Analyses of steroid receptors are important for understanding molecular details of transcriptional control, as well as providing insight as to how an individual transacting factor contributes to cell identity and function. These studies have led to the identification of a superfamily of regulatory proteins that include receptors for thyroid hormone and the vertebrate morphogen retinoic acid. Although animals employ complex and often distinct ways to control their physiology and development, the discovery of receptor-related molecules in a wide range of species suggests that mechanisms underlying morphogenesis and homeostasis may be more ubiquitous than previously expected.

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The steroid and thyroid hormone receptor superfamily

Two dimensional gel electrophoresis and computer analysis of proteins synthesized by clonal cell lines.

A secreted glycoprotein induced by estrogen in human breast cancer cell lines

Inhaled glucocorticosteroids have now become first-line therapy for the treatment of chronic asthma in many countries. They are the most effective asthma therapy currently available, and numerous studies have documented their long-term efficacy in asthma control in adults and in children. Inhaled steroids suppress inflammation in asthmatic airways, although their precise molecular mechanism of action is not yet certain. It is likely that steroids affect the transcription of several steroid-responsive genes, and, of particular importance, they may inhibit cytokine gene transcription and cytokine effects, thereby reducing the chronic inflammation in asthmatic airways. Inhaled steroids are now used at a much earlier stage in asthma therapy, and there is a strong argument for their early introduction in both adults and children to prevent asthma morbidity and mortality and possibly the structural changes resulting from uncontrolled chronic inflammation, which may lead to irreversible airflow obstruction in so...

Efficacy and safety of inhaled corticosteroids in asthma

The glucocorticoid receptor protein, in association with cognate hormonal ligands, binds with high affinity to specific DNA sequences termed glucocorticoid response elements (GREs) which can function as hormone-dependent transcriptional enhancers; thus, the receptor is a regulable enhancer-activating protein. We have constructed cell lines expressing different levels of glucocorticoid receptor, and demonstrate that the extent of a structural alteration in the chromatin at a characterized GRE, as well as the magnitude of several transcriptional responses elicited by the receptor, are roughly proportional to the number of receptor molecules per cell. Thus, for three independent glucocorticoid-responsive transcription units examined in our HTC-derived cell lines, the receptor appears to be a primary regulatory factor. Moreover, the results suggest that other cellular factors required for the assembly and function of GREs and transcription initiation complexes must be produced in excess relative to their levels of utilization at normal receptor concentrations.

Robert D. Ivarie

Papers

The glucocorticoid domain: steroid-mediated changes in the rate of synthesis of rat hepatoma proteins.