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KiSS-1 Messenger Ribonucleic Acid Expression in the Hypothalamus of the Ewe Is Regulated by Sex Steroids and Season

The KiSS-1 gene encodes a family of peptides called kisspeptins, which are endogenous ligands for the G protein-coupled receptor GPR54. Kisspeptin function appears to be critical for GnRH secretion and the initiation of puberty. To test the hypothesis that steroid hormones regulate KiSS-1 mRNA expre...

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Published in:Endocrinology (Philadelphia) 2007-03, Vol.148 (3), p.1150-1157
Main Authors: Smith, Jeremy T, Clay, Colin M, Caraty, Alain, Clarke, Iain J
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Clay, Colin M
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Clarke, Iain J
description The KiSS-1 gene encodes a family of peptides called kisspeptins, which are endogenous ligands for the G protein-coupled receptor GPR54. Kisspeptin function appears to be critical for GnRH secretion and the initiation of puberty. To test the hypothesis that steroid hormones regulate KiSS-1 mRNA expression in the ewe, we examined the brains of ovary-intact (luteal phase) and ovariectomized (OVX) ewes, as well as OVX ewes that received estradiol (E) or progesterone (P) replacement. KiSS-1 mRNA-expressing cells were predominantly located in the arcuate nucleus (ARC). Here, expression was increased after OVX but returned to the level of gonad-intact animals with E treatment. Treatment with P partially restored KiSS-1 expression toward gonad-intact levels. Double-label immunohistochemistry revealed that approximately 86% of kisspeptin-immunoreactive cells in the ARC are also P-receptor positive. Finally, we tested the hypothesis that KiSS-1 mRNA is lower during anestrus, due to a non-steroid-dependent seasonal effect. In OVX ewes, expression in the ARC was lower at the time of year corresponding to anestrus. We conclude that KiSS-1 expression in the ARC of the ewe brain is negatively regulated by chronic levels of E and P, suggesting that both steroids may exert negative feedback control on GnRH secretion through altered kisspeptin signaling. Furthermore, a seasonal alteration in KiSS-1 expression in the ARC of OVX ewes strongly suggests that kisspeptin is fundamentally involved in the control of seasonal changes in reproductive function.
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Psychology</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gonadal Steroid Hormones - physiology</topic><topic>Human health and pathology</topic><topic>Hypothalamus - metabolism</topic><topic>Life Sciences</topic><topic>Ovariectomy</topic><topic>Progesterone - pharmacology</topic><topic>RNA, Messenger - metabolism</topic><topic>Seasons</topic><topic>Sheep - metabolism</topic><topic>Tissue Distribution</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Smith, Jeremy T</creatorcontrib><creatorcontrib>Clay, Colin M</creatorcontrib><creatorcontrib>Caraty, Alain</creatorcontrib><creatorcontrib>Clarke, Iain J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Smith, Jeremy T</au><au>Clay, Colin M</au><au>Caraty, Alain</au><au>Clarke, Iain J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>KiSS-1 Messenger Ribonucleic Acid Expression in the Hypothalamus of the Ewe Is Regulated by Sex Steroids and Season</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2007-03-01</date><risdate>2007</risdate><volume>148</volume><issue>3</issue><spage>1150</spage><epage>1157</epage><pages>1150-1157</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>The KiSS-1 gene encodes a family of peptides called kisspeptins, which are endogenous ligands for the G protein-coupled receptor GPR54. Kisspeptin function appears to be critical for GnRH secretion and the initiation of puberty. To test the hypothesis that steroid hormones regulate KiSS-1 mRNA expression in the ewe, we examined the brains of ovary-intact (luteal phase) and ovariectomized (OVX) ewes, as well as OVX ewes that received estradiol (E) or progesterone (P) replacement. KiSS-1 mRNA-expressing cells were predominantly located in the arcuate nucleus (ARC). Here, expression was increased after OVX but returned to the level of gonad-intact animals with E treatment. Treatment with P partially restored KiSS-1 expression toward gonad-intact levels. Double-label immunohistochemistry revealed that approximately 86% of kisspeptin-immunoreactive cells in the ARC are also P-receptor positive. Finally, we tested the hypothesis that KiSS-1 mRNA is lower during anestrus, due to a non-steroid-dependent seasonal effect. In OVX ewes, expression in the ARC was lower at the time of year corresponding to anestrus. We conclude that KiSS-1 expression in the ARC of the ewe brain is negatively regulated by chronic levels of E and P, suggesting that both steroids may exert negative feedback control on GnRH secretion through altered kisspeptin signaling. Furthermore, a seasonal alteration in KiSS-1 expression in the ARC of OVX ewes strongly suggests that kisspeptin is fundamentally involved in the control of seasonal changes in reproductive function.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>17185374</pmid><doi>10.1210/en.2006-1435</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Arcuate Nucleus of Hypothalamus - drug effects
Arcuate Nucleus of Hypothalamus - metabolism
Biological and medical sciences
Endocrinology and metabolism
Estradiol - pharmacology
Female
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation - drug effects
Gonadal Steroid Hormones - physiology
Human health and pathology
Hypothalamus - metabolism
Life Sciences
Ovariectomy
Progesterone - pharmacology
RNA, Messenger - metabolism
Seasons
Sheep - metabolism
Tissue Distribution
Tumor Suppressor Proteins - metabolism
Vertebrates: endocrinology
title KiSS-1 Messenger Ribonucleic Acid Expression in the Hypothalamus of the Ewe Is Regulated by Sex Steroids and Season
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