PMID- 12554748 OWN - NLM STAT- MEDLINE DCOM- 20030929 LR - 20061115 IS - 0888-8809 (Print) IS - 0888-8809 (Linking) VI - 17 IP - 2 DP - 2003 Feb TI - Estrogen receptor (ER)-beta reduces ERalpha-regulated gene transcription, supporting a "ying yang" relationship between ERalpha and ERbeta in mice. PG - 203-8 AB - Estrogen is of importance for the regulation of adult bone metabolism. The aim of the present study was to determine the role of estrogen receptor-beta (ERbeta) in vivo on global estrogen-regulated transcriptional activity in bone. The effect of estrogen in bone of ovariectomized mice was determined using microarray analysis including 9400 genes. Most of the genes (95% = 240 genes) that were increased by estrogen in wild-type (WT) mice were also increased by estrogen in ERbeta-inactivated mice. Interestingly, the average stimulatory effect of estrogen on the mRNA levels of these genes was 85% higher in ERbeta-inactivated than in WT mice, demonstrating that ERbeta reduces estrogen receptor-alpha (ERalpha)-regulated gene transcription in bone. The average stimulatory effect of estrogen on estrogen-regulated bone genes in ERalpha-inactivated mice was intermediate between that seen in WT and ERalphabeta double-inactivated mice. Thus, ERbeta inhibits ERalpha-mediated gene transcription in the presence of ERalpha, whereas, in the absence of ERalpha, it can partially replace ERalpha. In conclusion, our in vivo data indicate that an important physiological role of ERbeta is to modulate ERalpha-mediated gene transcription supporting a "Ying Yang" relationship between ERalpha and ERbeta in mice. FAU - Lindberg, Marie K AU - Lindberg MK AD - Division of Endocrinology, Department of Internal Medicine, Sahlgrenska University Hospital, S-41345 Gothenburg, Sweden. FAU - Moverare, Sofia AU - Moverare S FAU - Skrtic, Stanko AU - Skrtic S FAU - Gao, Hui AU - Gao H FAU - Dahlman-Wright, Karin AU - Dahlman-Wright K FAU - Gustafsson, Jan-Ake AU - Gustafsson JA FAU - Ohlsson, Claes AU - Ohlsson C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Endocrinol JT - Molecular endocrinology (Baltimore, Md.) JID - 8801431 RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogen Receptor beta) RN - 0 (Estrogens) RN - 0 (Receptors, Estrogen) SB - IM MH - Animals MH - Bone and Bones/drug effects/physiology MH - Estrogen Receptor alpha MH - Estrogen Receptor beta MH - Estrogens/pharmacology MH - Female MH - Gene Expression Regulation/drug effects MH - Liver/drug effects/physiology MH - Male MH - Mice MH - Mice, Mutant Strains MH - Oligonucleotide Array Sequence Analysis MH - Ovariectomy MH - Receptors, Estrogen/*genetics/*metabolism MH - Transcription, Genetic/*physiology EDAT- 2003/01/30 04:00 MHDA- 2003/09/30 05:00 CRDT- 2003/01/30 04:00 PHST- 2003/01/30 04:00 [pubmed] PHST- 2003/09/30 05:00 [medline] PHST- 2003/01/30 04:00 [entrez] AID - 10.1210/me.2002-0206 [doi] PST - ppublish SO - Mol Endocrinol. 2003 Feb;17(2):203-8. doi: 10.1210/me.2002-0206.