J Korean Soc Endocrinol.  2003 Jun;18(3):272-282.

Interaction of Pituitary Adenylate Cyclase-Activating Polypeptide and Angiotensin II on Aldosterone Production in Human Adrenocortical H295R Cells

Affiliations
  • 1Department of Internal Medicine, Seoul National University College of Medicine, Korea.
  • 2The Institute of Endocrinology, Nutrition and Metabolism, Seoul National University Medical Research Center, Korea.
  • 3Center for Hormone Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.

Abstract

BACKGROUND: Evidence is accumulating that aldosterone secretion can be regulated in a paracrine and/or an autocrine manner by several neuropeptides locally released within the adrenal gland. Among neuropeptides, pituitary adenylate cyclase-activating polypeptide (PACAP) is present in high concentration in the human adrenal gland. The purpose of this study was to investigate the action of PACAP and the interaction between PACAP and angiotensin II (AII), the main physiologic aldosterone secretagogue, in aldosterone production in human H295R adrenocortical cells.
METHODS
H295R cells were incubated with increasing concentrations of PACAP (10(-11)M~10(-7)M) in the absence or presence of 10(-7)M AII. Aldosterone concentration in the supernatant was determined by RIA. Intracellular cAMP content was measured by RIA and total inositol phosphate (IP) production by anion exchange chromatography. Gene expression of CYP11B2 was studied by RT-PCR.
RESULTS
In H295R cells, PACAP stimulated aldosterone production in a dose-dependent manner. Incubation of H295R cells with PACAP in the presence of AII significantly increased aldosterone production, compared with that of PACAP alone. PACAP dose-dependently increased cAMP production, but 10(-7)M AII had no effect on either basal or PACAP-stimulated cAMP production. Total IP production was not affected by PACAP, but was increased by 10(-7)M AII; an increase that was not further increased by addition of PACAP. RT-PCR analysis of H295R cells which were exposed to 10-7M PACAP or 10(-7)M AII showed an increase in CYP11B2 transcript signal. Induction of CYP11B2 mRNA expression in response to treatment with both PACAP and AII was significantly more than that resulting from using PACAP alone.
CONCLUSION
The present study demonstrates that PACAP exerts a direct stimulatory effect on aldosterone production through induction of CYP11B2 mRNA expression by adenylate cyclase activation as the main intracellular signal pathway in H295R cells. Furthermore, there may be some additive effects between PACAP and AII on aldosterone production.


MeSH Terms

Adenylyl Cyclases
Adrenal Glands
Aldosterone Synthase
Aldosterone*
Angiotensin II*
Angiotensins*
Chromatography
Gene Expression
Humans*
Inositol
Neuropeptides
Pituitary Adenylate Cyclase-Activating Polypeptide*
RNA, Messenger
Signal Transduction
Aldosterone
Aldosterone Synthase
Angiotensin II
Angiotensins
Inositol
Neuropeptides
Pituitary Adenylate Cyclase-Activating Polypeptide
RNA, Messenger
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