The Mechanism of Hypercortisolemia in the Squirrel Monkey*

The squirrel monkey, a New World primate, has plasma cortisol levels roughly 12 times those in Old World primates, such as the cynomolgus monkey, and man. Two mechanisms are possible to maintain this high plasma cortisol level: an increased cortisol production rate (PR) and a decreased cortisol MCR. The cortisol MCR in the squirrel monkey is half that in the cynomolgus monkey [65 ± 3 vs. 123 ± 3 liters/M2- day (mean ± SE), respectively; P < 0.001]. The cortisol PR, however, is 6 times higher in the squirrel monkey than in the cynomolgus monkey (199 ± 21 vs. 32 ± 6 mg/M2• day; P< 0.001). The mild adrenal gland enlargement of the squirrel monkey (320 ± 22 us. 197 ± 10 mg adrenal/kg BW in the cynomolgus monkey; P < 0.001) does not appear to account entirely for the 6-fold increase in the cortisol PR. These findings suggest an increased cortisol biosynthetic efficiency in the squirrel monkey. This was examined by measuring the activity of four adrenal microsomal enzymes. 3β-Hydroxysteroid dehydrogenase-isomerase activities are similar in the squirrel and cynomolgus monkeys [10.5 ± 0.15 vs. 10.2 ± 0.51 nmol-min/mg protein (mean ± SE), respectively], whereas 17-hydroxylase activity is slightly higher in the cynomolgus monkey (10.5 ± 0.09 vs. 9.4 ± 0.52 nmol-min/mg protein in the squirrel monkey; P < 0.05). The activity of 21- hydroxylase, however, is 4 times higher in the squirrel monkey (23.9 ± 0.26 us. 6.4 ± 0.23 nmol-min/mg protein in the cynomolgus monkey; P < 0.001), and 17,20-desmolase activity is significantly lower in the squirrel monkey (24.7 ± 1.98 vs. 37.5 ± 1.86 pmol-min/mg protein in the cynomolgus monkey; P < 0.0025). Plasma ACTH concentrations are similar in squirrel and cynomolgus monkeys [8.6 ± 1.0 vs. 10.3 ± 4.0 pg/ml (mean ± SE), respectively]. We conclude that the squirrel monkey maintains high plasma cortisol levels mainly by an increased cortisol PR, which may be facilitated by alterations in the activity of the cortisol biosynthetic enzymes.