Estradiol signaling in the regulation of reproduction and energy balance

Our knowledge of membrane estrogenic signaling mechanisms and their interactions that regulate physiology and behavior has grown rapidly over the past three decades. The discovery of novel membrane estrogen receptors and their signaling mechanisms has started to reveal the complex timing and interactions of these various signaling mechanisms with classical genomic steroid actions within the nervous system to regulate physiology and behavior. The activation of the various estrogenic signaling mechanisms is site specific and differs across the estrous cycle acting through both classical genomic mechanisms and rapid membrane-initiated signaling to coordinate reproductive behavior and physiology. This review focuses on our current understanding of estrogenic signaling mechanisms to promote: (1) sexual receptivity within the arcuate nucleus of the hypothalamus, (2) estrogen positive feedback that stimulates de novo neuroprogesterone synthesis to trigger the luteinizing hormone surge important for ovulation and estrous cyclicity, and (3) alterations in energy balance.

► A general background on membrane estrogen receptors (mERs) is provided.
► mER activation of metabotropic glutamate receptor-1a (mER-mGluR1a) in reproduction.
► mER-mGluR1a signaling is important for estradiol facilitation of sexual behavior.
► mER-mGluR1a signaling is important for neuroprogesterone synthesis and LH surge.
► Estradiol signaling mechanisms that regulate energy homeostasis are reviewed.