@article{926f7e1fdb4a42f1940c77e017642dbd,
title = "Recombinant FSH glycoforms are bioactive in mouse preantral ovarian follicles",
abstract = "Female reproductive aging is characterized by a rise in follicle-stimulating hormone (FSH) levels during peri-menopause. N-linked glycans are co-translationally attached to the Asn7 and Asn24 residues on the FSHβ subunit. Differences in the number of N-glycans on the FSHβ subunit result in distinct glycoforms: hypo-glycosylated (FSH21/18, glycans absent on either Asn24 or Asn7, respectively) or fully-glycosylated (FSH24, glycans present on both Asn7 and Asn24). The relative abundance of FSH glycoforms changes with advanced reproductive age, shifting from predominantly FSH21/18 in younger women to FSH24 in older women. Previous in vitro studies in granulosa cell lines and in vivo studies using Fshb-null mice showed these glycoforms elicit differential bioactivities. However, the direct effects of FSH glycoforms on the mouse ovarian follicle have not yet been determined. In this study, we isolated secondary follicles from pre-pubertal mice and treated them with 20- or 100 ng/mL purified recombinant FSH glycoforms for 1 h or 18–20 h. Analysis of phosphorylated PKA substrates showed that glycoforms were bioactive in follicles following 1-h treatment, although differential bioactivity was only observed with the 100 ng/mL dose. Treatment of follicles with 100 ng/mL of each glycoform also induced distinct expression patterns of FSH-responsive genes as assessed by qPCR, consistent with differential function. Our results, therefore, indicate that FSH glycoforms are bioactive in isolated murine follicles.",
author = "Simon, {Leah E.} and Zhenghui Liu and Bousfield, {George R.} and Kumar, {T. Rajendra} and Duncan, {Francesca E.}",
note = "Funding Information: This work was supported in part by Northwestern University startup funds from the Department of Obstetrics and Gynecology (FED) and the Center for Reproductive Health After Disease (P50 HD076188) from the National Centers for Translational Research in Reproduction and Infertility, the Master of Science in Reproductive Science and Medicine Program, the Makowski Endowment Funds at the University of Colorado Anschutz Medical Campus and NIH funds (AG056046 to T R K and AG029531 to G R B and T R K). The authors acknowledge Dr Richard Schultz (Department of Biology, University of Pennsylvania) for his generous gift of the MSY2 primary antibody and Dr Irving Boime (Washington University School of Medicine) for a gift of recombinant human FSH. They also acknowledge Dr Teresa K Woodruff and Sarah Wagner (Northwestern University) for resource support and Dr Kelly Mayo and Dr Mary Ellen Pavone (Northwestern University) for their insightful discussions that have helped to advance this work. Funding Information: This work was supported in part by Northwestern University startup funds from the Department of Obstetrics and Gynecology (FED) and the Center for Reproductive Health After Disease (P50 HD076188) from the National Centers for Translational Research in Reproduction and Infertility, the Master of Science in Reproductive Science and Medicine Program, the Makowski Endowment Funds at the University of Colorado Anschutz Medical Campus and NIH funds (AG056046 to T R K and AG029531 to G R B and T R K). Publisher Copyright: {\textcopyright} 2019 Society for Reproduction and Fertility.",
year = "2019",
doi = "10.1530/REP-19-0392",
language = "English (US)",
volume = "158",
pages = "517--527",
journal = "Reproduction",
issn = "1470-1626",
publisher = "BioScientifica Ltd.",
number = "6",
}