The Metabolism of Cortisol by Term Baboon Neonates (Papio papio)

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Abstract
The metabolism of i.v. administered [4-14C]cortisol (F) was examined in 3 female, spontaneously delivered, term baboons <24 h old. Sixty and 80% of 14C was recovered in urine within 24 and 68 h, respectively. The distribution of urinary 14C was 44.7% unconjugated, 18.1% glucuronoside, 3.3% sulfate, and 24% unextractable with ethyl acetate. The metabolites were isolated by chromatography and crystallization. Eighty percent of unconjugated and 60% of glucuronoside metabolites were more polar than the cortols, the majority being unknown I (Rf 0.15), and unknown II (Rf 0.35), [cf., 6.beta.,11.beta.,17,21-tetrahydroxypregn-4-ene-3,20-dione (6.beta.-ol-F), Rf 0.44, ethyl acetate-chloroform-methanol-water, 25:75:50:50]. Unconjugated cortisol plus cortisone (E) represented <1% of urinary 14C and tetrahydrocortisone (THE) glucuronoside represented 1.2%. Excretion of tetrahydrocortisol (THF) and products of side-chain cleavage were negligible. Excretion of 20.beta.-hydroxy metabolites and 6.beta.-ol-F was .ltoreq.5% of urinary 14C. The cortisol production rate (mean .+-. SE) calculated from the specific activity of THE was 4.95 .+-. 1.92 mg/day. The glucuronoside/unconjugated 14C-ratio (0.4) contrasts with those previously reported in nonpregnant (4.0), pregnant (1.0) and postpartum (1.3) animals, indicating that the metabolic pattern in newborns is an exaggeration of that in pregnancy. In neonates, unknowns I and II compensate quantitatively for decreased glucuronoside excretion. Unknowns I and II are derivatives of THF and THE, suggesting that increased hydroxylase or deficient glucuronyl transferase, rather than impaired .DELTA.4-reductase, is responsible for decreased glucuronoside excretion. The low F production rate, reduced glucuronoside formation, and increase in highly polar compounds relative to nonpregnant adults resemble the situation in humans. However, the reduction in glucuronosides is compensated for, quantitatively, by highly polar metabolites, which are extractable from baboon urine with ethyl acetate but are nonextractable from the urine of human neonates.

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