Nongenomic Actions of Steroid Hormones in Reproductive Tissues*

Abstract

THE STEROID hormone receptor superfamily includes glucocorticoid, mineralocorticoid, progestin, estrogen, androgen, and 1α,25-dihydroxyvitamin D3 receptors. All members of this superfamily share similar structural and functional characteristics and have highly conserved structural domains involved in DNA and ligand binding. The activation of steroid hormone receptors regulates the transcriptional activity of specific genes, thus mediating the so-called classic, or genomic, actions of steroids. A detailed description of the structure and function of the classic steroid receptors is beyond the scope of this review and has already been published (see reviews in Refs. 1–5). Briefly, within the intact cell the unoccupied form of the classic steroid receptor resides in the nucleus or in the nucleus and cytoplasm, dependent on the receptor and cell type. Steroid hormones act in the target tissues with a mechanism that may be summarized in the following steps: 1) free steroid enters the target cell by passive diffusion through the plasma membrane, passes through the nuclear membrane (in the case of nuclear receptors), and binds with high affinity to the receptor; 2) the steroid-receptor complex undergoes activation, a process that involves conformational changes (tertiary and quaternary structure) and enables the receptor to bind to selective sites on the chromatin; 3) the activated steroid-receptor complex interacts with specific DNA sequences referred to as steroid response elements, usually located upstream of the steroid-responsive genes; 4) the activated steroid-receptor complex acts as a transcription factor modulating the synthesis of specific mRNAs and proteins, in turn responsible for the final effect of the hormone.