Control of Aldosterone Secretion: A Model for Convergence in Cellular Signaling Pathways

Research output: Contribution to journalReview article

334 Citations (Scopus)

Abstract

Aldosterone secretion by glomerulosa cells is stimulated by angiotensin II (ANG II), extracellular K+, corticotrophin, and several paracrine factors. Electrophysiological, fluorimetric, and molecular biological techniques have significantly clarified the molecular action of these stimuli. The steroidogenic effect of corticotrophin is mediated by adenylyl cyclase, whereas potassium activates voltage-operated Ca2+ channels. ANG II, bound to AT1 receptors, acts through the inositol 1,4, 5-trisphosphate (IP3)-Ca2+/calmodulin system. All three types of IP3 receptors are coexpressed, rendering a complex control of Ca2+ release possible. Ca2+ release is followed by both capacitative and voltage-activated Ca2+ influx. ANG II inhibits the background K+ channel TASK and Na+-K +-ATPase, and the ensuing depolarization activates T-type (Ca v3.2) Ca2+ channels. Activation of protein kinase C by diacylglcerol (DAG) inhibits aldosterone production, whereas the arachidonate released from DAG in ANG II-stimulated cells is converted by lipoxygenase to 12-hydroxyeicosatetraenoic acid, which may also induce Ca2+ signaling. Feedback effects and cross-talk of signal-transducing pathways sensitize glomerulosa cells to low-intensity stimuli, such as physiological elevations of [K+] (≤1 mM), ANG II, and ACTH. Ca2+ signaling is also modified by cell swelling, as well as receptor desensitization, resensitization, and downregulation. Long-term regulation of glomerulosa cells involves cell growth and proliferation and induction of steroidogenic enzymes. Ca2+, receptor, and nonreceptor tyrosine kinases and mitogen-activated kinases participate in these processes. Ca 2+- and cAMP-dependent phosphorylation induce the transfer of the steroid precursor cholesterol from the cytoplasm to the inner mitochondrial membrane. Ca2+ signaling, transferred into the mitochondria, stimulates the reduction of pyridine nucleotides.

Original languageEnglish
Pages (from-to)489-539
Number of pages51
JournalPhysiological reviews
Volume84
Issue number2
DOIs
Publication statusPublished - Apr 1 2004

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Physiology (medical)

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