Cortisol production and metabolism in the late gestation rhesus monkey fetus

Cortisol metabolism was studied in the pregnant rhesus monkey and her fetus at 135—140 days gestation using five long term catheterized fetal preparations. Two different isotope methods were used. The first method, employing simultaneous constant infusions of [³H]cortisol into the fetus and [¹⁴C]cortisol into the mother, demonstrated that the fetus had a significantly higher cortisol production rate than did the mother when expressed in terms of body weight (8.3 ± 1.6 vs. 3.4 ± 0.6 mg/kg-day). The fetus also had a higher cortisol MCR (76.7 ± 13.9 vs. 20.4 ± 5.4 liters/kg- day). The fetal adrenal secretion rate at this gestational age was not significantly different from the maternal rate (5.3 ± 1.9 vs. 3.2 ± 0.6 mg/kg-day, respectively). There was extensive transfer of cortisol in both directions across the placenta, with no net gain in cortisol for the fetus. However, at any particular time, 43.5% of the cortisol in the fetal circulation was derived from maternal secretion. In addition, 71.8% of fetal cortisone, a major metabolite and possible precursor of cortisol, was derived from maternal cortisol. The ³H to ¹⁴C ratios of cortisol and cortisone in the amniotic fluid and fetal and maternal circulations suggest that a large portion of amniotic fluid cortisol arises either directly from maternal cortisol or from cortisone in any of the three compartments. A bolus injection method, with computer analysis of the disappearance curve, also was used to estimate fetal cortisol production jrate (5.8 ± 0.8 mg/kg-day) and MCR (86.3 ± 5.2 liters/kg-day). These values were not significantly different from those determined in the constant infusion experiments. The fetal cortisol production rate was not significantly different from that in a group of seven infant monkeys during the first week of life (5.6 ± 1.2 mg/kg-day). Both the fetal and infant cortisol production rates were higher than those in a group of five healthy adult female monkeys (1.9 ± 0.7 mg/kg-day). Also, the fetal cortisol MCR was greater than that in the infant (27.1 ± 3.0 liters/kg-day) or the adult group (11.9 ± 1.8 liters/kg-day). The infant MCR was significantly greater than that in the adult. Analysis of the relative amounts of cortisone appearing after the bolus injection indicated that oxidation of cortisol to cortisone was a major method of clearance in the fetus and infant but was of much less importance in the nonpregnant adult. These data demonstrate that the late gestation fetal rhesus monkey actively secretes significant amounts of cortisol. The total amounts of cortisol produced in the fetus and infant are greater than that in the mother when expressed on the basis of body weight. Cortisol is cleared very rapidly from the fetus, due in large part to extensive feto-maternal transfer. There also is considerable oxidation of cortisol to cortisone in the fetus, and this metabolic pathway is preserved in the infant monkey. The regulation of fetal adrenal secretion, placental transfer, and interconversion of cortisol and cortisone are important factors in the control of fetal glucocorticoid activity.