Rapid Actions of Steroid Hormones: Clinical Implications with Particular Reference to Hypoxia and Ischemia

Martin Wehling

《Adaptive Medicine》 9卷3期 (2017/09) Pp. 109-113

https://doi.org/10.4247/AM.2017.ABH183

摘要

For almost three decades the genomic model of delayed steroid action remained the dogmatic base explaining biological effects of steroid hormones. In 1985 there were about 10 papers on rapid, nongenomic steroid effects. Now, after 30 years of research, the existence of nongenomic steroid actions is no longer disputed. There are few reports to discuss the adaptation in animals and human beings caused by rapid steroid effects. So far, only very few of them have a clinical dimension. Neurosteroids represented an early exception though no longer used as anesthetics in humans. Yet, it is easily conceivable that nongenomic steroid actions are already being exploited unwittingly in the clinics, e.g. for glucocorticoids used at high doses in the treatment of anaphylaxia or asthma attacks. At the experimental level rapid steroid actions seem to be relevant to hypoxic or ischemic diseases such as cardiac or CNS hypoxia/ischemia. An early though failed example was that of neurosteroids to treat spinal trauma-related hypoxia. Unfortunately, clinical data were disappointing. Aldosterone antagonists were found to rapidly reduce infarct size and post-ischemic recovery in cardiac infarction animal models while aldosterone worsens cardiac ischemia in a canine model. Testosterone rapidly decreased myocardial recovery after ischemia. Estrogens were found to exert a cardioprotective effect in reperfusion damage presumably through their nonclassic, nongenomic receptor GPER. Dexamethasone rapidly improves reperfusion injury after ischemic muscle lesions in a rat muscular crush model and protects kidney function in experimental ischemia. Thyroid hormones nongenomically (through an integrin receptor) protect cardiac and CNS cells against ischemia/reperfusion damage, presumably by prevention of sodium and calcium overload typical for ischemic complications. For estrogens analogous neuroprotective effects mediated through extranuclear receptors were seen in CNS ischemia models with particular reference to hippocampal neurons. In elderly stroke patients, however, cortisol and estrogen levels were inversely correlated with functional outcomes. Most of these findings were attributed to intracellular signalling pathways such as ERK-kinases though it is too early to speculate on the exact mechanisms and their clinical relevance. If such effects could be translated into the clinically important field of ischemic diseases nongenomic actions of steroid hormones would enter a new era of biomedical relevance.

關鍵字

cardioprotection ； neuroprotection ； nongenomic action ； steroid hormones ； translation