TY - JOUR
T1 - STX, a novel nonsteroidal estrogenic compound, induces rapid action in primate GnRH neuronal calcium dynamics and peptide release
AU - Kenealy, B. P.
AU - Keen, K. L.
AU - Rønnekleiv, O. K.
AU - Terasawa, Ei
PY - 2011/8
Y1 - 2011/8
N2 - Previously, we reported that 1 nM 17β-estradiol (E2) 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 [Ca2+]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 E2 (1 nM), although with less magnitude. STX (10 nM)-induced changes in [Ca2+]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 [Ca2+]i oscillations than that with a smaller dose of E2 (1 nM), and the effects of 10 nM E2 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 E2 mediated through GPR30 differs from that mediated through STX-sensitive receptors. The molecular structure of the STX-sensitive receptor remains to be identified.
AB - Previously, we reported that 1 nM 17β-estradiol (E2) 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 [Ca2+]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 E2 (1 nM), although with less magnitude. STX (10 nM)-induced changes in [Ca2+]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 [Ca2+]i oscillations than that with a smaller dose of E2 (1 nM), and the effects of 10 nM E2 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 E2 mediated through GPR30 differs from that mediated through STX-sensitive receptors. The molecular structure of the STX-sensitive receptor remains to be identified.
UR - http://www.scopus.com/inward/record.url?scp=79960735392&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960735392&partnerID=8YFLogxK
U2 - 10.1210/en.2011-0097
DO - 10.1210/en.2011-0097
M3 - Article
C2 - 21628385
AN - SCOPUS:79960735392
SN - 0013-7227
VL - 152
SP - 3182
EP - 3191
JO - Endocrinology
JF - Endocrinology
IS - 8
ER -