Genome and hormones: Gender differences in physiology - Historical perspectives: An abridged history of sex steroid hormone receptor action

The field of steroid hormone action is well established, although it is bar ely more than four decades old. Pivotal experiments in the late 1950s and 1 960s showed that hormone-binding components exist within nuclei of target t issues and that steroid hormones act by regulating gene expression, rather than directly influencing enzymatic processes. The understanding that stero id hormone receptors interact with the general transcription machinery and alter chromatin structure came in the 1970s and 1980s, and details of this mechanism continue to be elucidated. In addition, the discovery of rapid ce llular responses to steroid hormones has led to the identification of putat ive membrane-bound steroid receptors that act without affecting gene transc ription. As noted in the recent Institute of Medicine report Exploring the Biological Contributions to Human Health: Does Sex Matter?, the effects of steroid hormones and defects in steroid hormone receptor action have a prof ound impact on human health and disease. Future research directives include the development of potent, selective steroid receptor modulators, the eluc idation of nongenomic steroid hormone effects, and further exploration of h ormone-genome interactions.