Kisspeptin stimulates progesterone secretion via the Erk1/2 mitogen-activated protein kinase signaling pathway in rat luteal cells

Objective To observe the effect of kisspeptin on the endocrine function of rat luteal cells. Design Experimental animal study. Setting Research institute laboratory. Animal(s) Immature Sprague-Dawley rats. Intervention(s) The expression of kisspeptin and its receptor, GPR54, in immature rat ovaries treated with gonadotropin was observed via immunohistochemistry and real-time polymerase chain reaction. Then recombinant kisspeptin was used to examine the effect on the endocrine function of rat luteal cells. Main Outcome Measure(s) Expression and localization of kisspeptin, localization of GPR54, P and E 2 secretion, expression of steroidogenic enzymes, and phosphorylation of Erk1/2. Result(s) Real-time polymerase chain reaction indicated that ovarian KiSS-1 mRNA levels increased significantly, showing a peak at the luteal period in gonadotropin-primed immature rats. Immunostaining analysis showed that after gonadotropin treatment, kisspeptin was strongly localized in theca cells, the interstitial compartment, and the corpus luteum and that GPR54 protein was clearly detected in the corpus luteum of rat ovaries. In cultured luteal cells, kisspeptin treatment augmented basal and hCG-induced P levels but not E 2 production, with concomitant increases detected in the transcript levels of key steroidogenic enzymes (StAR, CYP11A, and 3β-HSD). Furthermore, treatment with kisspeptin increased the phosphorylation of Erk1/2 mitogen-activated protein kinase in cultured luteal cells. Conclusion(s) The kisspeptin/GPR54 signaling system could stimulate P secretion in rat luteal cells via the Erk1/2 mitogen-activated protein kinase signaling pathway, suggesting an important role for the function of the corpus luteum.