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Endocrinology. 2011 Aug;152(8):3182-91. doi: 10.1210/en.2011-0097. Epub 2011 May 31.

STX, a novel nonsteroidal estrogenic compound, induces rapid action in primate GnRH neuronal calcium dynamics and peptide release.

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  • 1Wisconsin National Primate Research Center, University of Wisconsin, 1223 Capitol Court, Madison, Wisconsin 53715-1299, USA.


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+)](i)), 2) the percentage of cells stimulated, and 3) the synchronization frequency of [Ca(2+)](i) oscillations. STX (10-100 nM) also stimulated GnRH release. The effects of STX on both [Ca(2+)](i) 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+)](i) 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+)](i) 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.

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