Oxytocin Action at the Lactotroph Is Required for Prolactin Surges in Cervically Stimulated Ovariectomized Rats

Abstract

Cervical stimulation induces two daily rhythmic prolactin surges, nocturnal and diurnal, which persist for several days. We have shown that a bolus injection of oxytocin initiates a similar prolactin rhythm, which persists despite low levels of oxytocin after injection. This suggests that oxytocin may trigger the cervical stimulation-induced rhythmic prolactin surges. To investigate this hypothesis, we infused an oxytocin antagonist that does not cross the blood-brain barrier for 24 h before and after cervical stimulation and measured serum prolactin. We also measured dopaminergic neuronal activity because mathematical modeling predicted that this activity would be low in the presence of the oxytocin antagonist. We thus tested this hypothesis by measuring dopaminergic neuronal activity in the tuberoinfundibular, periventricular hypophyseal, and tuberohypophyseal dopaminergic neurons. Infusion of oxytocin antagonist before cervical stimulation abolished prolactin surges, and infusion of oxytocin antagonist after cervical stimulation abolished the diurnal and significantly decreased the nocturnal surges of prolactin. The rhythmic prolactin surges returned after the clearance of the oxytocin antagonist. Hypothalamic dopaminergic activity was elevated in antiphase with prolactin surges, and the antiphase elevation was abolished by the oxytocin antagonist in the tuberoinfundibular and tuberohypophyseal dopaminergic neurons, consistent with the mathematical model. These findings suggest that oxytocin is a physiologically relevant prolactin-releasing factor. However, the cervical stimulation-induced prolactin surges are maintained even in the absence of oxytocin actions at the lactotroph, which strongly suggests the maintenance of prolactin surges are not dependent upon oxytocin actions at the pituitary gland.