Metabolism of 2α- and 6β-Hydroxycortisol in Man: Determination of Production Rates of 6β-Hydroxycortisol With and Without Phenobarbital Administration

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Abstract
Tracer doses of tritiated 2α- and 6β-hydroxycortisol were administered together with 4-14C-cortisol to 2 normal 24- and 29-yr-old men. The unconjugated (extractable with ethyl acetate) tritium radioactivity was excreted in both cases in less than 24 hr. The fraction of the tritium injected dose recovered as unconjugated steroid, when urine was collected for 48 hr, was 52 and 59%, respectively. The corresponding fraction of the injected dose of 14C was 3.2 and 4.0%. The chromatographic patterns of the free steroid fractions in the 2 experiments indicated that the unmetabolized steroids constituted the major portion. The recovered 2α-hydroxycortisol (purified after dilution with carrier) contained 3H but no 14C, indicating that 2α-hydroxycortisol is not a peripheral metabolite of cortisol in man. Cumulative 3H and 14C specific activities of 6β-hydroxycortisol were determined in 3 schizophrenic women in otherwise good health with and without phenobarbital administration following the simultaneous injection of tritiated 6β-hydroxycortisol and 4-14C-cortisol. The 14C cumulative specific activities of the 6β-hydroxycortisol were significantly lower than those of the 3β,17,21-trihydroxypregnane-ll,20-dione, indicating an adrenal secretion of 6β-hydroxycortisol. From the ratios of the 14C to 3H in the urinary 6β-hydroxycortisol and in the injection solution, the fraction of the total cortisol produced which was converted to circulating 6β-hydroxycortisol (the cortisol to 6β-hydroxycortisol conversion factor ρf→6β–0h f) was determined. The ρ values (0.012, 0.015 and 0.007 in controls) were 2.9-, 4.6- and 6.6-fold higher, respectively, following phenobarbital administration. No significant change in the cortisol production rates was observed. The total production rates of 6β-hydroxycortisol in the untreated patients were 346, 562 and 382 μg/24 hr. Following drug treatment, the corresponding values increased to 1210, 1310 and 792, respectively.