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Parallelism of 11β- and 18-Hydroxylation Demonstrated by Urinary Free Hormones in Man^*

Pharmacologisches Institut, Universitdts Heidelberg Heidelberg 6900, Federal Republic of Germany
Division of Pediatric Endocrinology, Department of Pediatrics, The New York Hospital-Cornell Medical Center New York, New York 1002

Address requests for reprints to: Dr. Lenore S. Levine, Department of Pediatrics, The New York Hospital-Cornell Medical Center, 525 East 68th Street, New York, New York 10021.

To investigate whether the functions of 11β- and 18-hydroxylase are parallel in the human adrenal cortex, we measured urinary free deoxycorticosterone (DOC), free 18-hydroxy- DOC (18-OH-DOC), and free corticosterone (B) in 22 subjects (aged 36/12 to 19 yr) before and after metyrapone administration and ACTH infusion. The substrate to product ratio was used as an index of enzyme activity. There were parallel changes in the ratios of DOC to B (lβ-hydroxylase) and DOC to 18-OHDOC (18-hydroxylase) in all conditions, while the B to 18-OHDOC ratio (product ratio) was relatively constant. The correlations between the ratios of DOC to B and DOC to 18-OH-DOC as well as between B and 18-OH-DOC were highly significant under all conditions (r = 0.89; P = 0.00001). These findings are consistent with previous in vitro studies and studies in patients with congenital adrenal hyperplasia due to lβ-hydroxylase deficiency, suggesting that a single enzyme system is responsible for both 11β- and 18-hydroxylation of DOC in the adrenal zona fasciculata.

As part of the metyrapone study, 18-OH-B was measured: 18- OH-B values decreased significantly, and the B to 18-OH-B ratio increased during metyrapone administration (from 0.38 ± 0.09 to 1.79 ± 0.04; P µ 0.005), showing inhibition of 18-hydroxylation of B as well. Since 18-OH-B was suppressed without a decrease in PRA, we concluded that this inhibition is a primary metyrapone effect and not the result of increased DOC and suppressed PRA.

^* This work was supported in part through NIH Awards HD-00072 and HL-17749 and through a grant (RR47) from the General Clinical Research Centers Program of the Division of Research Resources, NIH.

Received November 30, 1979.