Bioactivity of recombinant hFSH glycosylation variants in primary cultures of porcine granulosa cells

Aixin Liang, Michele R. Plewes, Guohua Hua, Xiaoying Hou, Haley R. Blum, Emilia Przygrodzka, Jitu W. George, Kendra L. Clark, George R. Bousfield, Viktor Y. Butnev, Jeffrey V. May, John S. Davis

Research output: Contribution to journalArticle

Abstract

Previous studies have reported hypo-glycosylated FSH and fully-glycosylated FSH to be naturally occurring in humans, and these glycoforms exist in changing ratios over a woman's lifespan. The precise cellular and molecular effects of recombinant human FSH (hFSH) glycoforms, FSH21 and FSH24, have not been documented in primary granulosa cells. Herein, biological responses to FSH21 and FSH24 were compared in primary porcine granulosa cells. Hypo-glycosylated hFSH21 was significantly more effective than fully-glycosylated hFSH24 at stimulating cAMP accumulation and protein kinase A (PKA) activity, leading to the higher phosphorylation of CREB and β-Catenin. Compared to fully-glycosylated hFSH24, hypo-glycosylated hFSH21 also induced greater levels of transcripts for HSD3B, STAR and INHA, and higher progesterone production. Our results demonstrate that hypo-glycosylated hFSH21 exerts more robust activation of intracellular signals associated with steroidogenesis than fully-glycosylated hFSH24 in primary porcine granulosa cells, and furthers our understanding of the differing bioactivities of FSH glycoforms in the ovary.

Original languageEnglish (US)
Article number110911
JournalMolecular and Cellular Endocrinology
Volume514
DOIs
StatePublished - Aug 20 2020

Keywords

  • Cell signaling
  • Follicle
  • Ovary
  • Protein kinase A
  • Steroidogenesis
  • β-Catenin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Fingerprint Dive into the research topics of 'Bioactivity of recombinant hFSH glycosylation variants in primary cultures of porcine granulosa cells'. Together they form a unique fingerprint.

  • Cite this

    Liang, A., Plewes, M. R., Hua, G., Hou, X., Blum, H. R., Przygrodzka, E., George, J. W., Clark, K. L., Bousfield, G. R., Butnev, V. Y., May, J. V., & Davis, J. S. (2020). Bioactivity of recombinant hFSH glycosylation variants in primary cultures of porcine granulosa cells. Molecular and Cellular Endocrinology, 514, [110911]. https://doi.org/10.1016/j.mce.2020.110911