Tissue-Specific Regulation of Genes by Estrogen Receptors

Dale C. Leitman; Sreenivasan Paruthiyil; Chaoshen Yuan; Candice B. Herber; Moshe Olshansky; Mary Tagliaferri; Isaac Cohen; Terence P. Speed

doi:10.1055/s-0031-1299593

Seminars in Reproductive Medicine, Table of Contents

Semin Reprod Med 2012; 30(01): 14-22
DOI: 10.1055/s-0031-1299593

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Tissue-Specific Regulation of Genes by Estrogen Receptors

Authors

Dale C. Leitman

¹Department of Nutritional Science and Toxicology
Sreenivasan Paruthiyil

³Bionovo Inc., Emeryville, California
Chaoshen Yuan

¹Department of Nutritional Science and Toxicology
Candice B. Herber

¹Department of Nutritional Science and Toxicology
Moshe Olshansky

⁴Division of Bioinformatics, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Mary Tagliaferri

³Bionovo Inc., Emeryville, California
Isaac Cohen

³Bionovo Inc., Emeryville, California
Terence P. Speed

⁴Division of Bioinformatics, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

²Department of Statistics, University of California, Berkeley, California

Abstract

Estrogens are frequently used in reproductive medicine. The Women’s Health Initiative trial found that the risks of menopausal hormone therapy (MHT) exceed the benefits. The estrogens in MHT, however, were introduced prior to our understanding of the mechanism of action of estrogens. Estrogen signaling is highly complex, involving various DNA regulatory elements to which estrogen receptors bind. Numerous transcription factors and co-regulatory proteins modify chromatin structure to further regulate gene transcription. With a greater understanding of estrogen action, the major problem with the current estrogens in MHT appears to be that they are nonselective. This produces beneficial effects in bone, brain, and adipose tissue but increases the risk of breast and endometrial cancer and thromboembolism. Resurrecting MHT for long-term therapy will require the development of more selective estrogens, such as estrogen receptor (ER)β-selective estrogens and tissue-selective ERα agonists. These compounds will offer the best prospects to expand the indications of MHT and thus prevent the chronic conditions associated with menopause.

Keywords

estrogen - estradiol - estrogen receptor - gene regulation - transcription

Full Text

References

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