[Frontiers in Bioscience 16, 1560-1573, January 1, 2011]

Physiological consequences of membrane-initiated estrogen signaling in the brain

Troy A. Roepke1, Oline K. Ronnekleiv1,2, Martin J. Kelly1,2

1Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239, 2Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006.


1. Abstract
2. Introduction
3. Membrane Estrogen Signaling
4. Membrane E2 Signaling and Reproduction
4.1. Membrane E2 signaling and GnRH secretion
4.2. Membrane E2 signaling and sex behavior
5. Membrane E2 Signaling and Homeostasis
5.1. Membrane E2 signaling and energy balance
5.2. Membrane E2 signaling, thermoregulation and bone remodeling
6. Membrane E2 signaling in the Hippocampus
6.1. Memory & cognition
6.2. Neuroprotection
7. Summary
8. Acknowledgements
9. References


Many of the actions of 17beta-estradiol (E2) in the central nervous system (CNS) are mediated via the classical nuclear steroid receptors, ERalpha and ERbeta, which interact with the estrogen response element to modulate gene expression. In addition to the nuclear-initiated estrogen signaling, E2 signaling in the brain can occur rapidly within minutes prior to any sufficient effects on transcription of relevant genes. These rapid, membrane-initiated E2 signaling mechanisms have now been characterized in many brain regions, most importantly in neurons of the hypothalamus and hippocampus. Furthermore, our understanding of the physiological effects of membrane-initiated pathways is now a major field of interest in the hypothalamic control of reproduction, energy balance, thermoregulation and other homeostatic functions as well as the effects of E2 on physiological and pathophysiological functions of the hippocampus. Membrane signaling pathways impact neuronal excitability, signal transduction, cell death, neurotransmitter release and gene expression. This review will summarize recent findings on membrane-initiated E2 signaling in the hypothalamus and hippocampus and its contribution to the control of physiological and behavioral functions.