18-oxocortisol, a naturally occurring mineralocorticoid agonist

Two C-18-oxygenated corticosteroids, 18-hydroxy- and 18-oxocortisol, have recently been isolated from the urine of patients with primary and genetic (dexamethasone-suppressible) aldosteronism and from adrenal tissue. The relevance of these Steroids to the manifestations of mineralocorticoid excess in these disorders was investigated by measuring their affinity to rat renal corticosteroid receptors. 18-Oxocortisol showed greater affinity than the 18-hydroxy derivative for both mineralocorticoid and the glucocorticoid receptors and was accordingly assayed in vivo for mineralocorticoid activity. The 18-oxo derivative was found to be an agonist with a sodium-retaining and kaliuretic action qualitatively similar to that of aldosterone. Although 18-oxocortisol was one-third as active as 11-deoxycorticosterone in this assay, it was a more potent mineralocorticoid at the same total plasma concentration because of its lower affinity for corticosteroid-binding globulin.