Journal of Glycobiology
Open Access

Influence of glycans on biological activities of pituitary gonadotropins, follicle-stimulating hormone and luteinizing hormone

Glycobiology World Congress

August 10-12, 2015 Philadelphia, USA

George R Bousfield

Scientific Tracks Abstracts: J Glycobiol

Abstract :

The gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play central roles in the control
of reproduction by connecting neuroendocrine hypothalamic/pituitary activities to gonadal function. LH and FSH
receptor activation is an important part of assisted reproductive technologies, such as in vitro fertilization. Both FSH and
LH are heterodimeric glycoproteins, each composed of a non-covalently associated common α- and a hormone-specific
β-subunit. Both subunits are N-glycosylated. Although high affinity binding of both hormones to their cognate receptors
occurs exclusively by protein-protein interactions, full gonadotropin receptor activation involves N-linked glycans. However,
the activation mechanism remains elusive. Part of the problem is the high degree of oligosaccharide micro heterogeneity
that challenges even contemporary analysis by high-resolution mass spectrometry. LH possesses three N-glycosylation sites
that are always occupied by glycans and can be removed individually, permitting characterization in a site-specific manner.
While FSH glycopeptides can be obtained from all 4 potential N-glycosylation sites, only 2 can be thoroughly analyzed by
glycopeptide mass spectrometry. Even then, only about a third of the glycan population can be detected. While both FSHα
sub-unit glycosylation sites can be interrogated individually by sequential peptide-N-glycanase digestion, both FSHβ glycans
are released simultaneously. This is unfortunate, because naturally occurring forms of FSH lacking either one of the 2 FSHβ
N-glycans bind their receptors more rapidly, occupy more FSH binding sites, and provoke a more robust cellular response
thanfully-glycosylated FSH. Moreover, the ratio of FSH glycosylation variants may be under physiological regulation.

Biography :

George R Bousfield completed his PhD at Indiana University in 1981. He then pursued Postdoctoral studies at the University of Texas, M D Anderson Cancer
Center with Darrell Ward. He is currently the L M Jones Distinguished Professor in the Fairmount College of Liberal Arts and Sciences at Wichita State University
and Director of the WSU Protein Core Facility. He has published more than 56 journal articles.