The metabolism of cortisol by term baboon neonates (Papio papio)

The metabolism of iv administered (4-14C)cortisol (F) was examined in 3 female, spontaneously delivered, term baboons less than 24th 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. Eight per cent 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), (csf., 6beta-ol-F), Rf 0.44, ethyl acetate-chloroofrmmethanol-water, 25:75:50:50). Unconjugated cortisol plus cortisone (E) represented less than 1% or urinary 14C and tetrahydrocortisone (THE) glucuronoside represented 1.2%. Excretion of tetrahydrocortisol (THF) and products of side-chain cleavage were negligible. Excretion of 20beta-hydroxy metabolites and 6beta-ol-F was less than or equal to 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, unknown 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 delta4-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 fo human neonates.