According to the Centers for Disease Control and Prevention (CDC), infertility affects about 10 percent of women in the United States ages 15-44, with issues ranging from difficulty getting pregnant to issues staying pregnant. Infertility is defined as not being able to get pregnant after one year of trying (or six months if a woman is 35 or older). The goal of this research is to investigate one important hormone in the process of reproduction, follicle-stimulating hormone (hFSH). Follicle stimulating hormone is produced by the anterior pituitary to promote gamete (egg and sperm) production (figure 1).

Figure 1. the Hypothalamic-Pituitary-Gonadal Axis

Like all hormones, hFSH depends on its receptor to function. The human follicle-stimulating hormone receptor (hFSHR) is a transmembrane receptor found in the granulosa cells of the ovary and the Sertoli cells of the testes. hFSHR is a g protein-coupled receptor (GPCR)- a transmembrane receptor that translates a signal from outside the cell to inside the cell. GPCRs and their signaling pathways are the targets of as much as 50% of all pharmaceuticals so understanding the function of hFSHR might not only be important for reproduction but might help us more broadly understand this important class of proteins.

Figure 2. Lipid raft. From Lehninger Principles of Biochemistry, 7th ed

Previous work in our lab has demonstrated that hFSHR exists in microdomains of the plasma membrane known as lipid rafts.  Lipid rafts are regions with higher concentrations of cholesterol and sphingolipids than the surrounding membrane.  They also are enriched for certain proteins such as caveolin (figure 2).

In particular, our lab is focused on 2 regions in the hFSHR sequence (figure 3)- one in the first intracellular loop (circled in black) known as the CRAC- Cholesterol Recognition/ interaction Amino Acid Motif and the other the Caveolin Binding Motif (CBM- circled in red). These regions may play a role in determining hFSHR residency in lipid raft domains in the cell membrane and therefore play a part in hFSHR function.

Figure 3. Modified from Ulloa-Aguirre A, et al Front. Endocrinol. 9:707.

We have additional projects focusing on other aspects of hFSHR receptor activity such as looking at the presence of hFSHR in osteoclasts (related to menopausal osteoporosis) as well as a broader research project using proximity labeling to find proteins in the region around hFSHR to identify possible partners that could represent future targets for understanding infertility or developing new contraceptives.