The utilization of placental substrates for cortisol synthesis by the baboon fetus near term

Abstract

We have determined the proportion of the in vivo cortisol (F) secretion rate (SRF) derived from circulating pregnenolone (P5) and progesterone (P4) in 9 baboon ( Papio papio) neonates, 5 (4 ♂, 1 ♀) delivered prior to the onset of labor by cesarean section (CS, 164–179 days) and 4 (2 ♂ , 2 ♀) delivered spontaneously at term (SD, 164–179 days; term = 184 days). The metabolic clearance rate (MCR; 1/d/kg) and production rates (PR; mg/d/kg) of P4 and P5 and transfer constants (p) for the reactions P5 → P4 14 P5 → F, and P4 → F, were determined by continuous infusion of [1,2- 3H] P5 and [4- 14C] P4. In CS animals the MCR-P5 (41.4 ± 5.6; X ± SE) was lower than the MCR-P4 (74.0 ± 8.5; P < 0.001). However, the pP5 → F (1.0% ± 0.3%) and pP4 → F (0.9% ± 0.3%) were similar although lower (P < 0.001) than pP5 → P4 (9.0% ±1.4%). The PR-P4 (7.0 ± 0.8) was 4–5 times greater than the PR-P5 (P < 0.01). In SD newborns, only the pP5 → F (3.4% ± 0.9%) and the PR-P4 (0.5 ± 0.2) were different (P < 0.01) from values in CS neonates. These results indicate that although the baboon fetus has the capacity to convert P5 to P4, the abundant quantities of P4 measured in fetal serum (95 ± 12 ng/ml) near term are primarily placental in origin. Moreover, the apparently low (< 5%) transfer constants for the conversion of P5 or P4 to F suggests minimal utilization of these circulating precursors for F synthesis. Indeed, the calculated proportion of the SR-F derived from circulating P4 was 5.3% ± 2.0% in CS neonates and only 0.3% ± 0.1% in SD newborns. In these animals, values for the utilization of circulating P5 were 1.4% ± 0.4% and 1.6% ± 0.4%, respectively. We conclude that endogenous adrenal substrates and not placental substrates are the primary precursors utilized for fetal adrenal F production in late baboon gestation.