Systemic oxytocin induces a prolactin secretory rhythm via the pelvic nerve in ovariectomized rats

Abstract

We have shown previously that an intravenous injection of oxytocin (OT) in ovariectomized (OVX) rats initiates a circadian rhythm of prolactin (PRL) secretion similar to that observed after cervical stimulation (CS). In this study, we investigated the pathway through which OT triggers the PRL rhythm. We first tested whether an intracerebroventricular injection of OT could trigger the PRL secretory rhythm. As it did not, we injected OT intravenously while an OT receptor antagonist was infused intravenously. This antagonist completely abolished the PRL surges, suggesting that a peripheral target of OT is necessary for triggering the PRL rhythm. We hypothesized that OT may induce PRL release, which would be transported into the brain and trigger the rhythm. In agreement with this, OT injection increased circulating PRL by 5 min. To test whether this acute increase in PRL release would induce the PRL rhythm, we compared the effect of intravenously administered thyrotropin-releasing hormone (TRH) and OT. Although TRH injection also increased PRL to a comparable level after 5 min, only OT-injected animals expressed the PRL secretory rhythm. Motivated by prior findings that bilateral resection of the pelvic nerve blocks CS-induced pseudopregnancy and OT-induced facilitation of lordosis, we then hypothesized that the OT signal may be transmitted through the pelvic nerve. In fact, OT injection failed to induce a PRL secretory rhythm in pelvic-neurectomized animals, suggesting that the integrity of the pelvic nerve is necessary for the systemic OT induction of the PRL secretory rhythm in OVX rats.

Fig. 1.

Central (intracerebroventricular) vs. peripheral (intravenous) effect of oxytocin (OT) to induce the prolactin (PRL) secretory rhythm. A: ovariectomized (OVX) rats were injected with OT (0.3 μg, n = 12) or vehicle (n = 7) intracerebroventricularly at 1600 of day 0 (arrow). B: OVX rats were injected intravenously with OT (5 μg) at 1600 of day 0 (arrow). In 13 rats, the OT antagonist (OTa, 9 μg/h) was infused intravenously beginning around 1200 of day 0 for 24 h. Blood samples were withdrawn during the next 2 days to observe the PRL diurnal and nocturnal surges. Data are presented as means ± SE. #P < 0.05 and ###P < 0.001 vs. control group at the same time. *P < 0.05, ***P < 0.001 vs. 0100 of day 2 PRL in the same experimental group.

Fig. 2.

Correlation between immediate PRL release and the PRL secretory rhythm. A: OVX rats were injected with saline (n = 8) or OT (n = 9) iv at 1600 of day 0 (arrow). Blood samples were taken immediately before and 5 and 10 min following peripheral injection and, thereafter, during the next 2 days to observe the PRL diurnal and nocturnal surges. B: same experimental design was repeated injecting rats with saline (n = 8) or TRH (n = 9). Data are presented as means ± SE. #P < 0.05 and ##P < 0.01 vs. control group at the same time. *P < 0.05 vs. 1600 PRL in the same experimental group.

Fig. 3.

The effect of pelvic neurectomy on the OT-induced PRL secretory rhythm. A: photograph showing the location of the pelvic nerve in a perfused rat. B: comparison between bladders from two sham-operated animals (left) and one from a pelvic neurectomized animal (right). C: OVX rats had their pelvic nerve cut bilaterally (PEX; n = 9) or were submitted to sham surgery (Sham; n =12). After recovery, they were injected with OT intravenously at 1600 of day 0 (arrow). Blood samples were withdrawn immediately after the injection and during the next 2 days to observe the PRL diurnal and nocturnal surges. Data are presented as means ± SE. #P < 0.05 ##P < 0.01, and ###P < 0.001 vs. sham group at the same time. *P < 0.05 and ***P < 0.001 vs. 1600 PRL in the same experimental group.