Estrogen signalling pathway

Steroid hormones regulate a very extensive assembly of functions in numerous corporal tissues. Estrogens, the steroid hormones to which the majority of this chapter is dedicated, regulate from basic functions related to reproduction, the development of the skeleton, the maintenance of arterial tension, or diverse nervous functions. The molecular studies on the mechanism of action of estrogens have set the foundations that will permit us to understand how they carry out such diverse functions in such dissimilar tissues as well as how some substances that act through the estrogen signaling pathway can exercise opposite functions in different tissues. In this respect, there are five facts of particular importance that constitute the central nucleus of this revision ... 

McDonnell DP (2003) Mining the complexities of the estrogen signalling pathways for novel therapeutics. Endocrinology 144 4237-4240... 

In this way, although ERs participate in all cases and in all cells capable of responding to estrogens, the nature and intensity of the response is conditioned by the receptor interaction with three different types of molecules estrogen (steroid or not), DNA (through the HRE sequences), and the protein-protein interactions, including cofactors of transcription as well as elements of the signaling pathway from membrane receptors. 

Filardo EJ (2002) Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30 a novel signaling pathway with potential significance for breast cancer. J Steroid Biochem Mol Biol 80 231... 

Fig. 7.3. Osteoclastogenesis after estrogen deficiency. Estrogen deprivation leads to an increase in the synthesis of RANKL for stromal/OB cells of the BM. This increase in the expression of RANKL leads to an increase in OCS. Estrogen deficiency also induces the synthesis and secretion of cytokines, such as IL-6 and M-CSF, that increase the number of preosteoclasts in the BM, and thus increases OCS. Nonetheless, certain cells of the immune system, such as monocytes and T-cells, intervene in the process when the supply of estrogens fails. These cells secrete IL-1 and TNF-a that are powerful inductors of OCS. When estrogens or agonists of estrogen receptors like raloxifene are administered, the synthesis and secretion of many of the mentioned cytokines diminish and the synthesis and liberation of OPG and TGF-/S are stimulated. These molecules inhibit OCS by inhibiting the RANKL/RANK signal pathway and by promoting osteoclast apoptosis...

The ER transduction signal pathway in MCF7 as a model for estrogenicity... 

Malyala A, Kelly MJ, Ronnekleiv OK Estrogen modulation of hypothalamic neurons activation of multiple signaling pathways and gene expression changes. Steroids. 2005 70 397 F06. 

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