Estrogen Receptor-β in the Gonadotropin-Releasing Hormone Neuron

Estrogen regulation of gonadotropin-releasing hormone (GnRH) neuronal activity plays a crucial role in homeostatic regulation of the hypothalamic-pituitary-gonadal axis. Estrogen also coordinates a complex series of physiological changes culminating with a surge of gonadotropin secretion that triggers ovulation of a developed follicle from the ovary. The coordinated functions of estrogen ensure that the female will elaborate appropriate reproductive behaviors ultimately designed to deliver sperm to the oocyte and to provide a receptive uterine environment for the fertilized embryo. Although the effects of estrogen on GnRH neuronal function have long been proposed to be indirect due to the presumed lack of estrogen receptors in GnRH neurons, the identification of alternative estrogen signaling pathways, including estrogen receptor (ER)beta and membrane ERs such as GPR30, has put the focus back on estrogen's effect at the level of the GnRH neuron itself. One candidate to mediate the effects of estrogen is the beta isoform of the estrogen receptor. We review the evidence for a role for ER beta-mediated regulation of GnRH neuronal function.