Genetics of glucocorticoid receptors

The lymphocytolytic effect of glucocorticoids has been used for isolating receptor mutants. They fall into several groups with defects either in the hormone binding domain or the DNA binding domain or with part of the receptor polypeptide missing. These truncated receptors have increased binding affinity for general DNA and are synthesized from 5'-truncated messages. In addition, a phenotype has been identified in which a receptor allele, although apparently normal, is shut-off with no gene product detectable. The wild-type receptor polypeptide of about 95,000 molecular weight is synthesized from two mRNAs of 7 kb and 5 kb which differ in the lengths of their 3'-untranslated regions. A receptor model with three linearly arranged and functionally distinct domains is discussed. The DNA binding domain is rich in basic amino acids and cysteines and is located in the middle of the polypeptide. This region has the highest degree of homology with the estrogen receptor and with the v-erb-A oncogene product.