Grant: Project Grant

Fertility depends on the coordinated actions of many organs in the body that communicate with via hormones. The brain synthesizes and secretes gonadotropin-releasing hormone (GnRH), which controls production of two pituitary gland hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The pituitary also secretes FSH and LH into the blood in response to GnRH. FSH and LH act on the ovaries in females and the testicles in males to control the production of eggs and sperm as well as the synthesis of sex steroid hormones like estrogen and testosterone. During female reproductive cycle, there is a surge of GnRH secretion that promotes a corresponding surge of LH release, which triggers ovulation. Though we have a general understanding of where and how each of these hormones acts, fundamental gaps in knowledge remain. In this application, we propose to address three questions about the mechanisms through which GnRH acts in gonadotrope cells. First, does GnRH stimulate the production of protein called activating transcription factor 3 to selectively stimulate the synthesis of FSH? Second, does GnRH activate a novel intracellular pathway to trigger the LH surge? Finally, does GnRH stimulation of LH synthesis depend on a specific class of enzymes in the protein kinase C family? The answers to these questions will greatly advance our understanding of the hormonal control of reproduction, but may also identify potential treatments for human infertility disorders, including polycystic ovarian syndrome.