Accessibility navigation

Differential interaction of estrogen receptor and thyroid hormone receptor isoforms on the rat oxytocin receptor promoter leads to differences in transcriptional regulation

Vasudevan, N., Davidkova, G., Zhu, Y. S., Koibuchi, N., Chin, W. W. and Pfaff, D. (2001) Differential interaction of estrogen receptor and thyroid hormone receptor isoforms on the rat oxytocin receptor promoter leads to differences in transcriptional regulation. Neuroendocrinology, 74 (5). pp. 309-24. ISSN 0028-3835

[img] Text - Published Version
· Restricted to Repository staff only
· The Copyright of this document has not been checked yet. This may affect its availability.


It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

Official URL:


Both the estrogen receptor (ER) and thyroid hormone receptor (TR) are members of the nuclear receptor superfamily. Two isoforms of the ER, alpha and beta, exist. The TRalpha and beta isoforms are products of two distinct genes that are further differentially spliced to give TRalpha1 and alpha2, TRbeta1 and beta2. The TRs have been shown to interfere with ER-mediated transcription from both the consensus estrogen response element (ERE) and the rat preproenkephalin (PPE) promoter, possibly by competing with ER binding to the ERE or by squelching coactivators essential for ER-mediated transcription. The rat oxytocin receptor (OTR) gene is thought to be involved in several facets of reproductive and affiliative behaviors. 17beta-Estradiol-bound ERs upregulate the OTR gene in the ventromedial hypothalamus, a region critical for the induction of lordosis behavior in several species. We investigated the effects of the ligand-binding TR isoforms on the ER-mediated transcription from a physiological promoter of a behaviorally relevant gene such as the OTR. Only ERalpha could induce the OTR gene in two cell lines tested, the CV-1 and the SK-N-BE2C neuroblastoma cell lines. ERbeta was incapable of inducing the gene in either cell line. ERalpha is therefore not equivalent to ERbeta on this physiological promoter. Indeed, in the neural cell line, ERbeta can inhibit ERalpha-mediated induction from the OTR promoter. While the TRalpha1 isoform inhibited ERalpha-mediated induction in the neural cell line, the TRbeta1 isoform stimulated induction, thus demonstrating isoform specificity in the interaction. The use of a DNA-binding mutant, the TR P box mutant, showed that inhibition of ERalpha-mediated induction of the rat OTR gene promoter by the TRalpha1 isoform does not require DNA-binding ability. SRC-1 overexpression relieved TRalpha1-mediated inhibition in both cell lines, suggesting that squelching for coactivators is an important molecular mechanism in TRalpha-mediated inhibition. Such interactions between TR and ER isoforms on the rat OTR promoter provide a mechanism to achieve neuroendocrine integration.

Item Type:Article
Divisions:No Reading authors. Back catalogue items
ID Code:58916
Uncontrolled Keywords:Animals Cell Line DNA-Binding Proteins/physiology Estradiol/pharmacology Estrogen Receptor alpha Gene Expression Regulation/physiology Mutation/physiology Promoter Regions, Genetic/drug effects/*physiology Protein Isoforms/physiology Rats Receptors, Cytoplasmic and Nuclear/physiology Receptors, Estrogen/*physiology Receptors, Oxytocin/*genetics Receptors, Thyroid Hormone/genetics/*physiology Response Elements/physiology Transcription, Genetic/*physiology

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation