Rapid action of estradiol in primate GnRH neurons: The role of estrogen receptor alpha and estrogen receptor beta

Estrogens play a pivotal role in the control of female reproductive function. Recent studies using primate GnRH neurons derived from embryonic nasal placode indicate that 17β-estradiol (E2) causes a rapid stimulatory action. E2 (1 nM) stimulates firing activity and intracellular calcium ([Ca2+]i) oscillations of primate GnRH neurons within a few min. E2 also stimulates GnRH release within 10 min. However, the classical estrogen receptors, ERα and ERβ, do not appear to play a role in E2-induced [Ca2+]i oscillations or GnRH release, as the estrogen receptor antagonist, ICI 182,780, failed to block these responses. Rather, this rapid E2 action is, at least in part, mediated by a G-protein coupled receptor GPR30. In the present study we further investigate the role of ERα and ERβ in the rapid action of E2 by knocking down cellular ERα and ERβ by transfection of GnRH neurons with specific siRNA for rhesus monkey ERα and ERβ. Results indicate that cellular knockdown of ERα and ERβ failed to block the E2-induced changes in [Ca2+]i oscillations. It is concluded that neither ERα nor ERβ is required for the rapid action of E2 in primate GnRH neurons.

► Estradiol induces a rapid action in primate GnRH neurons.
► Cellular knockdown of ERα and ERβ do not block the rapid action of estradiol.
► Rather, it appears that this estradiol action is mediated by GPR30.