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dc.contributor.authorJiang, Chao
dc.contributor.authorHou, Xiaoying
dc.contributor.authorWang, Cheng
dc.contributor.authorMay, Jeffrey V.
dc.contributor.authorButnev, Viktor Y.
dc.contributor.authorBousfield, George R.
dc.contributor.authorDavis, John S.
dc.identifier.citationJiang, Chao; Hou, Xiaoying; Wang, Cheng; May, Jeffrey V.; Butnev, Viktor Y.; Bousfield, George R.; Davis, John S. 2015. Hypoglycosylated hFSH has greater bioactivity than fully glycosylated recombinant hFSH in human granulosa cells. Journal of Clinical Endocrinology & Metabolism, vol. 100:no. 6:pp E852-E860en_US
dc.descriptionClick on the DOI link to access the article (may not be free).en_US
dc.description.abstractContext: Previous studies suggest that aging in women is associated with a reduction in hypoglycosylated forms of FSH. Objective: Experiments were performed to determine whether glycosylation of the FSH beta subunit modulates the biological activity of FSH in human granulosa cells. Design and Setting: Recombinant human FSH (hFSH) derived from GH(3) pituitary cells was purified into fractions containing hypoglycosylated hFSH(21/18) and fully glycosylated hFSH(24). The response to FSH glycoforms was evaluated using the well-characterized, FSH-responsive human granulosa cell line, KGN at an academic medical center. Interventions: Granulosa cells were treated with increasing concentrations of fully-or hypoglycosylated FSH glycoforms for periods up to 48 hours. Main Outcome Measure(s): The main outcomes were indices of cAMP-dependent cell signaling and estrogen and progesterone synthesis. Results: We observed that hypoglycosylated FSH21/18 was significantly more effective than fully glycosylated FSH24 at stimulating cAMP accumulation, protein kinase A (PKA) activity, and cAMP response element binding protein (CREB) (S133) phosphorylation. FSH21/18 was also much more effective than hFSH(24) on the stimulation CREB-response element-mediated transcription, expression of aromatase and STAR proteins, and synthesis of estrogen and progesterone. Adenoviral-mediated expression of the endogenous inhibitor of PKA, inhibited FSH21/18- and FSH24-stimulated CREB phosphorylation, and steroidogenesis. Conclusions: Hypoglycosylated FSH21/18 has greater bioactivity than fully glycosylated hFSH24, suggesting that age-dependent decreases in hypoglycosylated hFSH contribute to reduced ovarian responsiveness. Hypoglycosylated FSH may be useful in follicle stimulation protocols for older patients using assisted reproduction technologies.en_US
dc.description.sponsorshipThis work was supported by NIH 1P01 AG029531, the VA Medical Center, and the fOlson Center for Women's Health, Department of Obstetrics and Gynecology at the University of Nebraska Medical Center.en_US
dc.publisherEndocrine Societyen_US
dc.relation.ispartofseriesJournal of Clinical Endocrinology & Metabolism;v.100:no.6
dc.subjectOvarian stimulationen_US
dc.subjectGlycan structureen_US
dc.subjectFSH isoformsen_US
dc.titleHypoglycosylated hFSH has greater bioactivity than fully glycosylated recombinant hFSH in human granulosa cellsen_US
dc.rights.holder© 2015 Endocrine Societyen_US

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