The structure and function of steroid receptor proteins.
This review has highlighted several topics in the study of steroid hormone action. The unanswered questions regarding the mechanism of ligand-controlled LRF activity, the extent of evolutionary conservation and specificity of DNA binding, and the validity of various models of transcriptional regulation mediated through gene networks point to the future direction of research in this field. Steroid hormones are used extensively in clinical treatments, especially glucocorticoids. Our laboratory is attempting to determine which gene networks are responsible for some of these clinical phenotypes. Figure 5 points out that the study of glucocorticoid action holds a unique position because it spans both the basic sciences and the field of applied molecular biology. Now that we have a fundamental knowledge of the necessary elements required for steroid-dependent regulation of gene expression, we can better investigate the clinical responses to steroid therapy (which include devastating side effects) by isolating and characterizing the important target gene(s). In this author's opinion, future directions in the study of steroid responsiveness will have to include a systematic approach toward deciphering a variety of these LRF-regulated gene networks in experimentally feasible systems. Hopefully, work in this area may be revealing and perhaps beneficial to ongoing clinical studies. In addition, the study of mechanisms of transcriptional induction and repression, using the model system of LRFs, could be applicable to many gene regulatory systems which are controlled by such processes as development and differentiation.
Miesfeld
R L
RL
Department of Biochemistry, University of Arizona, College of Medicine, Tucson, Arizona.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013256:Steroids / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D011987:Receptors, Steroid; D013256:Steroids; D004247:DNA