F1000Prime Recommendation of [Romanò N and Herbison AE, J Neuroendocrinol 2012]

It is known that ovarian estradiol is a key factor in the activity of gonadotropin-releasing hormone (GnRH)-secreting neurons, and consequently of the whole reproductive functions, by exerting feedback regulations, mainly through the interaction with classical intracellular receptors (estrogen receptors [ERs]). Some aspects of these regulations are still without a clear explanation. Using elegant real-time intracellular calcium imaging analysis and transgenic animal models, the authors of this study provide the demonstration that the application of picomolar estradiol on hypothalamic slice preparations induces the suppression of calcium transients in a subpopulation of GnRH neurons that spontaneously exhibit these transients at high frequency. On the contrary, the GnRH neurons that exhibited few or no transients were either insensitive to or activated by estradiol application. The hypothesis proposed by the authors includes a regulatory action of estradiol that, by the inhibition of high frequency GnRH neurons and the activation of low frequency ones, might moderate most GnRH neurons firing at similar levels. In conclusion, this experimental work provides the evidence that the spontaneous activity of GnRH neurons determines their response to acute estradiol exposure; this fine-tuning of estradiol may coordinate the activity levels of a large population of such neurons and contribute to estrogen-induced negative feedback on GnRH, and therefore gonadotropin, secretion.