A novel follitropin analog inhibits follitropin activity in vitro

Naiel Azzam, Rinat Bar-Shalom, Fuad Fares

Research output: Contribution to journalArticlepeer-review


Follitropin (FSH) is a heterodimeric protein composed of an α subunit that is shared with the glycoprotein hormone family, including lutropin (LH), thyrotropin (TSH), human choriogonadotropin (hCG), and a unique β specific subunit. Both α and FSHβ subunits contain two sites of N-linked oligosaccharides, which are important for its function. FSH has a crucial function in the reproductive process in mammals. However, there are some clinical conditions, such as menopausal osteoporosis or adiposity, associated with increased FSH activity. Moreover, in some cases, carcinogenesis is evidently associated with activation of FSH receptor. Therefore, developing a follitropin antagonist might be beneficial in the treatment of these conditions. Here, we describe a novel, engineered, non-glycosylated single-chain FSH variant, prepared by site-directed mutagenesis and fusion of the coding genes of the α and β subunits. The designed variant was expressed in Chinese hamster ovary (CHO) cells and successfully secreted into the culture medium. We found that the non-glycosylated single-chain FSH analog binds with high affinity to FSH receptor and efficiently inhibits FSH activity in vitro. This variant acts at the receptor level and has the potential to serve as a follitropin antagonist for clinical applications in the future.

Original languageEnglish
Article number325
Pages (from-to)1-8
Number of pages8
Issue number3
StatePublished - 3 Mar 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Antagonist
  • FSH
  • FSH receptor
  • Glycoprotein hormones
  • N-linked oligosaccharides

ASJC Scopus subject areas

  • Pharmaceutical Science


Dive into the research topics of 'A novel follitropin analog inhibits follitropin activity in vitro'. Together they form a unique fingerprint.

Cite this