A PROLACTIN-RELEASING PEPTIDE IN THE BRAIN

Hypothalamic peptide hormones regulate the secretion of most of the an terior pituitary hormones, that is, growth hormone, follicle-stimulati ng hormone, luteinizing hormone, thyroid-stimulating hormone and adren ocorticotropin(1,2). These peptides do not regulate the secretion of p rolactin(1,2), at least in a specific manner, however. The peptides ac t through specific receptors, which are referred to as seven-transmemb rane-domain receptors or G-protein-coupled receptors(3-7). Although pr olactin is important in pregnancy and lactation in mammals, and is inv olved in the development of the mammary glands and the promotion of mi lk synthesis(8,9), a specific prolactin-releasing hormone has remained unknown. Here we identify a potent candidate for such a hormone. We f irst proposed that there may still be unknown peptide hormone factors that control pituitary function through seven-transmembrane-domain rec eptors. We isolated the complementary DNA encoding an 'orphan' recepto r (that is, one for which the ligand is unknown). This receptor, hGR3, is specifically expressed in the human pituitary. We then searched fo r the hGR3 Ligand in the hypothalamus and identified a new peptide. wh ich shares no sequence similarity with known peptides and proteins, as an endogenous ligand. We show that this ligand is a potent prolactin- releasing factor for rat anterior pituitary cells; we have therefore n amed this peptide prolactin-releasing peptide.