Nuclear receptor coactivator function in reproductive physiology and behavior

Abstract

Gonadal steroid hormones act throughout the body to elicit changes in gene expression that result in profound effects on reproductive physiology and behavior. Steroid hormones exert many of these effects by binding to their respective intracellular receptors, which are members of a nuclear receptor superfamily of transcriptional activators. A variety of in vitro studies indicate that nuclear receptor coactivators are required for efficient transcriptional activity of steroid receptors. Many of these coactivators are found in a variety of steroid hormone-responsive reproductive tissues, including the reproductive tract, mammary gland, and brain. While many nuclear receptor coactivators have been investigated in vitro, we are only now beginning to understand their function in reproductive physiology and behavior. In this review, we discuss the general mechanisms of action of nuclear receptor coactivators in steroid-dependent gene transcription. We then review some recent and exciting findings on the function of nuclear receptor coactivators in steroid-dependent brain development and reproductive physiology and behavior.

FIG. 1

Mechanism of ER-mediated transactivation of PR gene. Estradiol binds to an inactive estrogen receptor (ER). The receptor then undergoes a conformational change that activates the receptor and allows it to dimerize with another active ER. The dimer complex translocates to the nucleus of the cell, where it binds to an estrogen-responsive element on target genes and initiates gene transcription. ERE, estrogen response element; SRC-1, steroid receptor coactivator-1; CBP, CREB binding protein; P/CAF, p300/CBP-associated factor; PR, progestin receptor.