Estrogens gene regulation

Saltiere-Imerly R.B., Young B.J. and Capozza M.A. (1989). Estrogen differentially regulates neuropeptide gene expression in a sexually dimorphic olfactory pathway. Proc Natl Acad Sci 86, 4766-4770. 

Fig. 1.7. Interaction of receptor with hormone response element. The hormone response elements are located in the promoter region of genes regulated by hormones with nuclear receptors. They are constituted of sequences from 13 to 15 nucleotides. The elements of estrogen response are formed by two semi-elements, which are sequences of 5 nucleotides, and a spacer of 3 unspecific nucleotides (n). The interaction is produced so that the section of the zinc fingers of the receptor lodges in the main furrow of the DNA double helix...

Mitchner NA, Garlick C, Ben-Jonathan N (1998) Cellular distribution and gene regulation of estrogen receptors a and f) in the rat pituitary gland. Endocrinology 139 976-3983... 

FIGURE 23.3 Example of the gene regulation patterns induced by a biological stimulus in responsive cells, in this case human breast cancer cells stimulated with a mitogenic dose of estrogens. 

Murdoch, F.E. and Gorski, J., The role of ligand in estrogen receptor regulation of gene... 

Garban, H.J., Marquez-Garban, D.C., Pietras, R.J., and Ignarro, LJ. (2005). Rapid nitric oxide-mediated S-nitrosylation of estrogen receptor regulation of estrogen-dependent gene transcription. Proc. Nad. Acad. Sci. USA 102,2632-2636. 

Fig. 6.2. Proposed mechanisms of action of pure antiestrogens (fulvestrant). 1 Fulvestrant (ICI) binds to estrogen receptor (ER). 2 Fulvestrant binding to ER accelerates receptor degradation ( ER down-regulator ). 3 Rate of dimerization and nuclear localization of fulvestrant-ER complex is reduced. 4 Reduced binding of fulvestrant-ER to ERE. 5 No transcription of estrogen-responsive genes since AF-1 and AF-2 are inactive, no coactivators are recruited and the activity of RNA polymerase II is not activated (or inhibited) (Wakeling 2000)...

The proposed model to explain OCS is schematized in Fig. 7.2. Several agents, induced or not for estrogen deficiency, stimulate the expression of RANKL on stromal/OB cells. The binding of RANKL with its receptor RANK on osteoclastic precursors, together with M-CSF, is a necessary and sufficient condition to carry out all the steps in the formation and differentiation of the osteoclasts. Undoubtedly all this is much more complex than what is described here since at least 24 genes that positively and negatively regulate OCS have been described (Boyle et al. 2003). 

---