In vivo and in vitro impact of carbohydrate variation on human follicle-stimulating hormone function

Loading...
Thumbnail Image
Authors
Bousfield, George R.
May, Jeffrey V.
Davis, John S.
Dias, James A.
Kumar, T. Rajendra
Advisors
Issue Date
2018-05-09
Type
Article
Keywords
Pituitary , N-glycosylation , Follicle-stimulating hormone , Bone , Female Infertility
Research Projects
Organizational Units
Journal Issue
Citation
Bousfield GR, May JV, Davis JS, Dias JA and Kumar TR (2018) In Vivo and In Vitro Impact of Carbohydrate Variation on Human Follicle-Stimulating Hormone Function. Front. Endocrinol. 9:216
Abstract

Human follicle-stimulating hormone (FSH) exhibits both macro-and microheterogeneity in its carbohydrate moieties. Macroheterogeneity results in three physiologically relevant FSH beta subunit variants, two that possess a single N-linked glycan at either one of the two beta L1 loop glycosylation sites or one with both glycans. Microheterogeneity is characterized by 80 to over 100 unique oligosaccharide structures attached to each of the 3 to 4 occupied N-glycosylation sites. With respect to its receptor, partially glycosylated (hypoglycosylated) FSH variants exhibit higher association rates, greater apparent affinity, and greater occupancy than fully glycosylated FSH. Higher receptor binding-activity is reflected by greater in vitro bioactivity and, in some cases, greater in vivo bioactivity. Partially glycosylated pituitary FSH shows an age-related decline in abundance that may be associated with decreased fertility. In this review, we describe an integrated approach involving genetic models, in vitro signaling studies, FSH biochemistry, relevance of physiological changes in FSH glycoform abundance, and characterize the impact of FSH macroheterogeneity on fertility and reproductive aging. We will also address the controversy with regard to claims of a direct action of FSH in mediating bone loss especially at the peri-and postmenopausal stages.

Table of Contents
Description
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Publisher
Frontiers Media S.A.
Journal
Book Title
Series
Front. Endocrinol;v.9
PubMed ID
DOI
ISSN
1664-2392
EISSN