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.author Ubuka, Takayoshi en_ZA
dc.contributor.author Morgan, Kevin en_ZA
dc.contributor.author Pawson, Adam J en_ZA
dc.contributor.author Osugi, Tomohiro en_ZA
dc.contributor.author Chowdhury, Vishwajit S en_ZA
dc.contributor.author Minakata, Hiroyuki en_ZA
dc.contributor.author Tsutsui, Kazuyoshi en_ZA
dc.contributor.author Millar, Robert P en_ZA
dc.contributor.author Bentley, George E en_ZA
dc.date.accessioned 2015-11-18T07:09:52Z
dc.date.available 2015-11-18T07:09:52Z
dc.date.issued 2009 en_ZA
dc.identifier.citation Ubuka, 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.0008400 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/15135
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0008400
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This 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.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Pituitary gland en_ZA
dc.subject.other Hypothalamus en_ZA
dc.subject.other Neurons en_ZA
dc.subject.other Gonadotropins en_ZA
dc.subject.other Peptides en_ZA
dc.subject.other In situ hybridization en_ZA
dc.subject.other Polymerase chain reaction en_ZA
dc.subject.other Secretion en_ZA
dc.title Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2009 Ubuka et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Medical Biochemistry en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Ubuka, 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/11427/15135 en_ZA
dc.identifier.chicagocitation Ubuka, 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/11427/15135 en_ZA
dc.identifier.vancouvercitation Ubuka 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.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


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This 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. Except where otherwise noted, this item's license is described as This 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.