Abe Hideki, Keen Kim L, Terasawa Ei
Wisconsin National Primate Research Center, University of Wisconsin, 1223 Capitol Court, Madison, Wisconsin 53715-1299, USA.
Endocrinology. 2008 Mar;149(3):1155-62. doi: 10.1210/en.2007-0942. Epub 2007 Dec 13.
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+)) 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+) oscillations within a few minutes. E(2) also increased the frequency of Ca(2+) synchronization among LHRH-1 neurons. Similar E(2) effects on the frequency of Ca(2+) 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+) oscillations and synchronizations, indicating that effects estrogens on Ca(2+) 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+) 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.
雌激素在促性腺激素释放激素-1（LHRH-1）神经元中的反馈控制在生殖功能中起关键作用。然而，雌激素在LHRH-1神经元中的作用机制仍不清楚。在本研究中，检测了雌激素对灵长类LHRH-1神经元细胞内钙（[Ca(2+)]i）振荡的影响。应用17β-雌二醇（E(2)，1 nM）10分钟，在几分钟内增加了[Ca(2+)]i振荡的频率。E(2)还增加了LHRH-1神经元之间[Ca(2+)]i同步的频率。在存在河豚毒素的情况下，观察到E(2)对[Ca(2+)]i振荡频率有类似影响，表明雌激素似乎对LHRH-1神经元有直接作用。此外，应用一种不能透过核膜的雌激素树枝状聚合物共轭物而非对照树枝状聚合物，导致[Ca(2+)]i振荡和同步频率显著增加，表明雌激素对[Ca(2+)]i振荡及其同步的影响不需要进入细胞核。在雌激素受体拮抗剂ICI 182,780存在的情况下，细胞暴露于E(2)不会改变E(2)诱导的[Ca(2+)]i振荡频率增加或E(2)诱导的同步频率增加。总体而言，雌激素通过位于灵长类LHRH-1神经元细胞膜/细胞质中的受体诱导快速、直接的刺激作用，且雌激素的这种作用由一种尚未确定的ICI 182,780不敏感机制介导。
