Non-Genomic Action of Sex Steroid Hormones

Abstract

Abstract:This chapter aims at giving a concise, up-to-date view of the non-genomic action of sex-steroid hormones and some related aspects. It includes an overview of the identity of the receptors mediating non-genomic action. To date, classical steroid receptors are known to be the principal mediators of this action, although there is now evidence that G-protein coupled receptors have a similar role. Non-genomic action has been separately analyzed in classical hormone-responsive cells (reproductive cells) and non-classical hormone-responsive cells (non-reproductive cells). With this distinction we intend to underline the different biological responses induced by the non-genomic action of steroids in these two cell types depending on their different functions, as well as the low level of receptor expression in some non-classical hormone-responsive cells, which might explain the absence of receptor transcriptional activity in such cells. One section focuses on the reversible integration between extra-nuclear and nuclear hormone action. Activation of kinase cascades by steroid hormones produces different effects in the cell nuclei. In addition to receptor or co-activator modifications, chromatin remodeling, receptor nuclear export, and increased expression of signaling effectors have been observed. The final section deals with the cross talk between growth factor and steroid signaling, a process which links hormonal and growth factor receptors, and regulates important cell functions. We apologize to scientists working in this area whose reports are not mentioned or extensively discussed owing to space limitations. INTRODUCTIONSteroid hormone action is mediated by ligand-regulated transcriptional factors whose activity requires either direct interaction with target DNA sequences or association with proteins that in turn bind discrete nucleotide sequences. Thereafter, gene expression modification occurs, protein expression changes, and finally hormonal effects become evident. The entire process requires a relatively long time, from several minutes to hours or days. In contrast, non-genomic hormonal actions are rapid. They activate pathways that transduce signals from the cell membrane to the cell interior and are insensitive to RNA and protein synthesis inhibitors. Although the rapid, non-genomic actions of steroid hormones have only recently been intensively 365

Steroid signaling activation and intracellular localization of sex steroid receptors

“…In different cell types extra-nuclear AR mediates rapid activation of signaling effectors, such as Src, PI3-K and MAPK (reviewed in Migliaccio et al 2010). Thus, the extranuclear location of AR dictates these rapid effects, which lead to cell cycle regulation, cell growth in mouse model of prostate cancer, survival and cytoskeleton changes (Peterziel et al 1999;Migliaccio et al 2000Migliaccio et al , 2007Kousteni et al 2001;Castoria et al 2003).…”

“…Thus, non‐genomic action mediated by SRs regulates the downstream genomic effects of sex steroids. Conversely, transcriptional activity of sex steroid receptors controls signaling pathway activation ( reviewed in Migliaccio et al 2010; Vicent et al 2010). Figure 1 depicts the two models of sex steroid action and their possible integration in target cells.…”

Androgen Receptor-Dependent Mechanisms Mediating Drug Resistance in Prostate Cancer

“…Therefore, the study was terminated early, although the study cohort was not complete [ 81 ]. Interestingly, Src can form a ternary complex with AR and the estrogen receptor and thereby, activate Erk-2 resulting in increased proliferation of PCa cells [ 82 , 83 ]. Also, this ternary complex regulates EGF-induced EGFR leading to enhanced DNA synthesis and mitogenesis.…”

“…Also, this ternary complex regulates EGF-induced EGFR leading to enhanced DNA synthesis and mitogenesis. Toremifene, a selective estrogen receptor modulator showed beneficial effects in PCa treatment [ 82 , 83 ].…”