Research ReportA selective membrane estrogen receptor agonist maintains autonomic functions in hypoestrogenic states
Section snippets
Membrane-initiated signaling of estrogens
It has been known for a number of years that 17β-estradiol (E2) has acute, membrane-initiated signaling actions in the brain (Kelly and Rønnekleiv, 2002, Rønnekleiv and Kelly, 2005, Micevych and Dominguez, 2009). A decade ago the nature and physiological significance of these actions were a matter of debate, but it is now widely accepted that some of the actions of E2 are quite rapid and cannot be attributed to the classical nuclear-initiated steroid signaling of ERα or ERβ. Importantly, ERα
Membrane-initiated signaling of E2 and hypothalamic control of autonomic functions
Besides its quintessential role in the feedback control of the reproductive axis, E2 modulates a number of hypothalamic-regulated autonomic functions, most notably energy homeostasis and temperature. E2 signaling via ERα is a critical component in the hypothalamic regulation of energy balance (Geary et al., 2001). In rodents, hypo-estrogenic states are clearly associated with decreased activity and an increase in body weight (Czaja and Goy, 1975, Butera and Czaja, 1984, Czaja, 1984, McCaffrey
Summary
It is obvious from the plethora of studies using membrane-delimited E2 ligands and the mER selective ligand STX that “genomic” actions of E2 in the brain do not require the direct nuclear targeting of estrogen receptors (ERα and ERβ). Signals that are initiated by E2 at the plasma membrane can trigger multiple intracellular signaling cascades including activation of MAPK, PI3K, and PKC pathways (Watters et al., 1997, Bi et al., 2001, Cato et al., 2002, Yang et al., 2003, Deisseroth et al., 2003
Acknowledgments
The authors thank current and former members of their laboratories who contributed to the work described herein, especially Drs. Jian Qiu, Troy A. Roepke and Chunguang Zhang and Ms. Martha A. Bosch. Research reported in this publication was supported by the National Institutes Health Grants NS 38809, NS 43330 and DK 68098. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health.
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