Effects of chronic oestrogen replacement on stress-induced activation of hypothalamic-pituitary-adrenal axis control pathways

Oestrogen replacement therapy reportedly suppresses hypothalamic-pituitary- adrenal (HPA) axis responses to an emotional stressor in postmenopausal wom en. However, most studies in the rat suggest a facilitatory role for oestro gen in the control of HPA axis function. One explanation for this differenc e may be the regimen of oestrogen replacement: during oestrogen replacement therapy, oestrogen levels are low and constant whereas most animal studies examined the HPA axis response when oestrogen levels are rising. In the pr esent study, we assessed HPA axis stress responses in mature ovariectomized rats after plasma oestrogen levels had been maintained at physiological le vels for a prolonged period (25 or 100 pg/ml for 7 days). In the case of bo th an emotional stressor (noise) and a physical stressor (immune challenge by systemic interleukin-1 beta administration), oestrogen replacement suppr essed stress-related Fos-like immunolabelling, in hypothalamic neuroendocri ne cells and plasma adrenocorticotropin hormone responses. From the present data, and past reports, it appears unlikely that these effects of oestroge n are due to a direct action on corticotropin-releasing factor or oxytocin cells. Therefore, to obtain some indication of oestrogen's possible site(s) of action, Fos-like immunolabelling was mapped in the amygdala and in brai nstem catecholamine groups, which are neuronal populations demonstrating su bstantial evidence of involvement in the generation of HPA axis stress resp onses. In the amygdala, oestrogen replacement suppressed central nucleus re sponses to immune challenge, but not to noise. Amongst catecholamine cells, oestrogen replacement was more effective against responses to noise than i mmune challenge, suppressing A1 and A2 (noradrenergic) and C2 (adrenergic) responses to noise, but only A1 responses to immune challenge. These data s uggest that, as in postmenopausal women on oestrogen replacement therapy, c hronic low-level oestrogen replacement can suppress HPA axis stress respons es in the rat. Moreover, oestrogen appears to exert effects at multiple sit es within putative HPA axis control pathways, even though most of the relev ant neuronal populations do not contain genomic receptors for this gonadal steroid and the pattern of oestrogen action differs for an emotional vs a p hysical stressor.