The Metabolic Clearance Rates and Interconversion of Cortisol and Cortisone in Pregnant and Nonpregnant Baboons

Abstract

Pregnancy alters the pattern of maternal cortisol (F) metabolism and increases the maternal serum cortisol-binding capacity (CBC) of baboons. To determine whether these changes are associated with alterations in F clearance, the metabolic clearance rate (MCR) and interconversion (ρ) of F and cortisone (E) were measured by continuous infusion of [³H]F and [¹⁴C]E in 9 regularly menstruating and 7 pregnant baboons (Papio papio). In non-pregnant animals, the values ( ± se) for MCR-E (488 ± 48 l/day) were greater (P < 0.001) than those for MCR-F (214 ± 22 l/day). The p value for the conversion of E → F (62.8 ± 4.7%) was greater (P < 0.001) than that for the reaction F → E (41.6 ± 3.7%), indicating that F formation is favored. Consistent with MCR-E > MCR-F, the per cent of F bound to proteins other than albumin (75 ± 2) was greater (P < 0.001) than the per cent of E bound (52 ± 3). The production rate(MCR × peripheral concentration; μg/min) of F (55.1 ± 7.9) was greater (P < 0.001) than that of E (28.5 ± 3.9) with essentially all of the F being secreted directly (secretion rate 51.2 ± 7.9 μg/min). Essentially all of the E produced was derived from circulating F, virtually none being secreted directly (secretion rate 4.6 ± 3.9 μg/min). Pregnancy did not alter the MCR-F (190 ± 23 l/day), MCR-E (515 ± 51 l/day), per cent of F (79 ± 3), or per cent of E (49 ± 3) bound, or F (57.2 ± 9.2 μg/min) or E (35.5 ± 4.9 μg/min) production rates. CBC (μg F/100 ml) was significantly (P < 0.01) elevated (25.3 ± 2.3, nonpregnant vs 35.1 ± 1.6, pregnant). In addition, p E → F was increased (75.5 ± 1.8%) as was p F → E (54.3 ± 3.7%; P < 0.01). We have concluded that the MCR-F during pregnancy is more dependent on alterations in maternal metabolism than on the increased serum CBC characteristic of gestation. We suggest that the latter factor may be important in regulating the physiologic levels of the other steroids which bind to it.