Estrogen and thyroid hormone interaction on regulation of gene expression.
Estrogen receptor (ER) and thyroid hormone receptors (TRs) are ligand-dependent nuclear transcription factors that can bind to an identical half-site, AGGTCA, of their cognate hormone response elements. By in vitro transfection analysis in CV-1 cells, we show that estrogen induction of chloramphenicol acetyltransferase (CAT) activity in a construct containing a CAT reporter gene under the control of a minimal thymidine kinase (tk) promoter and a copy of the consensus ER response element was attenuated by cotransfection of TR alpha 1 plus triiodothyronine treatment. This inhibitory effect of TR was ligand-dependent and isoform-specific. Neither TR beta 1 nor TR beta 2 cotransfection inhibited estrogen-induced CAT activity, although both TR alpha and TR beta can bind to a consensus ER response element. Furthermore, cotransfection of a mutated TR alpha 1 that lacks binding to the AGGTCA sequence also inhibited the estrogen effect. Thus, the repression of estrogen action by liganded TR alpha 1 may involve protein-protein interactions although competition of ER and TR at the DNA level cannot be excluded. A similar inhibitory effect of liganded TR alpha 1 on estrogen induction of CAT activity was observed in a construct containing the preproenkephalin (PPE) promoter. A study in hypophysectomized female rats demonstrated that the estrogen-induced increase in PPE mRNA levels in the ventromedial hypothalamus was diminished by coadministration of triiodothyronine. These results suggest that ER and TR may interact to modulate estrogen-sensitive gene expression, such as for PPE, in the hypothalamus.
Laboratory of Neurobiology and Behavior, Rockefeller University, New York, NY 10021, USA.
Y S
YS
Zhu
P M
PM
Yen
W W
WW
Chin
D W
DW
Pfaff
D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004745:Enkephalins / Q000235:genetics; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007016:Hypophysectomy; D007031:Hypothalamus / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics* / Q000502:physiology; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000502:physiology; D013937:Thymidine Kinase / Q000235:genetics; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000494:pharmacology
D004745:Enkephalins; D004967:Estrogens; D011498:Protein Precursors; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; C033660:preproenkephalin; D015500:Chloramphenicol O-Acetyltransferase; D013937:Thymidine Kinase