Noradrenergic facilitation of the adrenocorticotropin response to stress is absent during lactation in the rat

Abstract

During lactation, the regulation of the activity of the hypothalamic-pituitary-adrenal (HPA) axis is modified in that tonically elevated glucocorticoid secretion is observed together with blunted ACTH secretion following exposure to various stressors. Although decreased CRF mRNA levels have been reported in neurons of the paraventricular nucleus (PVN) which control ACTH secretion, the mechanisms underlying stress hyporesponsiveness during lactation are still largely unknown. In addition, lactation is associated with inhibition of reproductive functions and the involvement of the PVN neurons in this inhibition is unclear. In these studies, we tested the hypothesis that the effects of stimulatory noradrenergic afferents to the hypothalamic PVN are decreased during lactation, maintaining stress hyporesponsiveness. We also determined whether PVN noradrenergic afferents could modulate suckling-induced luteinizing hormone (LH) suppression. Virgin and lactating females, on day 2 of lactation, received either sham (SHAM) or 6-hydroxydopamine (6OH-DA) lesions over the PVN. Suppression of plasma LH secretion following a suckling test was determined on day 9 in ovariectomized females and plasma ACTH and corticosterone (B) responses to swim stress were determined on day 11 of lactation. In virgin females, 6OH-DA lesion caused a significant reduction in the ACTH and B responses to swim stress. In SHAM lactating females, plasma ACTH response to stress was blunted compared to SHAM virgins, but 6-OHDA lesion did not reduce ACTH levels further. Lesions in lactating females reduced basal LH secretion, although not significantly, but suckling did not further inhibit LH secretion as observed in SHAM lactating females. In all lesioned groups, PVN tyrosine hydroxylase (TH) immunoreactivity was reduced compared to SHAM rats. These results suggest that brainstem (nor)adrenergic inputs to the PVN act to facilitate ACTH stress response in virgin rats, while in lactating rats this facilitation is absent. In addition, (nor)adrenergic cells projecting to the PVN might also participate in the modulation of GnRH and LH secretion during suckling.