Molecular mechanisms of steroid hormone action

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Abstract
The ability of oestrogens and androgens to stimulate the growth of a number of endocrine cancers is well established and several endocrine therapies are widely used to reduce the availability of the hormones or to block their action. These include non-steroidal hormone antagonists such as tamoxifen and flutamide, steroidal compounds which include ICI 182780 and cyproterone acetate, and both steroidal and non-steroidal aromatase inhibitors. Although we have learned a great deal about the molecular mechanism of steroid hormone action, it is still unclear as to how hormones stimulate the proliferation of tumour cells and how hormone antagonists function. In part this is a result of the ability of oestradiol and testosterone to regulate the expression of many proteins implicated in the control of cell proliferation making it difficult to identify the crucial targets. Some of these targets are growth factors and/or their receptors which suggests that the mitogenic effects of steroids may be mediated by indirect autocrine or paracrine mechanisms (Clarke et al. 1991, Roberts and Sporn 1992). Alternatively since steroids regulate the expression of certain cyclins or kinase inhibitors (Musgrove and Sutherland 1994, Altucci et al. 1996) they may control cell cycle progression directly. Recent work suggests that as well as the cyclin D1 gene, cyclin D1 itself may be a crucial target (Zwijsen et al. 1997) but additional proteins could also be important in different subsets of tumours.

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