Apelin-13 elicits lordosis behavior in female rats through the oxytocin/prostaglandin E2/GnRH signaling system.

The present study investigated the role of the oxytocin (OT)/prostaglandin E2 (PGE2)/gonadotropin-releasing hormone (GnRH) and the progesterone receptor (PR) pathways in facilitating lordosis behavior induced by intrahypothalamic administration of 0.75 μg of apelin-13 in ovariectomized (OVX) rats primed with estradiol benzoate (EB). To explore this pathway, various inhibitors were administered bilaterally into the ventromedial hypothalamus (VMH) of EB-primed rats 30 min before the infusion of apelin-13. The inhibitors used included atosiban (ATO), an OT receptor antagonist; acetylsalicylic acid (aspirin), a cyclooxygenase-2 (COX-2) inhibitor; ONOAE3-208 (ONO), a PGE2 receptor antagonist; RU486, an antiprogestin for the PR; and antide, a GnRH-1 receptor antagonist. Apelin-13 at this dosage used, consistently induced lordosis at 30, 120, and 240 min post-infusion. The administration of atosiban, ONO, antide, and RU486, significantly reduced both the lordosis quotient (LQ) and lordosis reflex score (LS) at all assessed time points. In contrast, aspirin only decreased the LQ at 30 and 120 min, while the LS was reduced at all times tested. Because the OT/PGE2/GnRH pathway has been widely demonstrated in hypothalamic astrocytes as a regulator of GnRH release, it may also play a role in regulating female sexual behavior in estradiol-pretreated rats.