GnRH receptor signalling
Ursula B. Kaiser
The hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH), is the key neuroendocrine regulator of mammalian reproductive development and function. GnRH binds to its target, the GnRH receptor (GnRHR), on pituitary gonadotropes to stimulate the synthesis and intermittent release of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn stimulate gametogenesis and gonadal hormone synthesis. Thus GnRH, via the GnRHR, plays a pivotal role in the coordination of reproductive events, and dysregulation of GnRH signaling underlies many reproductive disorders, such as polycystic ovarian syndrome (PCOS), hypothalamic amenorrhea, disorders of pubertal maturation, and infertility. GnRH is released in a pulsatile manner, with the frequency and amplitude of GnRH pulses varying temporally and developmentally, for example during different phases of the menstrual or estrous cycle. These patterns of pulsatile GnRH release activate distinct signal transduction cascades to contribute to frequency decoding of GnRH pulsatility by gonaodtropes, resulting in differential LH and FSH synthesis and secretion. The identification and studies of mutations in the GnRHR in patients with disorders of reproductive maturation and function have further highlighted the importance of GnRHR signalling in regulation of gonadotropin synthesis and secretion.