REDUCED RESPONSE OF THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS TO ALPHA(1)-AGONIST STIMULATION DURING LACTATION

To determine whether altered noradrenergic activation of the hypothala mo-pituitary-adrenal (HPA) axis contributes to the attenuated neuroend ocrine response to stress observed during lactation, the effect of int racerebroventricular injection of the alpha(1)-agonist methoxamine (10 0 mu g) was compared between virgin and lactating rats. Virgin rats sh owed significant increases in plasma corticosterone after methoxamine, reaching 317 +/- 44 ng/ml at 10 min and remaining significantly eleva ted for more than 120 min, but lactating rats showed no significant in crease in corticosterone levels. Furthermore, methoxamine induced an i ncrease in paraventricular nucleus (PVN) CRF messenger RNA expression in virgin, but not lactating, animals. Both groups of rats exhibited c omparable elevations in plasma PRL after methoxamine treatment. Argini ne vasopressin messenger RNA expression within the parvocellular PVN w as greater in the lactating animals than in the virgin controls, but m ethoxamine injection was without further effect. Studies performed on ovariectomized virgin rats and ovariectomized rats receiving estradiol or progesterone replacement failed to reproduce the attenuated HPA re sponses seen after methoxamine treatment, although methoxamine-induced PRL levels were greatly increased by estradiol, probably arising from an effect on hormone synthesis. In vitro electrophysiological recordi ngs of PVN neurons in hypothalamic slices from proestrous virgin and l actating rats showed that 45-52% of neurons in both groups exhibited e xcitatory responses to 10(-4) M methoxamine, but there was a different ial response to 10(-5) M methoxamine, with PVN neurons from lactating animals failing to show a response. These data show a selective down-r egulation of alpha(1)-mediated activation of the HPA axis in lactating animals. This may contribute to the attenuated stress-induced activat ion of the HPA axis during lactation.