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A prolactin-releasing peptide in the brain

Nature volume 393, pages 272–276 (1998)Cite this article

An Addendum to this article was published on 16 July 1998

Abstract

Hypothalamic peptide hormones regulate the secretion of most ofthe anterior pituitary hormones, that is, growth hormone, follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone and adrenocorticotropin1,2. These peptides do not regulate the secretion of prolactin1,2, 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 receptors3,4,5,6,7. 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 synthesis8,9, 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.

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Figure 1: Purification of peptide ligands for hGR3 from bovine hypothalamic extract.
Figure 2: Amino-acid sequences of bovine, rat and human preproproteins containing PrRP.
Figure 3: Specific interaction of synthetic PrRPs with hGR3 and UHR-1.
Figure 4: Promotion of PRL secretion from rat anterior pituitary cells by PrRP.
Figure 5: Relation between arachidonic acid metabolism and PRL secretion induced by PrRP in primary cultured rat anterior pituitary cells.

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Acknowledgements

We thank H. Okazaki and K. Tsukamoto for discussions throughout this study, and Y. Ishibashi, J. Noguchi, Y. Matsumoto, T. Moriya and M. Suenaga for collaboration.

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Authors and Affiliations

  1. Pharmaceutical Discovery Research Division, Discovery Research Laboratories I, 10 Wadai, Tsukuba, 300-4293, Ibaraki, Japan

    Shuji Hinuma, Yugo Habata, Ryo Fujii, Yuji Kawamata, Masaki Hosoya, Shoji Fukusumi, Chieko Kitada, Yoshinori Masuo, Hirokazu Matsumoto, Tsutomu Kurokawa, Haruo Onda & Masahiko Fujino

  2. Pharmaceutical Research Division, 10 Wadai, Tsukuba, 300-4293, Ibaraki, Japan

    Tsuneo Asano & Osamu Nishimura

  3. Pharmaceutical Development Division, Takeda Chemical Industries Ltd, 10 Wadai, Tsukuba, 300-4293, Ibaraki, Japan

    Masahiro Sekiguchi

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Correspondence to Shuji Hinuma.

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Hinuma, S., Habata, Y., Fujii, R. et al. A prolactin-releasing peptide in the brain. Nature 393, 272–276 (1998). https://doi.org/10.1038/30515

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