A Novel Follitropin Analog Inhibits Follitropin Activity In Vitro

Follitropin (FSH) is a heterodimeric protein composed of an alpha subunit that is shared with the glycoprotein hormone family, including lutropin (LH), thyrotropin (TSH), human choriogonadotropin (hCG), and a unique beta specific subunit. Both alpha and FSH beta 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 alpha and beta 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.

Automated summary

Follitropin (FSH) plays a crucial role in the reproductive process in mammals, but increased FSH activity is associated with clinical conditions such as menopausal osteoporosis. A non-glycosylated single-chain FSH variant has been engineered, which has the potential to act as a Follitropin antagonist by efficiently inhibiting FSH activity at the receptor level for future clinical applications.