Estradiol Down-Regulates RF-Amide-Related Peptide (RFRP) Expression in the Mouse Hypothalamus

Estradiol down-regulates preproRFRP mRNA expression and a subset of RFRP neurons contains low levels of nuclear estrogen receptor α in mice. In most mammals, RF-amide-related peptides are synthesized in the dorsomedial hypothalamic nucleus and regulate reproduction via inhibiting GnRH neurons and, p...

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Veröffentlicht in:Endocrinology (Philadelphia) 2011-04, Vol.152 (4), p.1684-1690
Hauptverfasser: Molnár, C. S, Kalló, I, Liposits, Z, Hrabovszky, E
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creator Molnár, C. S
Kalló, I
Liposits, Z
Hrabovszky, E
description Estradiol down-regulates preproRFRP mRNA expression and a subset of RFRP neurons contains low levels of nuclear estrogen receptor α in mice. In most mammals, RF-amide-related peptides are synthesized in the dorsomedial hypothalamic nucleus and regulate reproduction via inhibiting GnRH neurons and, possibly, adenohypophyseal gonadotrophs. In the present study, we investigated the possibility that RFRP-synthesizing neurons are involved in estrogen feedback signaling to the reproductive axis in mice. First, we used quantitative in situ hybridization and compared the expression of prepro-RFRP mRNA of ovariectomized mice, with and without 17β-estradiol (E2) replacement. Subcutaneous administration of E2 via silastic capsules for 4 d significantly down-regulated prepro-RFRP mRNA expression. The underlying receptor mechanism was investigated with immunohistochemistry. In ovariectomized mice, low levels of nuclear estrogen receptor (ER)-α immunoreactivity were detectable in 18.7 ± 3.8% of RFRP neurons. The majority of RFRP neurons showed no ER-α signal, and RFRP neurons did not exhibit ER-β immunoreactivity. Results of these studies indicate that RFRP is a negatively estradiol-regulated neurotransmitter/neuromodulator in mice. The estrogenic down-regulation of RFRP expression may contribute to estrogen feedback to the reproductive axis. The issue of whether E2 regulates RFRP neurons directly or indirectly remains open given that ER-α immunoreactivity is present only at low levels in a subset of these cells.
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The underlying receptor mechanism was investigated with immunohistochemistry. In ovariectomized mice, low levels of nuclear estrogen receptor (ER)-α immunoreactivity were detectable in 18.7 ± 3.8% of RFRP neurons. The majority of RFRP neurons showed no ER-α signal, and RFRP neurons did not exhibit ER-β immunoreactivity. Results of these studies indicate that RFRP is a negatively estradiol-regulated neurotransmitter/neuromodulator in mice. The estrogenic down-regulation of RFRP expression may contribute to estrogen feedback to the reproductive axis. 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Psychology ; Gene expression ; Gonadotropin-releasing hormone ; Hybridization ; Hypothalamus ; Hypothalamus - drug effects ; Hypothalamus - metabolism ; Immunohistochemistry ; In Situ Hybridization ; Mice ; Neuromodulation ; Neurons ; Neuropeptides - genetics ; Neuropeptides - metabolism ; Ovariectomy ; Peptides ; Pituitary (anterior) ; Radio frequency ; Receptors ; RNA, Messenger - genetics ; Sex hormones ; Synthesis ; Vertebrates: endocrinology ; Xenoestrogens</subject><ispartof>Endocrinology (Philadelphia), 2011-04, Vol.152 (4), p.1684-1690</ispartof><rights>Copyright © 2011 by The Endocrine Society</rights><rights>Copyright © 2011 by The Endocrine Society 2011</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-3f3f25aaa52576cd27d392fef68e43b7d4ab44d88fc1418c4a71ce96d4f102f63</citedby><cites>FETCH-LOGICAL-c528t-3f3f25aaa52576cd27d392fef68e43b7d4ab44d88fc1418c4a71ce96d4f102f63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=24070290$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21325049$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Molnár, C. S</creatorcontrib><creatorcontrib>Kalló, I</creatorcontrib><creatorcontrib>Liposits, Z</creatorcontrib><creatorcontrib>Hrabovszky, E</creatorcontrib><title>Estradiol Down-Regulates RF-Amide-Related Peptide (RFRP) Expression in the Mouse Hypothalamus</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Estradiol down-regulates preproRFRP mRNA expression and a subset of RFRP neurons contains low levels of nuclear estrogen receptor α in mice. In most mammals, RF-amide-related peptides are synthesized in the dorsomedial hypothalamic nucleus and regulate reproduction via inhibiting GnRH neurons and, possibly, adenohypophyseal gonadotrophs. In the present study, we investigated the possibility that RFRP-synthesizing neurons are involved in estrogen feedback signaling to the reproductive axis in mice. 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Psychology</subject><subject>Gene expression</subject><subject>Gonadotropin-releasing hormone</subject><subject>Hybridization</subject><subject>Hypothalamus</subject><subject>Hypothalamus - drug effects</subject><subject>Hypothalamus - metabolism</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization</subject><subject>Mice</subject><subject>Neuromodulation</subject><subject>Neurons</subject><subject>Neuropeptides - genetics</subject><subject>Neuropeptides - metabolism</subject><subject>Ovariectomy</subject><subject>Peptides</subject><subject>Pituitary (anterior)</subject><subject>Radio frequency</subject><subject>Receptors</subject><subject>RNA, Messenger - genetics</subject><subject>Sex hormones</subject><subject>Synthesis</subject><subject>Vertebrates: endocrinology</subject><subject>Xenoestrogens</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kd9r1TAUx4Mo7jp981kCIptgZ361aR_HvHcTJo6LPkrITU5cR5vUpGXuvzfdrQ5En8I5fDjfH0HoJSUnlFHyHvwJI5QUVND6EVrRRpSFpJI8RitCKC8kY_IAPUvpJo9CCP4UHTDKWUlEs0Lf1mmM2rahwx_CrS-28H3q9AgJbzfFad9ayKt5YfEVDGOe8fF2s716i9c_hwgptcHj1uPxGvCnMCXAF3dDGK91p_spPUdPnO4SvFjeQ_R1s_5ydlFcfj7_eHZ6WZiS1WPBHXes1FqXrJSVsUxa3jAHrqpB8J20Qu-EsHXtzJzSCC2pgaaywlHCXMUP0dH-7hDDjwnSqPo2Geg67SGbUnVZy5oLyTP5-i_yJkzRZ3OKU04qKquGZOrdnjIxpBTBqSG2vY53ihI1t67Aq7l1NfvJ-Kvl6LTrwf6Bf9ecgTcLoJPRnYvamzY9cIJIwu51lxxhGv4nWSySfE-Ct8HE1sP9bzyk-afRXzUlpUk</recordid><startdate>20110401</startdate><enddate>20110401</enddate><creator>Molnár, C. 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S</au><au>Kalló, I</au><au>Liposits, Z</au><au>Hrabovszky, E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Estradiol Down-Regulates RF-Amide-Related Peptide (RFRP) Expression in the Mouse Hypothalamus</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2011-04-01</date><risdate>2011</risdate><volume>152</volume><issue>4</issue><spage>1684</spage><epage>1690</epage><pages>1684-1690</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>Estradiol down-regulates preproRFRP mRNA expression and a subset of RFRP neurons contains low levels of nuclear estrogen receptor α in mice. In most mammals, RF-amide-related peptides are synthesized in the dorsomedial hypothalamic nucleus and regulate reproduction via inhibiting GnRH neurons and, possibly, adenohypophyseal gonadotrophs. 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The estrogenic down-regulation of RFRP expression may contribute to estrogen feedback to the reproductive axis. The issue of whether E2 regulates RFRP neurons directly or indirectly remains open given that ER-α immunoreactivity is present only at low levels in a subset of these cells.</abstract><cop>Chevy Chase, MD</cop><pub>Endocrine Society</pub><pmid>21325049</pmid><doi>10.1210/en.2010-1418</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Journals@Ovid Complete
subjects 17β-Estradiol
Animals
Biological and medical sciences
Down-regulation
Estradiol - pharmacology
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Estrogen Receptor beta - genetics
Estrogen Receptor beta - metabolism
Estrogen receptors
Estrogens
Feedback
Fundamental and applied biological sciences. Psychology
Gene expression
Gonadotropin-releasing hormone
Hybridization
Hypothalamus
Hypothalamus - drug effects
Hypothalamus - metabolism
Immunohistochemistry
In Situ Hybridization
Mice
Neuromodulation
Neurons
Neuropeptides - genetics
Neuropeptides - metabolism
Ovariectomy
Peptides
Pituitary (anterior)
Radio frequency
Receptors
RNA, Messenger - genetics
Sex hormones
Synthesis
Vertebrates: endocrinology
Xenoestrogens
title Estradiol Down-Regulates RF-Amide-Related Peptide (RFRP) Expression in the Mouse Hypothalamus
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