Apelin-13 induces lordosis behavior in estradiol-primed ovariectomized rats via the activation of multiple protein kinases in the ventromedial hypothalamus.

The present study aimed to determine whether apelin-13 facilitates lordosis behavior through the activation of specific hypothalamic kinases and to identify which signaling pathways mediate this response. Because lordosis is a well-established neuroendocrine indicator of female sexual receptivity, it served as an appropriate behavioral model to detect peptide-induced facilitation. Thus, we examined the role of protein kinase A (PKA), protein kinase C (PKC), mitogen activated protein kinase (MAPK), or Src kinase (Src), in the facilitation of lordosis behavior following bilateral intrahypothalamic injection of 0.75 μg of apelin-13 to ovariectomized-estradiol benzoate (OVX-EB) primed rats. Apelin-13 consistently induced lordosis at 30, 120, and 240 minutes post-infusion. To explore the role of these kinases, various inhibitors or their vehicles were administered bilaterally into the ventromedial hypothalamus (VMH) of OVX-EB-primed rats 30 min before the infusion of apelin-13. The inhibitors used were Rp-cAMPS for PKA, bisindolilmaleimide (BIS) for PKC, PD98059 for MAPK, and PP2 for Src. The VMH injection of Rp-cAMPS failed to reverse the facilitation of lordosis at the different times tested, while BIS or PP2 decreased the lordosis quotient (LQ) significantly only at 240 min without any statistical effect on the lordosis score (LS). However, PD98059 significantly reduced both the LQ and LS at 120 and 240 min. These data indicate that apelin-13 exerts its facilitatory effects on lordosis through MAPK, PKC, and/or Src, but not PKA pathways.