Rapid action of estrogens on intracellular calcium oscillations in primate luteinizing hormone-releasing hormone-1 neurons

Feedback controls of estrogen in LHRH-1 neurons play a pivotal role in reproductive function. However, the mechanism of estrogen action in LHRH-1 neurons is still unclear. In the present study, the effect of estrogens on intracellular calcium ([Ca2+](i)) oscillations in primate LHRH-1 neurons was examined. Application of 17 beta-estradiol (E-2, 1 nm) for 10 min increased the frequency of [Ca2+](i) oscillations within a few minutes. E-2 also increased the frequency of [Ca2+](i) synchronization among LHRH-1 neurons. Similar E-2 effects on the frequency of [Ca2+](i) oscillations were observed under the presence of tetrodotoxin, indicating that estrogen appears to cause direct action on LHRH-1 neurons. Moreover, application of a nuclear membrane-impermeable estrogen dendrimer conjugate, not control dendrimer, resulted in a robust increase in the frequencies of [Ca2+](i) oscillations and synchronizations, indicating that effects estrogens on [Ca2+](i) oscillations and their synchronizations do not require their entry into the cell nucleus. Exposure of cells to E-2 in the presence of the estrogen receptor antagonist ICI 182,780 did not change the E-2-induced increase in the frequency of [Ca2+](i) oscillations or the E-2-induced increase in the synchronization frequency. Collectively, estrogens induce rapid, direct stimulatory actions through receptors located in the cell membrane/cytoplasm of primate LHRH-1 neurons, and this action of estrogens is mediated by an ICI 182,780-insensitive mechanism yet to be identified.