TY - JOUR
T1 - The digitalis-like steroid hormones
T2 - New mechanisms of action and biological significance
AU - Nesher, Maoz
AU - Shpolansky, Uri
AU - Rosen, Haim
AU - Lichtstein, David
N1 - Funding Information:
This work was supported by Grant No. 269.04 from the Israel Science Foundation.
PY - 2007/5/16
Y1 - 2007/5/16
N2 - Digitalis-like compounds (DLC) are a family of steroid hormones synthesized in and released from the adrenal gland. DLC, the structure of which resembles that of plant cardiac glycosides, bind to and inhibit the activity of the ubiquitous cell surface enzyme Na+, K+-ATPase. However, there is a large body of evidence suggesting that the regulation of ion transport by Na+, K+-ATPase is not the only physiological role of DLC. The binding of DLC to Na+, K+-ATPase induces the activation of various signal transduction cascades that activate changes in intracellular Ca++ homeostasis, and in specific gene expression. These, in turn, stimulate endocytosis and affect cell growth and proliferation. At the systemic level, DLC were shown to be involved in the regulation of major physiological parameters including water and salt homeostasis, cardiac contractility and rhythm, systemic blood pressure and behavior. Furthermore, the DLC system has been implicated in several pathological conditions, including cardiac arrhythmias, hypertension, cancer and depressive disorders. This review evaluates the evidence for the different aspects of DLC action and delineates open questions in the field.
AB - Digitalis-like compounds (DLC) are a family of steroid hormones synthesized in and released from the adrenal gland. DLC, the structure of which resembles that of plant cardiac glycosides, bind to and inhibit the activity of the ubiquitous cell surface enzyme Na+, K+-ATPase. However, there is a large body of evidence suggesting that the regulation of ion transport by Na+, K+-ATPase is not the only physiological role of DLC. The binding of DLC to Na+, K+-ATPase induces the activation of various signal transduction cascades that activate changes in intracellular Ca++ homeostasis, and in specific gene expression. These, in turn, stimulate endocytosis and affect cell growth and proliferation. At the systemic level, DLC were shown to be involved in the regulation of major physiological parameters including water and salt homeostasis, cardiac contractility and rhythm, systemic blood pressure and behavior. Furthermore, the DLC system has been implicated in several pathological conditions, including cardiac arrhythmias, hypertension, cancer and depressive disorders. This review evaluates the evidence for the different aspects of DLC action and delineates open questions in the field.
KW - Digitalis
KW - K-ATPase
KW - Na
KW - Natriuretic hormone
KW - Ouabain
KW - Steroids
UR - http://www.scopus.com/inward/record.url?scp=34248570330&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2007.03.013
DO - 10.1016/j.lfs.2007.03.013
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C2 - 17499813
AN - SCOPUS:34248570330
SN - 0024-3205
VL - 80
SP - 2093
EP - 2107
JO - Life Sciences
JF - Life Sciences
IS - 23
ER -