Identification of a mineralocorticoid receptor binding substance in the urine of patients with congenital adrenal hyperplasia

Increased amounts of circulating mineralocorticoid receptor binding substances presumed to be natural antagonists were previously demonstrated in congenital adrenal hyperplasia. In this study the feasibility of using urinary extracts for the identification of such binding substances was investigated. Urinary extracts from patients with the 21-hydroxylase defect did contain greater than normal amounts of mineralocorticoid receptor binding material. When subjected to Chromatographic separation using a radioreceptor assay to follow the course of fractionation, a major aldosterone binding competitor was identified. On the basis of its Chromatographic mobility in comparison with the labeled steroid, radioimmunoassay, ultraviolet absorption and radio-receptor assay of the native and acetylated derivative, the component was identified as 11-deoxycorticosterone and its structure confirmed by mass spectrometry. Although the major mineralocorticoid receptor binding component proved not to be an antagonist but an agonist, the results are in keeping with other evidence for overproduction of 11-deoxycorticosterone in the simple virilizing form of the disorder. Our finding did not disprove the existence of a circulating mineralocorticoid antagonist in congenital adrenal hyperplasia, but demonstrate that the major receptor binding substance in urinary extracts in that disorder is the mineralocorticoid agonist, 11-deoxycorticosterone.