Abstract
Experiments were undertaken to examine the role of ovarian steroids in peripartum programming of oxytocin sensitivity of limbic neurons implicated in oxytocin-induced facilitation of the milk-ejection reflex. In vivo recordings of neurons in the bed nuclei of the stria terminalis and ventrolateral septum of pre-parturient rats which had undergone prior ovariectomy and hysterectomy showed that oestradiol significantly increased the excitatory responses of bed nuclei/ventrolateral septum neurons to intracerebroventricular oxytocin, compared to oil-treated controls. Oestradiol also increased the excitation of bed nuclei neurons to the selective oxytocin agonist, [Thr 4,Gly 7]oxytocin in brain slices from steroid pre-treated ovariectomized hysterectomized rats, so that both the proportion of responsive neurons, and the magnitude of their responses were significantly increased. Parallel autoradiographic studies showed that oxytocin binding in the medial bed nuclei and ventrolateral septum was selectively increased following oestradiol treatment. Progesterone pre-treatment had no effect on either oxytocin sensitivity of bed nuclei/ventrolateral septum neurons recorded in vivo, or on oxytocin binding in the medial bed nuclei and ventrolateral septum, compared to oil-treated controls. Mean responses to [Thr 4,Gly 7]oxytocin in bed nuclei neurons recorded in slices from progesterone-treated rats were larger than controls, but this effect was highly variable. These results demonstrate that oestradiol greatly enhances oxytocin receptor expression and sensitivity of bed nuclei/ventrolateral septum neurons to oxytocin over the peripartum period, consistent with involvement of this steroid in enhancing oxytocin regulation of neuroendocrine and behavioural adaptations required for lactation.
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