Gonadotrophin-releasing hormone--diversity of functions and clinical applications

Gonadotrophin-releasing hormone (GnRH) plays a pivotal role in the regulation of the reproductive system. Chemically synthesised GnRH and analogues have found wide application in clinical medicine. Pulsatile administration of GnRH is used in the treatment of infertility and cryptorchidism. GnRH agonists inhibit gonadotrophin by pituitary desensitisation while antagonists compete out the effects of endogenous GnRH. These agents find application in contraception, the treatment of hormone-dependent neoplasms, precocious puberty, endometriosis, porphyria and disturbances of the menstrual cycle. It is now apparent that GnRH has been co-opted during evolution for functions other than the stimulation of gonadotrophins. GnRH has paracrine (local) effects in the gonads and placenta, acts as a neurotransmitter in the central nervous system, and has autocrine regulatory effects in some tumour cells. Evolutionary studies in non-mammalian vertebrates show that the GnRH gene has been duplicated to produce different molecular forms of unknown function. In addition to producing GnRH, the GnRH precursor is cleaved to produce peptides with novel activities, including prolactin inhibition.