Visualization of the Interactions between the Human Follicle Stimulating Hormone Receptor and Lipid Rafts

Unintended pregnancy is an experience shared across the globe. There were roughly 121 million unintended pregnancies per year worldwide between 2015 and 2019. According to estimates, about 61% of these pregnancies ended in abortion. With access to safe and legal abortions varying across countries around the world, access to preventative measures, such as effective contraception, is more important than ever. One of the most common forms of birth control are oral contraceptives which rely on progesterone and in some cases estrogen to regulate a woman's sexual reproduction. However, not all women are able to take these hormones, causing there to be a need for alternate methods of female contraception. The human follicle stimulating hormone (hFSH) is a gonadotropin and is one of the main hormones that regulates sexual reproduction in both males and females. This hormone is produced by the anterior pituitary and binds to receptors (hFSHR) in the ovaries or the testes, promoting either oogenesis in females or spermatogenesis in males. FSHR is a G protein-coupled receptor (GPCR) and is found on the membrane of target cells. Previous work in our lab has shown that FSHR lies within lipid raft domains on the plasma membrane. Lipid rafts have high levels of cholesterol and sphingolipids, giving them a thicker, rigid structure in comparison to other areas of the membrane. Preliminary data has shown that FSHR residency in the lipid raft is necessary for signal transduction and that disruption of lipid rafts leads to interference in the response to FSH. The goal of this research was to demonstrate residency of hFSHR in lipid rafts using a multipronged approach including sucrose gradients and confocal microscopy. hFSHR was identified on the membrane using a monoclonal antibody and lipid rafts were labeled by identifying ganglioside rich regions on the membrane. When cells were treated with FSH, hFSHR colocalization with lipid rafts was decreased. The results from this research will help us better understand the human reproductive pathway, allowing for the development of more effective and available contraceptives for both men and women.