Investigating the Role of Caveolin in Human FSH Receptor Activity

It is estimated that approximately 10-15% of couples in the United States struggle with infertility, meaning that they have trouble getting or staying pregnant. Within these cases approximately one third are the result of male fertility problems with another third being the result of female fertility problems with the final third being a combination of male and female fertility problems. Treatment for infertility can consist of a combination of medications, surgical interventions and assisted reproductive technologies such as in vitro fertilization (IVF). IVF normally includes the use of human follicle stimulating hormone (hFSH), a gonadotropic hormone that is produced in the anterior pituitary gland that is involved in fertility in both males and females. Further understanding of hFSH, its receptor and its signaling pathway could provide alternate treatments for infertility. The hFSH receptor (hFSHR) is a g protein-coupled receptor (GPCR). Previous research in our lab has shown that the hFSHR localizes in lipid rafts which are specialized sections of the plasma membrane enriched with sphingolipids and cholesterol, making them more rigid compared with other sections of the plasma membrane. The structural protein caveolin is also thought to play a role in the localization and removal of GPCRs from lipid rafts which has implications for the regulation of hFSHR activity. In this study, human embryonic kidney cells cells expressing hFSHR were transfected with a dominant negative (S80E) caveolin mutant to investigate the role of caveolin in the hFSHR activity. We found that disrupting the function of caveolin resulted in decreased signaling via the p44/42 and CREB pathways. Further understanding of hFSH and its receptor’s activity can help provide alternative infertility treatments that are more effective for both male and female infertility.