PMID- 7935425 OWN - NLM STAT- MEDLINE DCOM- 19941118 LR - 20210526 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 14 IP - 11 DP - 1994 Nov TI - Endogenous retinoid X receptors can function as hormone receptors in pituitary cells. PG - 7105-10 AB - Retinoids regulate gene transcription by interacting with both retinoic acid (RA) receptors (RARs) and retinoid X receptors (RXRs). Since unliganded RXRs can act as heterodimerization partners for RARs and other nuclear hormone receptors, it is unclear whether ligand binding by RXRs actually regulates the expression of naturally occurring genes. To address this issue, we synthesized the RXR-selective retinoid SR11237 and confirmed its specificity in transient transfection and proteolytic susceptibility assays before using it to assess the contribution of ligand-activated RXRs to retinoid action. Unlike RAR ligands, SR11237 did not increase endogenous RAR beta mRNA levels in F9 embryonal carcinoma cells, even though it activated transcription of an RXR-responsive reporter gene in these cells. Thus, it is likely that RARs mediate the induction of RAR beta gene expression by RA. In contrast, the RXR-specific ligand induced rat growth hormone mRNA in GH3 pituitary cells, indicating that the effects of RA on growth hormone gene expression at least in part involve ligand binding to endogenous RXRs in vivo. Our results indicate that in addition to serving as cofactors for other nuclear hormone receptors, endogenous RXRs can function as ligand-dependent regulators of gene expression, i.e., classical nuclear hormone receptors. FAU - Davis, K D AU - Davis KD AD - Department of Medicine, University of Pennsylvania, Philadelphia 19104. FAU - Berrodin, T J AU - Berrodin TJ FAU - Stelmach, J E AU - Stelmach JE FAU - Winkler, J D AU - Winkler JD FAU - Lazar, M A AU - Lazar MA LA - eng GR - CA 40250/CA/NCI NIH HHS/United States GR - DK43806/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Benzoates) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoid X Receptors) RN - 0 (Retinoids) RN - 0 (Transcription Factors) RN - 146670-40-8 (SR 11237) RN - 5688UTC01R (Tretinoin) RN - 71441-28-6 (4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid) RN - 9002-72-6 (Growth Hormone) SB - IM MH - Animals MH - Benzoates/pharmacology MH - Cell Line MH - Gene Expression Regulation/drug effects MH - Growth Hormone/genetics MH - Pituitary Gland/drug effects/*metabolism MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Receptors, Cell Surface/*metabolism MH - Receptors, Cytoplasmic and Nuclear/drug effects/genetics/*metabolism MH - Receptors, Retinoic Acid/genetics/metabolism MH - Retinoid X Receptors MH - Retinoids/pharmacology MH - *Transcription Factors MH - Tretinoin/pharmacology PMC - PMC359244 EDAT- 1994/11/01 00:00 MHDA- 1994/11/01 00:01 PMCR- 1994/11/01 CRDT- 1994/11/01 00:00 PHST- 1994/11/01 00:00 [pubmed] PHST- 1994/11/01 00:01 [medline] PHST- 1994/11/01 00:00 [entrez] PHST- 1994/11/01 00:00 [pmc-release] AID - 10.1128/mcb.14.11.7105-7110.1994 [doi] PST - ppublish SO - Mol Cell Biol. 1994 Nov;14(11):7105-10. doi: 10.1128/mcb.14.11.7105-7110.1994.