Activity‐dependent modulation of GnRH neuron activity by acute estradiol

Abstract

Estradiol (E2) exerts potent feedback actions upon gonadotropin‐releasing hormone (GnRH) neurons and part of this feedback action may occur through rapid E2 actions. Using a transgenic GnRH‐Pericam mouse line that allows real‐time intracellular calcium concentrations ([Ca²⁺]i) to be monitored in adult GnRH neurons in the brain slice preparation, we have examined the acute effects of 100pM‐100nM E2 on [Ca²⁺]i transients in spontaneously active GnRH neurons. Approximately 30% of GnRH neurons exhibit spontaneous [Ca²⁺]i transients at a frequency greater than two transients/15 min in adult female mice. In these cells, treatment with an incremental 1, 10, 100nM E2 protocol or 100pM E2 alone resulted in the suppression or complete cessation of [Ca²⁺]i transients in 15 of 18 (83%) GnRH neurons. This effect was mimicked by E2 bound to albumin suggesting a membrane site of action, and was maintained in estrogen receptor beta knockout mice indicating that this receptor is not essential for the rapid suppression of [Ca²⁺]i transients. These findings contrast with those GnRH neurons exhibiting very few or no [Ca²⁺]i transients (<2 transients/15min) that exhibit the opposite response of being activated by acute E2. A series of dual calcium‐cell‐attached electrical recordings showed that [Ca²⁺]i transients were associated with GnRH neuron burst firing and that E2 suppression or activation of [Ca²⁺]i transients was mirrored by a depression or initiation of burst firing. Together, these studies demonstrate that the acute actions of E2 on GnRH neurons are critically dependent upon the state of bursting electrical activity of the cell.

© 2012 The Authors. Journal of Neuroendocrinology © 2012 Blackwell Publishing Ltd