Circadian Variation in Basal Plasma Corticosterone and Adrenocorticotropin in the Rat: Sexual Dimorphism and Changes across the Estrous Cycle*

Abstract

Sexual dimorphism in the rat hypothalamic-pituitary-adrenal axis was investigated by determination of plasma corticosterone and immunoreactive (I-) ACTH in males and in females at each stage of the estrous cycle. A serial blood-sampling technique enabled assessment of covariation of the two hormones across the full circadian range of their concentrations within individual animals. Distinct diurnal rhythms in plasma corticosterone were evident in all rats, and the degree and timing of this rhythmicity, determined by cosinor analyses, did not vary with gender or cycle stage. There were, however, marked differences in absolute levels of corticosterone across the estrous cycle, with the average daily concentration (mesor) increasing progressively from a minimum at estrus (129 Ϯ 11 ng/ml) to a maximum 3 days later at proestrus (246 Ϯ 14 ng/ml). The mesor corticosterone value in male rats (102 Ϯ 21 ng/ml) was not different from that in estrous females, but was lower than that in females at all other stages of the cycle. In contrast, no gender-or cycle-related differences were detected in absolute levels of I-ACTH, although distinct diurnal rhythms, synchronous with those for corticosterone, were evident in all groups. Accordingly, a strong and positive within-rat relationship between plasma corticosterone and I-ACTH was observed in all groups, but there was a clear shift in the nature of this relationship across the estrous cycle, such that the slope (i.e. concentration of plasma corticosterone per unit concentration of I-ACTH) was minimal in males and estrous females and maximal in proestrous females. In conclusion, this study shows that the extent of sexual dimorphism in resting plasma corticosterone levels is dependent on estrous cycle stage, being absent at estrus and maximal at proestrus. Moreover, this variation in plasma corticosterone was not accompanied by corresponding changes in plasma I-ACTH, suggestive of cycle-related changes in responsiveness of the adrenal cortex to trophic stimulation. (Endocrinology 138: 3842-3848, 1997) S EXUAL DIMORPHISM is a feature of the rat hypothalamic-pituitary-adrenal (HPA) axis, with higher plasma corticosterone levels consistently reported for female compared with male rats (1-8). This sex difference appears most pronounced at the peak of the circadian rhythm (1, 3, 4, 7) and is thought to reflect activation of the HPA axis by ovarian estrogen (1, 6, 9, 10). Accordingly, several studies have also identified changes in plasma corticosterone associated with estrous cycle stage, with peak corticosterone levels highest at proestrus (11-13), the time of maximal estrogen secretion (14). Interestingly, previous reports on gender differences in the rat HPA axis (2-8) have considered females as a single group with apparently no account taken of stage, length, or regularity of estrous cycles. Thus, it is possible that sexual dimorphism in plasma corticosterone occurs only when females are at those stages of the cycle when estrogen levels are high.Several previous studies ind...

Pregnancy-induced adaptations of the central circadian clock and maternal glucocorticoids

“…This apparent decoupling of circulating ACTH and corticosterone suggests that factors outside the conventional HPA axis influence plasma corticosterone in pregnancy. For example, enhanced adrenal responsiveness appears to drive increased maternal corticosterone levels after mid-gestation in the rat (Atkinson & Waddell 1995), an effect likely mediated via rising estrogen levels (Atkinson & Waddell 1997, Figueiredo et al 2007). Other 'non-HPA axis' factors that could enhance maternal levels of corticosterone include a fall in its metabolic clearance rate due to higher plasma corticosteroid-binding globulin (CBG) levels (Gala & Westphal 1967, Douglas et al 2003 or a contribution from the fetal adrenal.…”

Sleep deprivation inhibits adult neurogenesis in the hippocampus by elevating glucocorticoids

“…Typically, sleep occurs during periods of the diurnal rhythm when CORT levels are reduced (28,29). However, several lines of evidence argue against this possibility.…”

Faecal corticosterone metabolite assessment in socially housed male and female Wistar rats

“…It has been demonstrated that rats show a strong preference for solid floor compared with grid floor cage (38). Other studies show that housing rats on grid floor cages induce tactile hypersensitivity and nerve injury in the hind feet (39) and can also increase plasma level of corticosterone, blood pressure, heart rate and body temperature (40). Thus, this housing condition could alter faecal hormone metabolite assessment in rats.…”