Membrane estradiol signaling in the brain

Abstract

While the physiology of membrane-initiated estradiol signaling in the nervous system has remained elusive, a great deal of progress has been made toward understanding the activation of cell signaling. Membrane-initiated estradiol signaling activates G proteins and their downstream cascades, but the identity of membrane receptors and the proximal signaling mechanism(s) have been more difficult to elucidate. Mounting evidence suggests that classical intracellular estrogen receptor-α (ERα) and ERβ are trafficked to the membrane to mediate estradiol cell signaling. Moreover, an interaction of membrane ERα and ERβ with metabotropic glutamate receptors has been identified that explains the pleomorphic actions of membrane-initiated estradiol signaling. This review focuses on the mechanism of actions initiated by membrane estradiol receptors and discusses the role of scaffold proteins and signaling cascades involved in the regulation of nociception, sexual receptivity and the synthesis of neuroprogesterone, an important component in the central nervous system signaling.

Estrogenic influences in pain processing

“…This enables the activation of non-genomic responses regionally, thereby avoiding the need for high estrogen concentrations systemically, concentrations that could cause severe adverse effects on non-neural tissue (Cornil et al, 2006). The regulation of lordosis behavior (Micevych and Mermelstein, 2008) and signaling in the dorsal root ganglion (Chaban and Micevych, 2005) are in the time range more compatible with non-classic mechanisms (Micevych and Dominguez, 2009).…”

Estrous behavior in dairy cows: identification of underlying mechanisms and gene functions

“…As E2, through its effects on GnRH and LH, also regulates the LH surge and ovulation, E2 indirectly synchronizes mating and ovulation. The lordosis reflex has been used as a behavioral model to study the functioning of serotonin (Uphouse, 2000;Uphouse et al, 2007) and E2 signaling (Micevych and Dominguez, 2009;. Although these studies do not aim directly to unravel the regulation of estrous behavior, they support the findings of Pfaff and coworkers that E2 induces estrous behavior via ER gene expression and membrane signaling.…”

“…Apart from genomic (classical ER) signaling, the estrogenic control of estrous behavior also involves membrane signaling mechanisms via secondary messengers like phosphoinositide 3 kinase, cAMP response element binding proteins and extracellular signal regulated kinases ERa 5 estrogen receptor-a; ERb 5 estrogen receptor-b; E2 5 estradiol; P4 5 progesterone; GnRH 5 gonadotropin releasing hormone; GnRH-R 5 gonadotropin releasing hormone receptor; PI3K 5 phosphoinositide 3 kinase; IGF-1 5 insulin-like growth factor-1; LH 5 luteinizing hormone. (Mendez et al, 2006;Kelly and Rønnekleiv, 2009;Micevych and Dominguez, 2009). …”

Mapping the effects of vitamin D in multiple sclerosis

“…Besides the classical cytosolic receptors, the earlier mentioned membrane-located variants are also likely to be relevant. Estradiol and progesterone binding was still observed in the CNS of ER and PR knock-out mice [296,300] . These membrane receptors may be G-proteincoupled receptors [296,[300][301] .…”

“…Estradiol and progesterone binding was still observed in the CNS of ER and PR knock-out mice [296,300] . These membrane receptors may be G-proteincoupled receptors [296,[300][301] . At least those for estrogen have been found in neurons and astrocytes [302] , and those for progesterone have been found on neurons and the several glia cells in mice [303] .…”