Acute Restraint Stress Increases Intrahypothalamic Oestradiol Concentrations in Conjunction with Increased Hypothalamic Oestrogen Receptor β and Aromatase mRNA Expression in Female Rats

Abstract

Activation of the hypothalamic-pituitary-adrenal axis is considered to be one of the key physiological responses to stress and, interestingly, shows a marked sex difference. Oestradiol plays an important role in this sex difference. The present study investigated the systemic and intrahypothalamic oestradiol response to physical restraint stress in female rats. We used jugular catheterisation and intrahypothalamic microdialysis to simultaneously measure plasma oestradiol and local oestradiol concentrations in the paraventricular nucleus (PVN) of the hypothalamus. We also assessed corticotrophin-releasing hormone (CRH), aromatase, and oestrogen receptor (ER) α and β mRNA expression in the PVN by quantitative polymerase chain reaction immediately after the acute stress period. As expected, PVN CRH mRNA and plasma corticosterone were significantly increased after acute stress. Interestingly, the local oestradiol concentration in the PVN also increased during the 1-h stress period in pro-oestrus and in ovariectomised (OVX) animals. Aromatase mRNA expression in the PVN was increased markedly in pro-oestrus but only modestly in oestrus. PVN ERβ but not ERα mRNA expression was significantly elevated in pro-oestrous animals. In addition, plasma oestradiol levels increased 10 min after stress, both during pro-oestrus and oestrus but not in OVX animals. To conclude, we report an intra-hypothalamic oestradiol response to restraint stress. The rising hypothalamic oestradiol concentration together with increased ERβ gene expression indicates a positive feedback of hypothalamic oestradiol signalling during acute stress in rats.