Role of Oxytocin in Prolactin Secretion during Late Pregnancy

During late pregnancy, the blockade of progesterone action by mifepristone (Mp) treatment induces a dopaminergic tone fall that enables naloxone (NAL) administration to release pituitary prolactin (PRL). We determined whether oxytocin (OT), which stimulates PRL secretion acting directly on anterior pituitary lactotrophs, mediates the stimulatory action of Mp and NAL on PRL secretion during late pregnancy.

On day 19 of pregnancy, circulating and pituitary OT and PRL levels were measured by radioimmunoassay, 10, 20, and 30 min after NAL (given at 17:30 h) in rats pretreated with Mp (at 08:00 h). Pituitary OT receptor (OTR) expression in Mp-treated rats was evaluated by RT-PCR. Activation of OT neurons in Mp-NAL-treated rats was measured counting double immunoreactive neurons for Fos and OT (Fos-OT-ir) in supraoptic nuclei (SON), and medial (PaMM) and lateral magnocellular divisions of paraventricular nuclei.

Elevated serum OT and decreased pituitary OT were observed 10 min after NAL administration in both vehicle- and Mp-treated rats. This PRL increase was prevented by previous i.p. administration of an OTR antagonist, but intracerebroventricular OT administration was ineffective. Mp increased pituitary OTR expression at 18:00 h. Only Mp-NAL increased Fos-OT-ir neurons in the PaMM and SON.

These findings suggest that PRL secretion induced by Mp-NAL treatment is preceded by OT release. These results, together with the activation of hypothalamic OT neurons and the higher expression of pituitary OTR, support the hypothesis that, during late pregnancy, OT may act at the pituitary level to facilitate PRL secretion if the inhibitory action of progesterone is blocked.