Steroid hormones regulate growth and development in certain types of cells and are involved in a wide variety of physiological responses in most tissues. These responses depend on the association of a hormone with a receptor protein and the subsequent activation of different genes at precise stages during embryonic development and cell differentiation. The primary role of the steroid receptor complex is to bind to specific loci in the genome and regulate rates of gene transcription, but in addition steroids can also modulate the expression of some genes posttranscriptionally. The nuclear binding sites are specific DNA sequences termed steroid response elements that, upon steroid binding, function as transcriptional enhancers. After this interaction there are specific changes in the structure of chromatin which correlate with transcription of the gene and may mediate the action of the steroid. There are a variety of transcriptional enhancers associated with certain genes which interact with activating proteins and these could account for the expression of different networks of genes in individual cells that respond to different physiological stimuli.
Bronchial hyperresponsiveness is seen in a variety of disorders other than asthma, such as smoking-induced chronic airflow limitation, congestive heart failure, sarcoidosis, cystic fibrosis, and bronchiectasis, as well as in siblings of asthmatics and in people with allergic rhinitis. 19 In these situations, the methacholine test can be falsely positive, and one should interpret the results in the context of the clinical history.
* Dr. Lang has disclosed that he has received honoraria or consulting fees for teaching, speaking, consulting, or serving on advisory committees or review panels for the AstraZeneca, Critical Therapeutics, Dey, Genentech GlaxoSmithKline, Merck, Novartis, Schering/Key, Teva, and Verus corporations.