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 17estradiol (E₂, 1 nM) for 10 min increased the frequency of [Ca²⁺]_i oscillations within a few minutes. E₂ also increased the frequency of [Ca²⁺]_i synchronization among LHRH-1 neurons. Similar E₂ effects on the frequency of [Ca²⁺]_i oscillations were observed under the presence of TTX, 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 E₂ in the presence of the estrogen receptor (ER) antagonist, ICI 182,780, did not change the E₂-induced increase in the frequency of [Ca²⁺]_i oscillations, nor the E₂-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.