It is well known that normal growth and development of the reproductive tract depends on the proper stimulation by estrogen and other sex hormones. Likewise, it has been recognized for years that estrogenic stimulation provides an environment that is conducive to the development of neoplasia.1 The interrelationships between normal and abnormal estrogenic stimulation are not well understood. However, because of recent developments in biochemical and molecular biology, the mechanism of action of estrogen is beginning to be understood. In this article, we present some of these findings and relate them to normal and abnormal estrogeninduced growth.
At physiological temperatures, estrogen readily enters all cells (Fig. 1). In hormone-sensitive cells, estrogen is retained by binding to soluble macromolecules in the cytoplasm. These macromolecules are called cytosol receptors (Rc); while their exact nature in vivo is not known, they appear to be large proteins made up of two or more subunits. The binding reaction is specific for estrogens and results in the formation of receptor estrogen complexes (RcE) that undergo translocation to nuclear sites (RnE). The translocation process depletes the cytosol of Rc sites and these are subsequently replenished by mechanisms discussed below. Nuclear binding of the RnE complexes can be classified as either acceptor (A) or nonacceptor (NA) sites. Acceptor sites are generally visualized as a specific complex of chromosomal proteins, probably nonhistone proteins, that the RnE complex recognizes and binds to with a very high affinity. Nonacceptor sites are considered to be secondary sites on chromatin where the RnE complex can bind with a lower affinity.
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