asn) residue in the N-linked glycosylation consensus sequence (Asn-X-Thr/Ser) to aspartic acid. The wild-type hTSH and its variants were expressed in Chinese hamster ovary cells. Wild-type alpha-subunit and its mutants (alpha 1, alpha 2, and alpha(1 + 2)) were efficiently combined with TSH beta-subunit and secreted as dimers. The bioactivity of TSH glycosylation variants was determined by measuring their abilities to stimulate cAMP formation and T3 secretion using a serum-free culture system of human thyroid follicles. Using this system, wild-type hTSH was significantly effective in the stimulation of cAMP formation and ...Continue Reading

Citations

Oct 7, 2015·Frontiers in Endocrinology·Selvaraj G NatarajaStephen S Palmer
Feb 12, 1998·Thyroid : Official Journal of the American Thyroid Association·Z KraiemB C Nisula
Jul 10, 2018·Endocrine Reviews·Ross C AndersonRobert P Millar
Aug 18, 2018·Thyroid Research·Bryce C SimesChukwuma M Okoroji
Nov 18, 2000·The Journal of Biological Chemistry·F A FaresZ Kraiem
Apr 4, 2021·Pharmaceutics·Naiel AzzamFuad Fares

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