There are two key elements that regulate steroid hormone action, as summarized in Fig. 1. First, steroid hormones regulate gene transcription by binding to specific intracellular receptors. The receptors are structurally homologous members of the steroid/thyroid hormone receptor superfamily, and they act as ligand-dependent transcription factors to either activate or repress target gene expression (
1 ,
2 ). They regulate gene transcription by binding to hormone response element DNA sequences, either as homodimers or heterodimers, with the retinoid X receptor functioning as a common heterodimeric partner (
3 ,
4 ,
5 ). Therefore, the number of receptors and their binding affinity are important determinants of steroid action, as is the availability of ligand.
Fig. 1. The main steps required for steroid hormone gene activation. Circulating hormone is converted into the biologically active form, which then enters the target cell. This may occur by passive diffusion or endocytosis. The steroid then either travels to the nucleus to bind to its receptor, or if the receptor is cytosolic, the ligandreceptor complex translocates to the nucleus. Once in the nucleus, the steroid-receptor complexes bind to target gene DNA either as homodimers or as heterodimers, and in conjunction with a variety of accessory proteins, regulate target gene transcription.