Gonadectomy Reverses The Sexually Diergic Patterns Of Circadian and Stress‐Induced Hypothalamic‐Pituitary‐Adrenal Axis Activity In Male and Female Rats

Abstract

Enhanced corticosterone release by female compared to male rats under basal and stress conditions is well documented. The demonstration that gonadectomy enhances stress-induced corticosterone secretion in male rats, but reduces such levels in female rats, suggests a causal association between gonadal steroids and corticosterone release. The present study examined the corticosterone profile of sham gonadectomized and gonadectomized female and male rats under basal and stress conditions. An automated sampling system collected blood from each freely moving, unanaesthetized rat every 10 min (i) over a 24-h period; (ii) following noise stress; and (iii) following an immune-mediated stress (lipopolysaccharide, LPS). Plasma was analysed for corticosterone content using radioimmunoassay. Castration resulted in a significant increase in basal corticosterone release compared to the sham-castrated male rats. Pulsar analysis revealed a significant two-fold increase in the number of corticosterone pulses over 24 h. Corticosterone increases in response to noise stress and to LPS injection were enhanced following castration. Conversely, ovariectomy resulted in a two-fold reduction in the number of corticosterone pulses as well as the stress response compared to sham-ovariectomized female rats. Arginine vasopressin (AVP), corticotrophin-releasing hormone (CRH) and glucocorticoid receptor mRNAs in the paraventricular nucleus and pro-opiomelanocortin (POMC) mRNA in the anterior pituitary were analysed post-LPS administration by in situ hybridization. Significantly higher values were found for AVP, CRH and POMC mRNAs examined for sham females and castrated males compared to sham males and ovariectomized females. This study confirms previous reports concerning the influence of gonadal factors in regulating HPA axis activity and stress responsiveness. The present results extend these observations to the regulation of the dynamic pattern of corticosterone release under basal conditions and suggests that this alteration in pulsatility is important for the differences in stress responsiveness when comparing males and females.

Sexually Dimorphic Responses of the Brain Norepinephrine System to Stress and Corticotropin-Releasing Factor

“…Previous studies documented an increased responsiveness of the HPA axis in female vs male rats (Kitay, 1961;Critchlow et al, 1963;Le Mevel et al, 1979;Seale et al, 2004). The present study is the first to demonstrate that, in parallel with the HPA axis, the brain NE system of female rats is more responsive to certain stressors.…”

“…This included greater levels of CRF receptor protein in the LC, increased neuronal sensitivity to CRF and differential regulation of CRF-LC interactions by prior stress in female vs male rats. Unlike the sex differences in HPA axis responsivity, which have been attributed to circulating hormones (Burgess and Handa, 1992;Miller et al, 2004;Seale et al, 2004), sex differences in LC sensitivity were independent of adult hormonal status. Given the role of the LC-NE system in arousal and attention (Aston-Jones et al, 2000), the present results predict that the expression of these aspects of the stress response will be enhanced in females.…”

“…To date, the focus has been on elements of the HPA axis. Although there is substantial evidence for such a sexual differentiation in HPA sensitivity in rats (Kitay, 1961;Critchlow et al, 1963;Le Mevel et al, 1979;Seale et al, 2004), this distinction is less clear in humans. Indeed, certain studies suggest that HPA drive is greater in males compared to females under certain conditions (Kirschbaum et al, 1999;Kudielka et al, 1998;Seeman et al, 2001;Traustadottir et al, 2003).…”

“…The higher incidence of depression in females has led to speculation that hormonal influences on components of the HPA axis may contribute to dysfunctions. In support of this, rodent studies have demonstrated elevated basal and stressinduced corticosterone secretion in female rats (Kitay, 1961;Critchlow et al, 1963;Le Mevel et al, 1979;Seale et al, 2004). Moreover, estrogen has been demonstrated to impair glucocorticoid negative feedback (Burgess and Handa, 1992).…”

“…Although sex differences in HPA sensitivity appear to be hormone-dependent (Kitay, 1961;Critchlow et al, 1963;Le Mevel et al, 1979;Seale et al, 2004), sex differences in LC sensitivity to stress are independent of adult hormonal status. Sex differences in the LC response could arise from direct organizational actions of hormones on expression of CRF-R or components of the CRF-R signaling pathway in LC neurons during development.…”