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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis
PLoS ONE, Volume 4, No. 12, Article e8400, Year 2009
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Description
The existence of a hypothalamic gonadotropin-inhibiting system has been elusive. A neuropeptide named gonadotropin- inhibitory hormone (GnIH, SIKPSAYLPLRF-NH2) which directly inhibits gonadotropin synthesis and release from the pituitary was recently identified in quail hypothalamus. Here we identify GnIH homologs in the human hypothalamus and characterize their distribution and biological activity. GnIH homologs were isolated from the human hypothalamus by immunoaffinity purification, and then identified as MPHSFANLPLRF-NH2 (human RFRP-1) and VPNLPQRF-NH2 (human RFRP-3) by mass spectrometry. Immunocytochemistry revealed GnIH-immunoreactive neuronal cell bodies in the dorsomedial region of the hypothalamus with axonal projections to GnRH neurons in the preoptic area as well as to the median eminence. RT-PCR and subsequent DNA sequencing of the PCR products identified human GnIH receptor (GPR147) mRNA expression in the hypothalamus as well as in the pituitary. In situ hybridization further identified the expression of GPR147 mRNA in luteinizing hormone producing cells (gonadotropes). Human RFRP-3 has recently been shown to be a potent inhibitor of gonadotropin secretion in cultured sheep pituitary cells by inhibiting Ca2+ mobilization. It also directly modulates GnRH neuron firing. The identification of two forms of GnIH (RFRP-1 and RFRP-3) in the human hypothalamus which targets human GnRH neurons and gonadotropes and potently inhibit gonadotropin in sheep models provides a new paradigm for the regulation of hypothalamic-pituitary-gonadal axis in man and a novel means for manipulating reproductive functions. © 2009 Ubuka et al.
Authors & Co-Authors
Ubuka, Takayoshi
United States, Berkeley
University of California, Berkeley
Morgan, Kevin
United Kingdom, Edinburgh
University of Edinburgh, College of Medicine and Veterinary Medicine
Pawson, Adam J.
United Kingdom, Edinburgh
University of Edinburgh, College of Medicine and Veterinary Medicine
Osugi, Tomohiro
Japan, Tokyo
Waseda University
Chowdhury, V. S.
Japan, Tokyo
Waseda University
Minakata, Hiroyuki
Japan, Kyoto
Suntory Foundation for Life Sciences
Tsutsui, Kazuyoshi
Japan, Tokyo
Waseda University
Millar, Robert P.
United Kingdom, Edinburgh
University of Edinburgh, College of Medicine and Veterinary Medicine
South Africa, Cape Town
University of Cape Town
Bentley, George E.
United States, Berkeley
University of California, Berkeley
Statistics
Citations: 9
Authors: 9
Affiliations: 5
Identifiers
Doi:
10.1371/journal.pone.0008400
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Sexual And Reproductive Health