ReviewMembrane-initiated estrogen signaling in hypothalamic neurons
Section snippets
Nuclear-initiated signaling of E2
Estrogen receptors regulate cellular function through at least two signaling pathways previously broadly classified as “genomic” versus “nongenomic” (McEwen and Alves, 1999, Björnström and Sjöberg, 2005). However, recently the FASEB steroid signaling work group suggested that “membrane-initiated steroid signaling” and “nuclear-initiated steroid signaling” are more appropriate terminologies (Hammes and Levin, 2007). The nuclear-initiated signaling of estrogen via ERα and ERβ exert diverse
Membrane-initiated signaling of E2
It has been known for a number of years that estrogen has acute, membrane-initiated signaling actions in the brain (for review see Kelly and Rønnekleiv, 2002, Rønnekleiv and Kelly, 2005, Bryant et al., 2006). The nature and significance of these actions have been a matter of dispute. However, it is now widely accepted that some of the actions of estrogen are quite rapid and cannot be attributed to the classical nuclear-initiated steroid signaling of ERα or ERβ. One view is that both nuclear and
17β-Estradiol, growth factors and reproduction
Systemic administration of E2 in ovariectomized rats activates IGF-I receptors and induces the association between IGF-I receptors and ERα in the hypothalamus (Quesada and Etgen, 2001, Cardona-Gómez et al., 2002, Mendez et al., 2003). Similar to the effects in cortical neurons, there is an interaction (complex formation) between the p85 subunit of PI3K and ERα within 1–3 h, which leads to activation of Akt (Cardona-Gómez et al., 2002, Mendez et al., 2003). Also, the E2-induced activation of
17β-Estradiol and GnRH neurosecretion
Despite having been studied extensively for over 25 years, the mechanism(s) by which estrogen regulates gonadotropin releasing hormone (GnRH) neurons is not well understood. It has been obvious for a number of years that GnRH neurons are modulated by estrogen in a complex manner. For example, loss of estrogen by ovariectomy disrupts GnRH regulation of pituitary LH secretion and results in elevated levels of plasma LH. This effect is due to the loss of negative feedback actions of E2. However,
Effects of 17β-estradiol on VMH and arcuate neurons: role in regulation of feeding
In addition to its role in the control of reproduction, estrogen is involved in the regulation of appetite, energy expenditure, body weight, adipose tissue deposition and distribution in females (Milewicz et al., 2000, Geary, 2001, Poehlman, 2002). Ovariectomy induces an increase in food intake and decreases ambulatory and wheel running activities in rodents, all of which are reversed with estrogen replacement (Ahdieh and Wade, 1982, Colvin and Sawyer, 1969, Shimomura et al., 1990, Asarian and
Cross-talk between membrane actions and genome activation
The gonadal steroid E2 participates in numerous functions including reproduction, feeding, neuroprotection and cognition. It has been known for some time that the main actions of E2 is to regulate gene transcription through binding to and activating nuclear receptors that can stimulate or inhibit gene transcription at specific DNA binding sites. However, recently it has become clear that E2 can exert its action through multiple signaling mechanisms including membrane-initiated, cytoplasmic as
Acknowledgments
The authors thank members of their laboratories who contributed to the work described herein, especially Dr. Jian Qiu, Dr. Chunguang Zhang, Troy A. Roepke, Dr. Anna Malyala and Dr. Ms. Martha A. Bosch. Also, special thanks to Ms. Martha A. Bosch for her skilled assistance with the illustrations and manuscript preparation. The work from the authors’ laboratories was supported by PHS grants NS 43330, NS 38809 and DK 68098.
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