Nonclassical Estrogen Modulation of Presynaptic GABA Terminals Modulates Calcium Dynamics in Gonadotropin-Releasing Hormone Neurons

There is increasing recognition that estrogen exerts multifaceted regulatory effects on GnRH neurons. The acute effects of estrogen on calcium dynamics in these cells were examined using a transgenic mouse line that allows real-time measurement of intracellular calcium concentration ([Ca(2+)](i)) inGnRH neurons in the acute brain slice preparation. 17-beta-Estradiol (E2) at 100 pM-100 nM was found to activate [Ca(2+)](i) transients in approximately 40% of GnRH neurons with an approximate 15-min latency. This effect was not replicated by E2-BSA, which limits E2 action to the membrane, 17-alpha-estradiol, the inactive isomer at classical estrogen receptors (ERs), or G-1 the GPR30 agonist. E2 continued to activate [Ca(2+)](i) transients when transcription was blocked. An ER alpha-selective agonist was equally potent in activating [Ca(2+)](i) transients, and E2 remained effective in ER beta knockout X GnRH-Pericam mice.