Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis

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dc.contributor.authorUbuka, Takayoshien_ZA
dc.contributor.authorMorgan, Kevinen_ZA
dc.contributor.authorPawson, Adam Jen_ZA
dc.contributor.authorOsugi, Tomohiroen_ZA
dc.contributor.authorChowdhury, Vishwajit Sen_ZA
dc.contributor.authorMinakata, Hiroyukien_ZA
dc.contributor.authorTsutsui, Kazuyoshien_ZA
dc.contributor.authorMillar, Robert Pen_ZA
dc.contributor.authorBentley, George Een_ZA
dc.date.accessioned2015-11-18T07:09:52Z
dc.date.available2015-11-18T07:09:52Z
dc.date.issued2009en_ZA
dc.description.abstractThe existence of a hypothalamic gonadotropin-inhibiting system has been elusive. A neuropeptide named gonadotropin-inhibitory hormone (GnIH, SIKPSAYLPLRF-NH 2 ) 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-NH 2 (human RFRP-1) and VPNLPQRF-NH 2 (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 Ca 2+ 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.en_ZA
dc.identifier.apacitationUbuka, T., Morgan, K., Pawson, A. J., Osugi, T., Chowdhury, V. S., Minakata, H., ... Bentley, G. E. (2009). Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis. <i>PLoS One</i>, http://hdl.handle.net/11427/15135en_ZA
dc.identifier.chicagocitationUbuka, Takayoshi, Kevin Morgan, Adam J Pawson, Tomohiro Osugi, Vishwajit S Chowdhury, Hiroyuki Minakata, Kazuyoshi Tsutsui, Robert P Millar, and George E Bentley "Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis." <i>PLoS One</i> (2009) http://hdl.handle.net/11427/15135en_ZA
dc.identifier.citationUbuka, T., Morgan, K., Pawson, A. J., Osugi, T., Chowdhury, V. S., Minakata, H., ... & Bentley, G. E. (2009). Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis. PLoS One, 4(12), e8400. doi:10.1371/journal.pone.0008400en_ZA
dc.identifier.ris TY - Journal Article AU - Ubuka, Takayoshi AU - Morgan, Kevin AU - Pawson, Adam J AU - Osugi, Tomohiro AU - Chowdhury, Vishwajit S AU - Minakata, Hiroyuki AU - Tsutsui, Kazuyoshi AU - Millar, Robert P AU - Bentley, George E AB - The existence of a hypothalamic gonadotropin-inhibiting system has been elusive. A neuropeptide named gonadotropin-inhibitory hormone (GnIH, SIKPSAYLPLRF-NH 2 ) 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-NH 2 (human RFRP-1) and VPNLPQRF-NH 2 (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 Ca 2+ 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. DA - 2009 DB - OpenUCT DO - 10.1371/journal.pone.0008400 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis TI - Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis UR - http://hdl.handle.net/11427/15135 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15135
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0008400
dc.identifier.vancouvercitationUbuka T, Morgan K, Pawson AJ, Osugi T, Chowdhury VS, Minakata H, et al. Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis. PLoS One. 2009; http://hdl.handle.net/11427/15135.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Medical Biochemistryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2009 Ubuka et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherPituitary glanden_ZA
dc.subject.otherHypothalamusen_ZA
dc.subject.otherNeuronsen_ZA
dc.subject.otherGonadotropinsen_ZA
dc.subject.otherPeptidesen_ZA
dc.subject.otherIn situ hybridizationen_ZA
dc.subject.otherPolymerase chain reactionen_ZA
dc.subject.otherSecretionen_ZA
dc.titleIdentification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axisen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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