In Vivo and In Vitro Impact of Carbohydrate Variation on Human Follicle-Stimulating Hormone Function
Human follicle-stimulating hormone (FSH) exhibits both macro- and microheterogeneity in its carbohydrate moieties. Macroheterogeneity results in three physiologically relevant FSHβ subunit variants, two that possess a single N-linked glycan at either one of the two βL1 loop glycosylation sites or on...
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fendo.2018.00216/full |
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| author | George R. Bousfield Jeffrey V. May John S. Davis John S. Davis John S. Davis James A. Dias T. Rajendra Kumar |
| author_facet | George R. Bousfield Jeffrey V. May John S. Davis John S. Davis John S. Davis James A. Dias T. Rajendra Kumar |
| author_sort | George R. Bousfield |
| collection | DOAJ |
| description | Human follicle-stimulating hormone (FSH) exhibits both macro- and microheterogeneity in its carbohydrate moieties. Macroheterogeneity results in three physiologically relevant FSHβ subunit variants, two that possess a single N-linked glycan at either one of the two βL1 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 (hypo-glycosylated) 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. |
| first_indexed | 2024-12-13T06:07:01Z |
| format | Article |
| id | doaj.art-52233f27874347be845f7a1b63d3c981 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-13T06:07:01Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-52233f27874347be845f7a1b63d3c9812022-12-21T23:57:11ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-05-01910.3389/fendo.2018.00216368677In Vivo and In Vitro Impact of Carbohydrate Variation on Human Follicle-Stimulating Hormone FunctionGeorge R. Bousfield0Jeffrey V. May1John S. Davis2John S. Davis3John S. Davis4James A. Dias5T. Rajendra Kumar6Department of Biological Sciences, Wichita State University, Wichita, KS, United StatesDepartment of Biological Sciences, Wichita State University, Wichita, KS, United StatesDepartment of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE, United StatesDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, United StatesNebraska-Western Iowa Health Care System, Omaha, NE, United StatesDepartment of Biomedical Sciences, School of Public Health, University at Albany, Albany, NY, United StatesDepartment of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesHuman follicle-stimulating hormone (FSH) exhibits both macro- and microheterogeneity in its carbohydrate moieties. Macroheterogeneity results in three physiologically relevant FSHβ subunit variants, two that possess a single N-linked glycan at either one of the two βL1 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 (hypo-glycosylated) 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.http://journal.frontiersin.org/article/10.3389/fendo.2018.00216/fullpituitaryN-glycosylationfollicle-stimulating hormonebonefemale Infertility |
| spellingShingle | George R. Bousfield Jeffrey V. May John S. Davis John S. Davis John S. Davis James A. Dias T. Rajendra Kumar In Vivo and In Vitro Impact of Carbohydrate Variation on Human Follicle-Stimulating Hormone Function Frontiers in Endocrinology pituitary N-glycosylation follicle-stimulating hormone bone female Infertility |
| title | In Vivo and In Vitro Impact of Carbohydrate Variation on Human Follicle-Stimulating Hormone Function |
| title_full | In Vivo and In Vitro Impact of Carbohydrate Variation on Human Follicle-Stimulating Hormone Function |
| title_fullStr | In Vivo and In Vitro Impact of Carbohydrate Variation on Human Follicle-Stimulating Hormone Function |
| title_full_unstemmed | In Vivo and In Vitro Impact of Carbohydrate Variation on Human Follicle-Stimulating Hormone Function |
| title_short | In Vivo and In Vitro Impact of Carbohydrate Variation on Human Follicle-Stimulating Hormone Function |
| title_sort | in vivo and in vitro impact of carbohydrate variation on human follicle stimulating hormone function |
| topic | pituitary N-glycosylation follicle-stimulating hormone bone female Infertility |
| url | http://journal.frontiersin.org/article/10.3389/fendo.2018.00216/full |
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