A prolactin-releasing peptide in the brain

Abstract

Hypothalamic peptide hormones regulate the secretion of most of the anterior pituitary hormones, that is, growth hormone, follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone and adrenocorticotropin. These peptides do not regulate the secretion of prolactin, at least in a specific manner, however. The peptides act through specific receptors, which are referred to as seven-transmembrane-domain receptors or G-protein-coupled receptors. Although prolactin is important in pregnancy and lactation in mammals, and is involved in the development of the mammary glands and the promotion of milk synthesis, a specific prolactin-releasing hormone has remained unknown. Here we identify a potent candidate for such a hormone. We first proposed that there may still be unknown peptide hormone factors that control pituitary function through seven-transmembrane-domain receptors. We isolated the complementary DNA encoding an 'orphan' receptor (that is, one for which the ligand is unknown). This receptor, hGR3, is specifically expressed in the human pituitary. We then searched for the hGR3 ligand in the hypothalamus and identified a new peptide, which 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 named this peptide prolactin-releasing peptide.

Effects of the dopamine agonist cabergoline on the pulsatile and TRH-induced secretion of prolactin, LH, and testosterone in male beagle dogs

“…Only a few years ago, a specific prolactin-release promoting peptide has been identified and characterised in the hypothalamus [11,12]. In addition, several other prolactin-stimulating factors have been reported, such as serotonin [13] and thyrotrophin-releasing hormone (TRH) [14][15][16][17][18].…”

Orphan G-protein-coupled Receptors

“…A similar approach was utilized to discover the orexin peptides (Saihrai et al, 1998). and the prolactin releasing peptide (Hinuma et al, 1998). which has been shown to be the endogenous ligand for an orphan receptor, GPRIO, discovered first by our labomtory (Marchese et al.…”

“…GPRlO was of interest to many researches, especially because of its expression in the hypothalamus (see below), suggesting a role for this receptor in some neuroendocrine function, which spurred a search to discover the endogenous ligand, in efforts to elucidate its precise physiological role. Recently, a novel peptide was isolated from rat hypothalamus by using a GPRlOas the target in agonist activation assays, and is apparently the cognate ligand for the receptor encoded by GPRlO (Hinuma et al, 1998). The novel peptide has been called prolactin releasing peptide, because of its ability to cause release of prolactin from the pituitary (Hinuma et al, 1998).…”

“…Recently, a novel peptide was isolated from rat hypothalamus by using a GPRlOas the target in agonist activation assays, and is apparently the cognate ligand for the receptor encoded by GPRlO (Hinuma et al, 1998). The novel peptide has been called prolactin releasing peptide, because of its ability to cause release of prolactin from the pituitary (Hinuma et al, 1998).…”

“…In efforts to identify the endogenous ligand for this receptor, a cell line stably expressing this orphan receptor was tested in agonist response assays to biological extracts from hypothalamus (Hinuma et al, 1998). After several fractionation steps the active components, two overlapping peptides of 30 and 20 amino acids in length, were isolated which caused the release of arachidonic acid (Hinuma el al., 1998).…”