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Nuclear Receptor Coactivators Modulate Hormone-Dependent Gene Expression in Brain and Female Reproductive Behavior in Rats

Center for Neuroendocrine Studies and Neuroscience and Behavior Program (H.A.M., A.L.G., M.J.T.), University of Massachusetts, Amherst, Massachusetts 01003; Department of Physiology (A.P.A., M.M.M.), University of Maryland School of Medicine, Baltimore, Maryland 21201; and Department of Biology (M.J.T.), Skidmore College, Saratoga Springs, New York 12866

Address all correspondence and requests for reprints to: Marc J. Tetel, Ph.D., Department of Biology, Dana Science Center, Skidmore College, Saratoga Springs, New York 12866. E-mail: mtetel{at}skidmore.edu

Gonadal steroid hormones act in the brain to elicit changes in gene expression that result in profound effects on behavior and physiology. A variety of in vitro studies indicate that nuclear receptor coactivators are required for efficient transcriptional activity of steroid receptors. Two nuclear receptor coactivators, steroid receptor coactivator-1 (SRC-1) and cAMP response element binding protein-binding protein (CBP), have been shown to act in concert to enhance ER activity in vitro. In the present study, we investigated the function of these important nuclear receptor coactivators in estrogen action in rodent brain. Reduction of SRC-1 and CBP protein in brain disrupted ER-mediated activation of the behaviorally relevant progestin receptor gene. Furthermore, we found that SRC-1 and CBP function in brain to modulate the expression of hormone-dependent female sexual behavior. These findings indicate that these nuclear receptor coactivators function in brain to modulate ER transcriptional activity and the expression of hormone-dependent behavior.

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