Improving Contraception and Fertility Treatments Through Identification of Proteins Proximal to the human FSH Receptor

Follicle Stimulating Hormone, or FSH, is a critical hormone involved in reproduction. In men, FSH signaling in Sertoli cells triggers spermatogenesis, and in women, FSH signaling in the granulosa cells is responsible for follicular development. Current hormonal contraceptives have been found to have incredibly high effectiveness but can also carry multiple side effects. In addition, their effectiveness can be altered due to an individual’s FSH, estrogen, progesterone , or GnRH levels. All FSH signaling happens through the FSH receptor, a member of the G-protein Coupled Receptor (GPCR) family. This receptor is known to interact with many other proteins along its complicated signaling pathway, and there are still many more associated proteins yet to be discovered. Using the APEX technique, the proteins proximal to the FSH receptor were labelled and purified. In the future, these proteins could be analyzed using HPLC-MS, and identified using various computer software. Small proximal proteins, like those isolated in this study, have been shown to allow for receptor activation and function modulation. Thus, this study opens the doors for much more work in the field of contraceptives for both men and women. Another potential benefit from identifying FSHR associated proteins would be in developing new approaches for In Vitro Fertilization (IVF). To perform IVF, FSH is given to women to cause rapid follicle stimulation and maturation. This produces multiple ovulation events and allows for a higher chance of pregnancy. The problem, however, is that FSH alone is expensive, and the chance of multiple pregnancies is vastly increased. Targeting the pathways downstream of the FSH receptor could allow for more careful modulation of the follicle growth and could be much less expensive, vastly lowering the cost of IVF and making it a more viable option for those seeking infertility treatment.