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 ([Ca(2+)](i)) oscillations in primate LHRH-1 neurons was examined. Application of 17beta-estradiol (E(2), 1 nm) for 10 min increased the frequency of [Ca(2+)](i) oscillations within a few minutes. E(2) also increased the frequency of [Ca(2+)](i) synchronization among LHRH-1 neurons. Similar E(2) effects on the frequency of [Ca(2+)](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 [Ca(2+)](i) oscillations and synchronizations, indicating that effects estrogens on [Ca(2+)](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 [Ca(2+)](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.