Signaling interactions in the adrenal cortex

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The major physiological stimuli of aldosterone secretion are angiotensin II (AII) and extracellular K+, whereas cortisol production is primarily regulated by corticotropin (ACTH) in fasciculata cells. AII triggers Ca2+ release from internal stores that is followed by store-operated and voltage-dependent Ca2+ entry, whereas K+-evoked depolarization activates voltage-dependent Ca2+ channels. ACTH acts primarily through the formation of cAMP and subsequent protein phosphorylation by protein kinase A. Both Ca2+ and cAMP facilitate the transfer of cholesterol to mitochondrial inner membrane. The cytosolic Ca2+ signal is transferred into the mitochondrial matrix and enhances pyridine nucleotide reduction. Increased formation of NADH results in increased ATP production, whereas that of NADPH supports steroid production. In reality, the control of adrenocortical function is a lot more sophisticated with second messengers crosstalking and mutually modifying each other's pathways. Cytosolic Ca2+ and cGMP are both capable of modifying cAMP metabolism, while cAMP may enhance Ca2+ release and voltage-activated Ca2+ channel activity. Besides, mitochondrial Ca2+ signal brings about cAMP formation within the organelle and this further enhances aldosterone production. Maintained aldosterone and cortisol secretion are optimized by the concurrent actions of Ca2+ and cAMP, as exemplified by the apparent synergism of Ca2+ influx (inducing cAMP formation) and Ca2+ release during response to AII. Thus, cross-actions of parallel signal transducing pathways are not mere intracellular curiosities but rather substantial phenomena, which fine-tune the biological response. Our review focuses on these functionally relevant interactions between the Ca2+ and the cyclic nucleotide signal transducing pathways hitherto described in the adrenal cortex.

Original languageEnglish
Article number17
JournalFrontiers in Endocrinology
Volume7
Issue numberFEB
DOIs
Publication statusPublished - 2016

Fingerprint

Adrenal Cortex
Aldosterone
Angiotensin II
Adrenocorticotropic Hormone
Hydrocortisone
Signal Transduction
Cyclic Nucleotides
Mitochondrial Membranes
Second Messenger Systems
Cyclic AMP-Dependent Protein Kinases
NADP
Organelles
NAD
Nucleotides
Adenosine Triphosphate
Steroids
Cholesterol
Phosphorylation
Proteins

Keywords

  • ACTH
  • Aldosterone
  • Angiotensin II
  • Ca signal
  • cAMP
  • Cortisol
  • Mitochondria
  • Potassium ion

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Signaling interactions in the adrenal cortex. / Spät, A.; Hunyady, L.; Szanda, G.

In: Frontiers in Endocrinology, Vol. 7, No. FEB, 17, 2016.

Research output: Contribution to journalArticle

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