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 µg EB treated ovariectomized/adrenalectomized (ovx/adx) rats, activation of either PGR or Src in 2µg 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.
Progesterone synthesis and signaling in the hypothalamus are critical events for the luteinizing hormone (LH) surge that induces ovulation and are associated with "estrogen positive feedback" in the rodent. [1][2][3][4][5][6][7][8][9][10][11] Ovulation is coordinated with reproductive behavior and development of the uterine lining to maximize the likelihood that copulation results in fertilization and pregnancy. In mammals, these events are orchestrated by hormones of the hypothalamicpituitary-ovarian axis.Circulating concentrations of ovarian estradiol slowly rise during diestrus I and II. This initial rise of estradiol exerts negative feedback on the hypothalamus and pituitary but ultimately initiates the activation of a complex interplay of astrocyte and neuronal circuitry,
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