PMID- 26726951 OWN - NLM STAT- MEDLINE DCOM- 20161031 LR - 20191126 IS - 1944-9917 (Electronic) IS - 0888-8809 (Print) IS - 0888-8809 (Linking) VI - 30 IP - 2 DP - 2016 Feb TI - Divergent Regulation of ER and Kiss Genes by 17beta-Estradiol in Hypothalamic ARC Versus AVPV Models. PG - 217-33 LID - 10.1210/me.2015-1189 [doi] AB - Kisspeptin (Kiss) and G-protein-coupled receptor (Gpr)54 have emerged as key regulators of reproduction. 17beta-estradiol (E2)-mediated regulation of these neurons is nuclei specific, where anteroventral periventricular (AVPV) Kiss neurons are positively regulated by E2, whereas arcuate nucleus (ARC) neurons are inhibited. We have generated immortalized Kiss cell lines from male and female adult-derived murine hypothalamic primary culture, as well as cell lines from microdissected AVPV and ARC from female Kiss-green fluorescent protein (GFP) mice. All exhibit endogenous Kiss-1 expression, estrogen receptors (ER)s (ERalpha, ERbeta, and Gpr30), as well as known markers of AVPV Kiss neurons in the mHypoA-50 and mHypoA-Kiss/GFP-4, vs markers of ARC Kiss neurons in the mHypoA-55 and the mHypoA-Kiss/GFP-3 lines. There was an increase in Kiss-1 mRNA expression at 24 hours in the AVPV lines and a repression of Kiss-1 mRNA at 4 hours in the ARC lines. An E2-mediated decrease in ERalpha mRNA expression at 24 hours in the AVPV cell lines was detected, and a significant decrease in Gpr30, ERalpha, and ERbeta mRNA levels at 4 hours in the ARC cell lines was evident. ER agonists and antagonists determined the specific ERs responsible for mediating changes in gene expression. In the AVPV, ERalpha is required but not ERbeta or GPR30, vs the ARC Kiss-expressing cell lines that require GPR30, and either ERalpha and/or ERbeta. We determined cAMP response element-binding protein 1 was necessary for the down-regulation of Kiss-1 mRNA expression using small interfering RNA knockdown in the ARC cell model. These studies elucidate some of the molecular events involved in the differential E2-mediated regulation of unique and specific Kiss neuronal models. FAU - Treen, Alice K AU - Treen AK AD - Departments of Physiology (A.K.T., V.L., J.A.C., P.S.D., D.T., W.Y., G.L.K., Z.F., D.D.B.), Medicine (D.D.B.), and Obstetrics and Gynaecology (D.D.B.), University of Toronto, and Division of Cellular and Molecular Biology (D.D.B.), Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada M5S 1A8. FAU - Luo, Vicky AU - Luo V AD - Departments of Physiology (A.K.T., V.L., J.A.C., P.S.D., D.T., W.Y., G.L.K., Z.F., D.D.B.), Medicine (D.D.B.), and Obstetrics and Gynaecology (D.D.B.), University of Toronto, and Division of Cellular and Molecular Biology (D.D.B.), Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada M5S 1A8. FAU - Chalmers, Jennifer A AU - Chalmers JA AD - Departments of Physiology (A.K.T., V.L., J.A.C., P.S.D., D.T., W.Y., G.L.K., Z.F., D.D.B.), Medicine (D.D.B.), and Obstetrics and Gynaecology (D.D.B.), University of Toronto, and Division of Cellular and Molecular Biology (D.D.B.), Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada M5S 1A8. FAU - Dalvi, Prasad S AU - Dalvi PS AD - Departments of Physiology (A.K.T., V.L., J.A.C., P.S.D., D.T., W.Y., G.L.K., Z.F., D.D.B.), Medicine (D.D.B.), and Obstetrics and Gynaecology (D.D.B.), University of Toronto, and Division of Cellular and Molecular Biology (D.D.B.), Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada M5S 1A8. FAU - Tran, Dean AU - Tran D AD - Departments of Physiology (A.K.T., V.L., J.A.C., P.S.D., D.T., W.Y., G.L.K., Z.F., D.D.B.), Medicine (D.D.B.), and Obstetrics and Gynaecology (D.D.B.), University of Toronto, and Division of Cellular and Molecular Biology (D.D.B.), Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada M5S 1A8. FAU - Ye, Wenqing AU - Ye W AD - Departments of Physiology (A.K.T., V.L., J.A.C., P.S.D., D.T., W.Y., G.L.K., Z.F., D.D.B.), Medicine (D.D.B.), and Obstetrics and Gynaecology (D.D.B.), University of Toronto, and Division of Cellular and Molecular Biology (D.D.B.), Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada M5S 1A8. FAU - Kim, Ginah L AU - Kim GL AD - Departments of Physiology (A.K.T., V.L., J.A.C., P.S.D., D.T., W.Y., G.L.K., Z.F., D.D.B.), Medicine (D.D.B.), and Obstetrics and Gynaecology (D.D.B.), University of Toronto, and Division of Cellular and Molecular Biology (D.D.B.), Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada M5S 1A8. FAU - Friedman, Zoey AU - Friedman Z AD - Departments of Physiology (A.K.T., V.L., J.A.C., P.S.D., D.T., W.Y., G.L.K., Z.F., D.D.B.), Medicine (D.D.B.), and Obstetrics and Gynaecology (D.D.B.), University of Toronto, and Division of Cellular and Molecular Biology (D.D.B.), Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada M5S 1A8. FAU - Belsham, Denise D AU - Belsham DD AD - Departments of Physiology (A.K.T., V.L., J.A.C., P.S.D., D.T., W.Y., G.L.K., Z.F., D.D.B.), Medicine (D.D.B.), and Obstetrics and Gynaecology (D.D.B.), University of Toronto, and Division of Cellular and Molecular Biology (D.D.B.), Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada M5S 1A8. LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160104 PL - United States TA - Mol Endocrinol JT - Molecular endocrinology (Baltimore, Md.) JID - 8801431 RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (GPER1 protein, mouse) RN - 0 (Kisspeptins) RN - 0 (Peptides) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (Transcription Factor AP-1) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 4TI98Z838E (Estradiol) SB - IM MH - Animals MH - Arcuate Nucleus of Hypothalamus/drug effects/*metabolism MH - Binding Sites MH - Cell Line MH - Cell Membrane/drug effects/metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Estradiol/*pharmacology MH - Female MH - Gene Expression Profiling MH - Gene Expression Regulation/*drug effects MH - Gene Knockdown Techniques MH - Green Fluorescent Proteins/metabolism MH - Hypothalamus, Anterior/drug effects/*metabolism MH - Kisspeptins/*genetics/metabolism MH - Male MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Models, Biological MH - Neurons/drug effects/metabolism MH - Peptides/metabolism MH - Promoter Regions, Genetic/genetics MH - RNA, Messenger/genetics/metabolism MH - Receptors, Estrogen/genetics/*metabolism MH - Receptors, G-Protein-Coupled/genetics/metabolism MH - Sex Characteristics MH - Transcription Factor AP-1/metabolism PMC - PMC5414652 EDAT- 2016/01/05 06:00 MHDA- 2016/11/01 06:00 PMCR- 2017/02/01 CRDT- 2016/01/05 06:00 PHST- 2016/01/05 06:00 [entrez] PHST- 2016/01/05 06:00 [pubmed] PHST- 2016/11/01 06:00 [medline] PHST- 2017/02/01 00:00 [pmc-release] AID - ME-15-1189 [pii] AID - 10.1210/me.2015-1189 [doi] PST - ppublish SO - Mol Endocrinol. 2016 Feb;30(2):217-33. doi: 10.1210/me.2015-1189. Epub 2016 Jan 4.