6-Hydroxylation of cortisol and urinary 6beta-hydroxycortisol.

The 6β-hydroxylation of steroids in vivo, and under in vitro conditions, is well documented. Incubation studies have demonstrated that the human adrenal contains a C-6β-hydroxylase system which, after further investigation, was reported to be present in several other normal and neoplastic tissues. 6β-Hydroxycortisol was first isolated and identified from guinea-pig urine and, subsequently, in humans, following oral administration of cortisol in both cases, and was found to be the largest fraction of unconjugated steroid excreted in urine. This steroid was also excreted in elevated concentrations in late human pregnancy urine, and in newborn infants, as well as in liquor amnii of normal and pathologic pregnancies. Abnormally high levels of 6β-hydroxycortisol were present in some disease states, and it was also found that the excretion of this steroid increased after the administration of ACTH, thus showing its adrenal origin. Treatment with estrogens, and with certain drugs, has a marked effect in stimulating the metabolism of cortisol to 6β-hydroxycortisol, causing severalfold increases in the urinary excretion of this steroid in man. Since 6β-hydroxylation plays a significant role in the metabolism of cortisol in man, and with a view to studying the importance of this metabolic pathway, the most reliable index would appear to be the measurement of 6β-hydroxycortisol in urine, for which sensitive methods such as fluorimetric and radioimmunoassay procedures have recently become available. A method for the determination of the production rate measurement of 6β-hydroxycortisol has also been developed. This review has shown that the estimation of 6β-hydroxycortisol could be applied for the study of 6β-hydroxylase activity under various conditions, and to assess adrenocortical function in health and disease.