Non-genomic actions of sex steroid hormones

Abstract

Steroid hormone receptors have been traditionally considered to act via the regulation of transcriptional processes, involving nuclear translocation and binding to specific response elements, and ultimately leading to regulation of gene expression. However, novel non-transcriptional mechanisms of signal transduction through steroid hormone receptors have been identified. These so-called 'nongenomic' effects do not depend on gene transcription or protein synthesis and involve steroid-induced modulation of cytoplasmic or cell membrane-bound regulatory proteins. Several relevant biological actions of steroids have been associated with this kind of signaling. Ubiquitous regulatory cascades such as mitogen-activated protein kinases, the phosphatidylinositol 3-OH kinase and tyrosine kinases are modulated through non-transcriptional mechanisms by steroid hormones. Furthermore, steroid hormone receptor modulation of cell membrane-associated molecules such as ion channels and Gprotein-coupled receptors has been shown. Tissues traditionally considered as 'non-targets' for classical steroid actions are instead found to be vividly regulated by non-genomic mechanisms. To this aim, the cardiovascular and the central nervous system provide excellent examples, where steroid hormones induce rapid vasodilatation and neuronal survival via non-genomic mechanisms, leading to relevant pathophysiological consequences. The evidence collected in the past years indicates that target cells and organs are regulated by a complex interplay of genomic and non-genomic signaling mechanisms of steroid hormones, and the integrated action of these machineries has important functional roles in a variety of pathophysiological processes. The understanding of the molecular basis of the rapid effects of steroids is therefore important, and may in the future turn out to be of relevance for clinical purposes.

Androgen receptor signaling pathways as a target for breast cancer treatment

“…In turn, these converge on the MAPK/ERK pathway with subsequent ERK translocation in the nucleus and interaction with transcriptional factors (TFs) regulating the expression of genes involved in cell proliferation. Moreover, in response to androgens, membranebound AR or plasma membrane G protein-coupled (Simoncini & Genazzani 2003, Li & Al-Azzawi 2009, Liao et al 2013 (Fig. 1).…”

Effects of androgens on cardiovascular remodeling

“…Initially, androgen enters the cells and binds to AR; the ligandbound AR then dimerizes and translocates into the nucleus, and binds to specific androgen response element sites located within the promoter regions of the target genes to modulate their transcriptional activities. Androgens also exert effects through extranuclear-nontranscriptional action, known as nongenomic action (Losel et al 2003, Simoncini & Genazzani 2003. Nongenomic androgen effects are distinct from genomic action in that they are exerted for a shorter time.…”

Effect of Gonadal Hormones on Colonic Contractile Activity in Albino Rats

“…The reason for the contradictory results could be a dose dependent action of TEST: In our study, we used supraphysiological concentrations. Similar to EST, TEST also acts via genomic (requiring gene transcription) and quick non-genomic pathways [45,46]. Our results showed no effect of TEST on ACh-induced contractions in male rats.…”