Role of Glycosylation in Function of Follicle-Stimulating Hormone

Abstract

The oligosaccharide structures of heterodimeric glycoprotein hormones, such as follicle-stimulating hormone (FSH), have been shown to play an important role in the biosynthesis, secretion, metabolic fate, and regulation of potency of the hormone. The oligosaccharide structures attached to each subunit of the protein seem to exhibit distinct roles in some of these functions. Glycans attached to the alpha-subunit are critical for dimer assembly, integrity, and secretion, as well as for signal transduction; although beta-subunit glycans are also important for dimer assembly and secretion, they play a crucial role in clearance of the dimer from the circulation. Alternative glycosylation on FSH and other glycoprotein hormones not only may affect the metabolic clearance and net in vivo biopotency of the hormone, but also offers the interesting possibility that some glycosylation variants of the hormone may provoke differential or even unique effects at the target cell level. Glycosylation of FSH is regulated by hypothalamic and/or end products from the glands under the control of this hormone. In particular, estrogens regulate terminal sialylation and thus some functional properties of the gonadotropin influenced by sialic acid. Through these extrapituitary inputs, the gonadotroph may regulate not only the amount but also the intensity of the gonadotropin signal to be secreted by the pituitary in a given physiological condition.

Biological activities of recombinant Manchurian trout FSH and LH: their receptor specificity, steroidogenic and vitellogenic potencies

“…Together, with thyrotropin (TSH) and chorionic gonadotropin (CG), GTHs are members of the glycoprotein hormone family and each member is a heterodimer consisting of two subunits termed a and b (Pierce & Parsons 1981, Suzuki et al 1988a, Swanson et al 2003. These heterodimeric glycoproteins are reported to carry highly conserved glycosylation sites, and the attached oligosaccharides are related to the hormone's biosynthesis, half-life, and biological activity both in fishes as well as in mammals (Ulloa-Aguirre et al 1999, Zenkevics et al 2000, Klein et al 2003. These hormones react to specific receptors at the reproductive organs which is an essential requirement for their physiological action (Simoni et al 1997, Dufau 1998, Kumar & Trant 2001, Bogerd et al 2005.…”

Recent Advances in Glycosylation Modifications in the Context of Therapeutic Glycoproteins

“…Although glycosylation is not essential for INFs protein efficacy or safety, lack of glycosylation decreases their biological activity and circulatory half-life. Oligosaccharide structures of follicle-stimulating hormone heterodimer play an important role in its biosynthesis, secretion, metabolic fate, and functional potency (Ulloa-Aguirre et al 1999). The glycans at each subunit seem to exhibit distinct roles, with those in subunit critical for dimer assembly, signal transduction, and secretion, and those in subunit more crucial for circulation clearance.…”

Genetics of GNE myopathy in the non-Jewish Persian population

“…11 In addition, sialic acids play important roles in determining the survival time and biologic activity of various glycoproteins, hormones, and enzymes, in vivo. 12 The GNE gene, located on chromosome 9p12-13 is~62.6 kb and consists of 13 exons encoding multiple GNE protein isoforms, its longest consisting of 753 amino acids. GNE is expressed in almost all body tissues but the highest expression has been observed in the liver.…”

“…GNE is expressed in almost all body tissues but the highest expression has been observed in the liver. 9,12 Interestingly, the tissues with the highest GNE expression, including liver, lung, and kidney, remain intact in GNE myopathy and the disease selectively affects skeletal muscles, which have relatively low levels of the enzyme. 13 In the mouse, GNE is expressed very early and during all stages of development.…”