Abstract
In addition to the classic mechanism of steroid action mediated by binding to nuclear receptors, there is a growing body of evidence that steroids also exert rapid, nongenomic actions that are initiated at the cell surface by binding to specific steroid membrane receptors. However, the lack of information on the molecular structures of any steroid membrane receptors has impeded development of this alternative model of steroid hormone action. One of the best characterized models of nongenomic steroid action is the progestin induction of oocyte maturation (OM) in fish and amphibians via activation of plasma membrane progestin receptors (mPRs) on oocytes. Investigations of the marked changes in mPR abundance during OM in fishes have provided the first clear evidence of hormonal regulation of steroid membrane receptors and its physiological importance. Recently, a novel gene was discovered in the ovaries of spotted seatrout whose protein has the characteristics of an mPR and the intermediary in the progestin induction of oocyte maturation in this species. The putative mPR is also detected on seatrout sperm by Western blot analysis and is likely the mPR previously characterized in this species that mediates progestin initiation of sperm hyperactivity. Both structural and functional studies suggest the seatrout mPR is a G-protein coupled receptor (GPCR). Subsequently, thirteen structurally-related cDNAs were identified in other vertebrate species, and several of them were also shown to have characteristics of mPRs. The discovery of the molecular structure and likely orientation in the plasma membrane of this new class of steroid membrane receptors provides a plausible mechanistic explanation of how steroids acting at the cell surface can cause rapid intracellular responses. Membrane receptors for estrogens (mER) and androgens (mAR) have also been characterized in teleost gonads. In addition, the first clear evidence for endocrine disruption of a nongenomic steroid action by binding to a membrane steroid receptor was obtained with the seatrout mPR. Thus fish are valuable models for investigating nonclassical steroid actions and their interference by environmental contaminants.
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