Reduced Response of the Hypothalamo-Pituitary-Adrenal Axis to  1-Agonist Stimulation during Lactation

Abstract

To determine whether altered noradrenergic activation of the hypothalamo-pituitary-adrenal (HPA) axis contributes to the attenuated neuroendocrine response to stress observed during lactation, the effect of intracerebroventricular injection of the alpha1-agonist methoxamine (100 microg) was compared between virgin and lactating rats. Virgin rats showed significant increases in plasma corticosterone after methoxamine, reaching 317 +/- 44 ng/ml at 10 min and remaining significantly elevated for more than 120 min, but lactating rats showed no significant increase in corticosterone levels. Furthermore, methoxamine induced an increase in paraventricular nucleus (PVN) CRF messenger RNA expression in virgin, but not lactating, animals. Both groups of rats exhibited comparable elevations in plasma PRL after methoxamine treatment. Arginine vasopressin messenger RNA expression within the parvocellular PVN was greater in the lactating animals than in the virgin controls, but methoxamine 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 responses 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 recordings of PVN neurons in hypothalamic slices from proestrous virgin and lactating rats showed that 45-52% of neurons in both groups exhibited excitatory responses to 10(-4) M methoxamine, but there was a differential response to 10(-5) M methoxamine, with PVN neurons from lactating animals failing to show a response. These data show a selective down-regulation of alpha1-mediated activation of the HPA axis in lactating animals. This may contribute to the attenuated stress-induced activation of the HPA axis during lactation.

Blunted HPA axis response in lactating, vasopressin-deficient Brattleboro rats

“…During lactation, the exposure of mothers to different acute stressful stimuli results in a blunted response of the HPA axis when compared with that in virgin rats (Walker et al 1992, Windle et al 1997, Brunton et al 2008. In lactating women, ACTH and cortisol responses to treadmill exercise have been found to be lower within the first 2 h of suckling but not subsequently (Altemus et al 1995).…”

Differential Responses of Thyrotropin-Releasing Hormone (TRH) Neurons to Cold Exposure or Suckling Indicate Functional Heterogeneity of the TRH System in the Paraventricular Nucleus of the Rat Hypothalamus

“…The hyporesponse to stressors observed in lactating dams has been suggested to be due to modifications in neuronal activity induced by pups suckling and not to changes in the sensitivity to glucocorticoid-negative feedback [40]. Glucocorticoids are important modulators of catecholaminergic cells in brainstem and diminish the stress-induced release of norepinephrine in the PVN [41], but the response to α 1 -adrenergic receptor activation is also reduced in corticotropin release hormone-PVN neurons of the lactating dam [42]. The difference observed in corticosterone levels in the two groups of lactating rats (with or without pups removal for 8 h) supports the attenuating effect to stress that pups confer to their mothers [40].…”

Social modulation of stress responses

“…Inhibition of the HPA axis by glucocorticoids and oxytocin. cerebroventricular injection of a noradrenergic agonist [85] results in the expected induction of CRF mRNA in the paraventricular nucleus of lactating rats. Furthermore, ACTH response to administration of exogenous CRF is reduced in lactating rats compared to nulliparous controls [79].…”