Oestrogen augments the fetal ovine hypothalamus- pituitary-adrenal axis in response to hypotension.

In the fetal sheep, parturition is triggered by an increase in the activity of the fetal hypothalamus- pituitary-adrenal (HPA) axis which, in turn, augments the biosynthesis of oestrogen by the placenta. Parturition can be prevented or delayed by destruction of the paraventricular nucleus (PVN), pituitary or adrenal, or stimulated by infusions of adrenocorticotropin (ACTH) or glucocorticoids. We have previously reported that physiological increases in fetal plasma concentrations of oestradiol have a neuroendocrine effect to increase both basal and hypotension-stimulated ACTH secretion. The present study was performed to test the effect of oestradiol on the central baroreceptor and chemoreceptor reflex pathways. We used immunohistological techniques to identify various neuroanatomical regions which are activated by hypotension and, subsequently, those areas modified by oestrogen's action and baroreceptor and chemoreceptor denervation. We assessed cellular activation in these brain regions by immunostaining for Fos, the protein product of c-fos, an immediate early response gene. We found that oestradiol increased Fos abundance in nucleus tractus solitarius (NTS), rostral ventrolateral medulla (RVLM), and PVN, and augmented the increase in Fos in these regions in response to a 10 min period of brachiocephalic arterial occlusion (BCO). Carotid sinus denervation blocked the Fos response to BCO, but not to oestrogen alone, in these regions. In contrast, the hippocampus responded to BCO with increase Fos in intact fetuses, but did not respond to oestrogen treatment. None of the treatments altered Fos expression in cerebral cortex or in cerebellum. We conclude that oestradiol augments the activity of the central baroreceptor and chemoreceptor reflex pathways, and that it may influence fetal ACTH secretion via this site of action.