Stacy Hu L&S Sciences
Understanding Circadian Control of the Luteinizing Hormone Surge with Inhibitory DREADDs
All steps of female reproduction—including ovulation, fertilization, and pregnancy—rely on timed secretion of reproductive hormones, which are synchronized to external time by exposure to sunlight during daytime and darkness at night. Circadian disruption (ex. irregular work/sleep schedules) can lead to reproductive issues; thus, understanding how the circadian system controls reproductive hormones is critical for identifying potential therapeutic targets for treating infertility and other gynecological disorders, and could help develop safer and more effective contraceptives. The “master clock” of the body’s circadian system is the brain’s suprachiasmatic nucleus (SCN), which releases a variety of neurochemicals (e.g., VIP, AVP) to coordinate a surge in luteinizing hormone (LH) which triggers ovulation. Two neuronal cell types that mediate this pathway are kisspeptin and gonadotropin-inhibitory hormone (GnIH). To examine the role of AVP and VIP neurons in coordinating the LH surge necessary for ovulation, I will inhibit their communication to kisspeptin and GnIH cells using hMR4D(Gi), a Designer Receptors Exclusively Activated by Designer Drug (DREADD) that inhibits neurotransmitter release when activated by the synthetic compound CNO.