The digitalis-like steroid hormones: New mechanisms of action and biological significance

Maoz Nesher, Uri Shpolansky, Haim Rosen, David Lichtstein*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

142 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2093-2107
Number of pages15
JournalLife Sciences
Volume80
Issue number23
DOIs
StatePublished - 16 May 2007

Bibliographical note

Funding Information:
This work was supported by Grant No. 269.04 from the Israel Science Foundation.

Keywords

  • Digitalis
  • K-ATPase
  • Na
  • Natriuretic hormone
  • Ouabain
  • Steroids

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