Diurnal steroid patterns during gestation in the rhesus macaque: Onset, daily variation, and the effects of dexamethasone treatment

Serum samples for cortisol, estradiol-17β (E₂), and progesterone analysis were obtained twice daily or more frequently to determine the onset of diurnal steroid patterns in the maternal circulation of pregnant rhesus monkeys. The expected a.m./p.m. fluctuations in serum cortisol (31.6/22.9 μg/dl) were evident from Day 25, whereas nocturnal elevations in progesterone (9.62 16.31 ng/ml) were demonstrable on Day 30, and diurnal increments in E₂ (283/138 pg/ml), coincident with those of cortisol, appeared about Day 40. Microscopic examination of fetal adrenals from rhesus embryos (ages 30 to 50 days) indicated that the gland differentiates and undergoes extensive development when diurnal E₂ release first appears. Administration of 1.0 mg of dexamethasone twice daily to pregnant animals on Days 124 to 130 was accompanied by 1) complete suppression of cortisol release, 2) loss of the diurnal E₂ pattern, which was associated with a marked reduction in serum E₂, and 3) eventual loss of the nocturnal elevation in serum progesterone without altering its basal levels. Simiar treatment earlier in gestation reduced serum levels of both cortisol and E₂ without influencing the diurnal serum patterns of these hormones or progesterone. These results support the concept that maternal estrogen levels depend on a functional fetal adrenal and further suggest the hypothesis that the inverse patterns in serum cortisol and progesterone are related to altered binding of progesterone to serum proteins as adrenal activity varies throughout the day. Further evidence supporting the hypothesis of steroid-serum protein interaction was the appearance of nocturnal increments in serum progesterone in ovariectomized animals treated with Silastic capsules containing progesterone and the absence of such increments in similarly treated ovariectomized animals after pituitary stalk section to suppress circadian adrenal activity. It is now clear that diurnal rhythms in serum E₂ and progesterone as well as cortisol are present during most of gestation in the rhesus macaque, but the physiological importance of such rhythms remains to be elucidated.