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Estrogen and thyroid hormone interaction on regulation of gene expression.

Publication ,  Journal Article
Zhu, YS; Yen, PM; Chin, WW; Pfaff, DW
Published in: Proc Natl Acad Sci U S A
October 29, 1996

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.

Duke Scholars

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

October 29, 1996

Volume

93

Issue

22

Start / End Page

12587 / 12592

Location

United States

Related Subject Headings

  • Triiodothyronine
  • Transcription, Genetic
  • Thymidine Kinase
  • Receptors, Thyroid Hormone
  • Receptors, Estrogen
  • Rats
  • RNA, Messenger
  • Protein Precursors
  • Promoter Regions, Genetic
  • Hypothalamus
 

Citation

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Zhu, Y. S., Yen, P. M., Chin, W. W., & Pfaff, D. W. (1996). Estrogen and thyroid hormone interaction on regulation of gene expression. Proc Natl Acad Sci U S A, 93(22), 12587–12592. https://doi.org/10.1073/pnas.93.22.12587
Zhu, Y. S., P. M. Yen, W. W. Chin, and D. W. Pfaff. “Estrogen and thyroid hormone interaction on regulation of gene expression.Proc Natl Acad Sci U S A 93, no. 22 (October 29, 1996): 12587–92. https://doi.org/10.1073/pnas.93.22.12587.
Zhu YS, Yen PM, Chin WW, Pfaff DW. Estrogen and thyroid hormone interaction on regulation of gene expression. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12587–92.
Zhu, Y. S., et al. “Estrogen and thyroid hormone interaction on regulation of gene expression.Proc Natl Acad Sci U S A, vol. 93, no. 22, Oct. 1996, pp. 12587–92. Pubmed, doi:10.1073/pnas.93.22.12587.
Zhu YS, Yen PM, Chin WW, Pfaff DW. Estrogen and thyroid hormone interaction on regulation of gene expression. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12587–12592.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

October 29, 1996

Volume

93

Issue

22

Start / End Page

12587 / 12592

Location

United States

Related Subject Headings

  • Triiodothyronine
  • Transcription, Genetic
  • Thymidine Kinase
  • Receptors, Thyroid Hormone
  • Receptors, Estrogen
  • Rats
  • RNA, Messenger
  • Protein Precursors
  • Promoter Regions, Genetic
  • Hypothalamus