Neuroprogesterone signals through Src kinase within RP3V neurons to induce the luteinizing hormone surge in female rats

Neural circuits in female rats are exposed to estradiol and sequential progesterone to regulate the luteinizing hormone (LH) surge and thus ovulation. Estradiol induces progesterone receptors (PGRs) in rostral periventricular region of the third ventricle (RP3V) kisspeptin neurons, and positive feedback estradiol concentrations induce neuroprogesterone (neuroP) synthesis in hypothalamic astrocytes that signal to PGRs expressed in kisspeptin neurons to trigger the LH surge. We tested the hypothesis that neuroP-PGR signals through Src family kinase (Src) to trigger the LH surge. As in vitro, PGR and Src are co-expressed in RP3V neurons. Estradiol treatment increased the number of PGR immunopositive cells and PGR and Src colocalization. Infusion of the Src inhibitor (PP2) into the RP3V, attenuated the LH surge measured by ELISA in trunk blood collected 53 hours post-EB injection. While PP2 reduced the LH surge in 50 g EB treated ovariectomized/adrenalectomized (ovx/adx) rats, activation of either PGR or Src in 2g EB primed animals significantly elevated LH concentrations compared with DMSO treated ovx/adx rats. These results support the importance of Src in the estradiol and neuroP triggering of the LH surge.