Nongenomic steroid actions: Completing the puzzle - Aldosterone as an example

In the common unidimensional theory of steroid action, steroids bind to int racellular receptors and modulate nuclear transcription and thus protein sy nthesis. These genomic steroid effects, being characterized by their delaye d onset of action and their dependence on transcription and protein synthes is, have been known for several decades. In contrast, very rapid actions of steroids, which are considered to be of nongenomic origin, have been recog nized more widely and characterized in detail only during the past ten year s. Specific rapid effects of steroids and related hormones like vitamin Us and thyroid hormones on cellular function involve a conventional second messen ger cascade which in most cases includes phospholipase C, phosphoinositide turnover, intracellular pH and intracellular calcium ([Ca2+](i)), and prote in kinase C. Furthermore, binding sites in membranes have been characterize d exposing binding features compatible with an involvement in rapid-steroid signaling. Characteristics of putative membrane receptors are completely d ifferent from those of classic intracellular steroid receptors; this also i ncludes the inability of classic steroid receptor antagonists to inhibit th ose rapid nongenomic steroid actions. The physiological and pathophysiological relevance of these effects is stil l largely unclear, but their existence has been proven recently even under in vivo conditions. New drugs modulating nongenomic steroid actions may fmd applications in various areas such as the cardiovascular and central nervo us systems, infertility and electrolyte homeostasis. This short review focuses mainly on the nongenomic actions of aldosterone a nd their cardiovascular implications.