The Estrogen Receptors and Their Multiple Gene Activation Mechanisms

The Estrogen Receptors and Their Multiple Gene Activation Mechanisms 

Estrogen receptors constitute the only known members of the family of steroid receptors that have multiple subtypes. This diversity of ERs offers unique possibilities for the modulation of estrogen-responsive genes. 

The human ER was first cloned and its structure determined from human breast cancer MCF-7 cells (Green et al., 1986 Greene et al., 1986). ERa consists of 595 amino acids separated into six functional domains (Kumar et al., 1987). Over the past decade, all studies to elucidate the molecular events underlying the mode of ER action as well as antiestrogen-designed therapies have focused on the ERa identified and cloned several years ago (Green et al., 1986 Greene et al, 1986 White et al, 1987). 

A most important question is the distribution of ERa and ERp in different tissues to explain the tissue-specific effects of estrogens and, especially, the new antiestrogens. ERp has a high level of expression in bone, prostate, hypothalamus, and specific areas in the central nervous system (Kuiper et al., 1996, 1997 Laflamme et al., 1998). As illustrated in Fig. 2, the ERa-E2 and ERp-E2 complexes can form homodimers (ERa-ERa and ERP-ERP) or heterodimers (ERa-ERP). Such a diversity of ERa and ERP interactions provides additional means of exerting gene-specific actions. 

Estrogen receptors are members of a family of ligand-inducible transcriptional regulators, which include steroids, thyroid hormones, retinoids, and vitamin D. 

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III. The Estrogen Receptors and Their Multiple Gene Activation Mechanisms. . 303... 

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