Testosterone-dependent variations in plasma and intrapituitary corticosteroid binding globulin and stress hypothalamic-pituitary-adrenal activity in the male rat

Abstract

Hypothalamic-pituitary-adrenal (HPA) activity is governed by glucocorticoid negative feedback and the magnitude of this signal is determined, in part, by variations in plasma corticosteroid-binding globulin (CBG) capacity. Here, in gonadectomized male rats we examine the extent to which different testosterone replacement levels impact on CBG and HPA function. Compared with gonadectomized rats with low testosterone replacement ( 2 ng/ ml), plasma adrenocorticotropin and -endorphin/ -lipotropin responses to restraint stress were reduced in gonadectomized rats with high testosterone replacement ( 5 ng/ml). Plasma CBG levels also varied negatively as a function of testosterone concentration. Moreover, glucocorticoid receptor binding in the liver was elevated by higher testosterone replacement, suggesting that testosterone acts to enhance glucocorticoid suppression of CBG synthesis. Since pituitary intracellular CBG (or transcortin) is derived from plasma, this prompted us to examine whether transcortin binding was similarly responsive to different testosterone replacement levels. Transcortin binding was lower in gonadectomized rats with high plasma testosterone replacement ( 7 ng/ml) than in gonadectomized rats with low testosterone replacement ( 2 ng/ml). This testosterone-dependent decrease in pituitary transcortin was associated, in vitro, with an enhanced nuclear uptake of corticosterone. These findings indicate that the inhibitory effects of testosterone on corticotrope responses to stress may be linked to decrements in plasma and intrapituitary CBG. This could permit greater access of corticosterone to its receptors and enhance glucocorticoid feedback regulation of ACTH release and/or proopiomelanocortin processing.

Estrogen receptor beta in the brain: From form to function

“…In males, gonadectomy increases stress-induced CORT and ACTH, and is reversible with testosterone or dihydrotestosterone (DHT) treatment (Bingaman et al, 1994;Handa et al, 1994a;Handa et al, 1994b;Viau and Meaney, 1996;Suzuki et al, 2001;Viau et al, 2003;Viau and Meaney, 2004). Furthermore, treatment of gonadectomized male rats with estrogen increases stress-induced c-fos mRNA, CRH hnRNA, AVP hnRNA, and CORT, whereas DHT treatment inhibits the response when compared to control animals (Lund et al, 2004b).…”

An alternate pathway for androgen regulation of brain function: Activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5α-androstane-3β,17β-diol

“…Whereas estradiol treatment appears to enhance, and testosterone treatment inhibits HPA reactivity, the mechanisms by which testosterone and estradiol act to influence HPA function have not been completely resolved. Evidence of estradiol and testosterone acting at the adrenal gland (Kitay 1965), anterior pituitary (Coyne and Kitay, 1969, 1971, Viau and Meaney, 2004 and hypothalamus (Viau and Meaney, 1996;Viau et al, 2003 has been reported. Although contributions of each level of the axis likely mediate the sex differences in HPA function, in this review we will focus our attention on the hypothalamic effects of the androgenic component of this regulation.…”

From killer to carer: steroid hormones and paternal behaviour

“…It is important to note however, the interacting relationship between the HPG axis and the hypothalamic-pituitary-adrenal (HPA) axis, controlling the secretion of glucocorticoids. Experimental evidence in male rats suggests a regulatory link between the HPG and HPA axes where increased HPG activity suppresses the HPA and vice versa (Monder et al 1994;Viau and Meaney 2004); however, in other species there does not seem to be such a strong regulatory response (Bercovitch and Clarke 1995;Robbins and Czekala 1997;Strier et al 1999). …”