Current models of steroid hormone action: a critique

Abstract

In this review, we have traced the path of estradiol from its entry into the cell to the time of its release from the receptor. We feel that all of the current models are limited in one respect or another. We have examined most critically those currently most in vogue. The entry of estradiol into the cell is widely assumed to be simply a matter of diffusion. We have highlighted data that suggest the existence of a protein-mediated transport, but feel that the available data are too limited to make a definite conclusion.

PIP: Literature on the action of steroid hormone action is critically rev iewed. The entry of steroid hormones into the cell, the nature of the cytoplasmic receptor, steroid-induced changes in the cytoplasmic recepto r, the translocation of the receptor from cytoplasm to nucleus, the interaction of steroid receptors with nuclear components, the dissociati on of steroids from receptor sites and the tissue reponses to steroid hormones and their relationship to receptors are discussed. The data suggest that the entry of estradiol into the cell is protein-mediated, though the evidence is not conclusive. All of the current models of the entry of estradiol into the cell are considered limited in 1 regard or another. In that virtually every component of the nucleus has the properties of an acceptor, an acceptor model of the translocation of the receptor from the cytoplasm to the nucleus appears more accurate than a model involving the interaction of hormone-receptor complexes with high-affinity nuclear binding sites. A recent model, in which numerous low-affinity binding sites mask a few high-affinity binding sites, appears to more closely fit experimental results. Attention is drawn to the need for a better understanding of the fate of the receptor once it has acted to alter gene transcription. The data also suggest that differences exist between the actions of different steroid hormones, and research into these differences is encouraged.