Exposure to ovarian steroids elicits a female pattern of plasma cortisol levels in castrated male macaques

Our recent observations (1) that there is a difference in circadian patterns of plasma cortisol levels between male and female macaques and (2) that after gonadectomy these differences in the patterns and in the levels of cortisol were reduced prompted us to investigate how 17β-estradiol (E₂) and progesterone affect cortisol secretion in orchidectomized male rhesus macaques. Five male macaques, castrated as adults, were implanted subcutaneously with segments of silastic tubing filled with E₂ and with progesterone in a manner such that the levels and the sequence of these hormones mimicked those that occur during the menstrual cycle of intact female macaques. Since previous studies had shown that the difference in cortisol patterns was due to higher levels in females during the day, these studies were conducted from 0800 to 2000 hours. Blood samples were collected in an adjacent room at 15-minute intervals. Separate trials were conducted 2 weeks after E₂ was implanted and levels were 110 ±14 pg/ml and again 2 weeks later after progesterone was implanted and E₂ levels were 59 ± 15 pg/ml; progesterone levels averaged 4.0 ± 0.65 ng/ml. Mean plasma concentrations of cortisol (gmg/100 ml) for the 12-hour period were three-fold higher in orchidectomized males treated with E₂ (17.2) and with E₂ + progesterone (18.0) than in intact males (4.9). Levels in males treated with ovarian steroids were double that (8.5 μg/100 ml) observed for intact females. In intact male macaques, cortisol levels showed a steady decrease throughout the study period, whereas cortisol levels in intact females increased nearly three-fold to reach a peak near the midpoint of the light portion of the photoperiod before they decreased to reach a nadir at the end of the study. The pattern of change of cortisol levels throughout the 12-hour period in males treated with E₂ alone or with E₂ and progesterone was similar to the pattern observed in intact females. When the data are expressed as a percentage of the daily mean, the cortisol patterns observed in the orchidectomized groups treated with E₂ and progesterone were nearly identical to the pattern observed in intact females. The three-fold elevation in plasma cortisol in castrated male macaques occasioned by the administration of E₂ suggests that in primates, as has been found for nonprimate species, gonadal steroids have a dramatic influence on circulating levels of adrenal glucocorticoids. In addition, these data suggest that sex differences in the pattern of cortisol secretion are determined by activational rather than organizational actions of gonadal steroids.