Wisconsin National Primate Research Center, University of Wisconsin, 1223 Capitol Court, Madison, Wisconsin 53715-1299, USA.
Endocrinology. 2011 Aug;152(8):3182-91. doi: 10.1210/en.2011-0097. Epub 2011 May 31.
Previously, we reported that 1 nM 17ß-estradiol (E(2)) induces a rapid action, which is, in part, mediated through the G protein-coupled receptor GPR30 in primate GnRH neurons. Because it has been reported that the diphenylacrylamide compound, STX, causes estrogenic action in the mouse and guinea pig hypothalamus, the present study examined effects of STX in primate GnRH neurons and whether there is an action independent of GPR30. Results are summarized as follows. STX (10 nM) exposure increased 1) the oscillation frequency of intracellular calcium concentration (Ca(2+)), 2) the percentage of cells stimulated, and 3) the synchronization frequency of Ca(2+) oscillations. STX (10-100 nM) also stimulated GnRH release. The effects of STX on both Ca(2+) oscillations and GnRH release were similar to those caused by E(2) (1 nM), although with less magnitude. STX (10 nM)-induced changes in Ca(2+) oscillations were not altered by GPR30 small interfering RNA transfection, indicating that STX-sensitive receptors differ from GPR30. Finally, a higher dose of E(2) (10 nM) induced a larger change in Ca(2+) oscillations than that with a smaller dose of E(2) (1 nM), and the effects of 10 nM E(2) were reduced but not completely blocked by GPR30 small interfering RNA transfection, indicating that the effects of 10 nM E(2) in primate GnRH neurons are mediated by multiple membrane receptors, including GPR30 and STX-sensitive receptors. Collectively, the rapid action of E(2) mediated through GPR30 differs from that mediated through STX-sensitive receptors. The molecular structure of the STX-sensitive receptor remains to be identified.
先前，我们报道过 1 nM 17ß-雌二醇（E2）诱导一种快速作用，部分是通过灵长类 GnRH 神经元中的 G 蛋白偶联受体 GPR30 介导的。由于已经报道过二苯丙烯酰胺化合物 STX 在小鼠和豚鼠下丘脑引起雌激素作用，本研究检查了 STX 在灵长类 GnRH 神经元中的作用，以及是否存在独立于 GPR30 的作用。结果总结如下。STX（10 nM）暴露增加了 1）细胞内钙离子浓度 ([Ca2+]（i））的振荡频率，2）受刺激细胞的百分比，和 3）[Ca2+]（i）振荡的同步频率。STX（10-100 nM）也刺激 GnRH 释放。STX 对 [Ca2+]（i）振荡和 GnRH 释放的作用与 1 nM 的 E2 相似，尽管幅度较小。STX（10 nM）诱导的 [Ca2+]（i）振荡变化不受 GPR30 小干扰 RNA 转染的影响，表明 STX 敏感受体与 GPR30 不同。最后，较高剂量的 E2（10 nM）诱导的 [Ca2+]（i）振荡变化大于较小剂量的 E2（1 nM），并且 10 nM E2 的作用被 GPR30 小干扰 RNA 转染部分降低但未完全阻断，表明 10 nM E2 在灵长类 GnRH 神经元中的作用是通过多种膜受体介导的，包括 GPR30 和 STX 敏感受体。总之，E2 通过 GPR30 介导的快速作用与通过 STX 敏感受体介导的作用不同。STX 敏感受体的分子结构仍有待确定。
