Gonadotropin-releasing hormone (GnRH) is released in a pulsatile manner that varies with the reproductive cycle. This hypothalamic hormone is transported to the pituitary, where it binds to specific receptors and regulates the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Localized to the cell membrane, GnRHR2 mediates its own receptor activity via association with G proteins, thereby activating a phosphatidylinositol-calcium second messenger system that regulates GnRHR2 function. GnRHR2 is thought to have potent antiproliferative effects on ovarian and endometrial cancer cells, suggesting a possible role in tumor suppression. Due to alternative splicing events, GnRHR2 is expressed as two isoforms.