Position Paper: Rapid responses to steroids: current status and future prospects

Abstract

Steroids exert their actions through several pathways. The classical genomic pathway, which involves binding of steroids to receptors and subsequent modulation of gene expression, is well characterized. Besides this, rapid actions of steroids have been shown to exist. Since 30 years, research on rapid actions of steroids is an emerging field of science. Today, rapid effects of steroids are well established, and are shown to exist for every type of steroid. The classical steroid receptors have been shown to be involved in rapid actions, but there is also strong evidence that unrelated structures mediate these rapid effects. Despite increasing knowledge about the mechanisms and structures which mediate these actions, there is still no unanimous acceptance of this category. This article briefly reviews the history of the field including current controversies and challenges. It is not meant as a broad review of literature, but should increase the awareness of the endocrinology society for rapid responses to steroids. As members of the organizing committee of the VI International Meeting on Rapid Responses to Steroid Hormones 2009, we propose a research agenda focusing on the identification of new receptoral structures and the identification of mechanisms of actions at physiological steroid concentrations. Additionally, efforts for the propagation of translational studies, which should finally lead to clinical benefit in the area of rapid steroid action research, should be intensified.

Juvenile hormone-activated phospholipase C pathway enhances transcriptional activation by the methoprene-tolerant protein

“…Many steroid hormones, including 17β-estradiol, use both membrane receptors and nuclear receptors to exert their effects (37). The primary estrogen effects are mediated by nuclear estrogen receptor alpha and estrogen receptor beta, which function as ligand-activated transcription factors.…”

ERα17p, an ERα P295-T311 fragment, modifies the migration of breast cancer cells, through actin cytoskeleton rearrangements

“…The extranuclear action of steroids and especially estradiol, has been primarily observed in the 60's [Szego and Davis, 1967], while a more exhaustive approach was conducted during the last two decades [see Kampa et al, 2008 andLevin, 2009;for reviews]. Despite the lack of consensus regarding the exact nature of the membrane estrogen binding counterparts, it has been proposed that they may include, in a non-exclusive way, the classical estrogen receptor alpha (ERa), or some alternatively spliced variants, anchored at the plasma membrane [Acconcia et al, 2005], a G-coupled membrane receptor, such as GPR30 (although this site is rather considered as a co-regulator than a real estrogen binding site), or a non-yet identified membrane protein [Thomas et al, 2005;Levin, 2009;Wendler et al, 2010]. Interestingly, GPR30 activation has been recently reported to increase the migration of breast cancer cells [Pandey et al, 2009], or breast cancer associated fibroblasts [Madeo and Maggiolini, 2010].…”

Mineralocorticoids in the Heart and Vasculature: New Insights for Old Hormones

“…In addition to the genomic action described above, aldosterone elicits rapid, nongenomic effects that involve various signaling pathways (61). These include pathways involving protein kinase C, Na + /H + exchange, intracellular calcium, the EGFR, and mitogen-activated protein kinase (MAPK) (Figure 3) (62).…”