HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Solano, A. R. Articles by Podesta, E. J. Search for Related Content PubMed PubMed Citation Articles by Solano, A. R. Articles by Podesta, E. J.

Aldosterone secretion from adrenal glomerulosa cells can be stimulated by angiotensin II (AII), extracellular potassium and ACTH. Mitochondria from these cells respond to intracellular factors generated by AII (cyclic AMP (cAMP)-independent steroidogenesis) and ACTH (cAMP-dependent steroidogenesis), suggesting that the two signal-transduction mechanisms are linked by a common intermediate. We have evaluated this hypothesis by stimulating mitochondria from the unstimulated zona glomerulosa with a subcellular post-mitochondrial fraction (PMF) obtained from the zona glomerulosa after stimulation with AII or from the fasciculata gland after stimulation with ACTH; the subcellular fractions were also tested on mitochondria from fasciculata cells. PMFs obtained after incubation of adrenal zona glomerulosa with or without AII (0·1 µM) or ACTH (0·1 nM) were able to increase net progesterone synthesis 4·5-fold in mitochondria isolated from unstimulated rat zona glomerulosa. AII-pre-treated PMFs from the zona glomerulosa also stimulated steroidogenesis by mitochondria from zona fasciculata cells.

Separate experiments showed that inhibitors of arachidonic acid release and metabolism (bromophenacyl bromide, nordihydroguaiaretic acid, caffeic acid or esculetin) blocked corticosterone production in fasciculata cells stimulated with ACTH, suggesting that arachidonic acid could be the common intermediate in the actions of AII and ACTH on steroid synthesis. Evidence to support this concept was obtained from experiments in which the formation of an activated PMF by treatment of zona fasciculata with ACTH was blocked by the presence of the same inhibitors. Moreover, the inhibitory effects of these substances on PMF activation by ACTH were overcome by exogenous arachidonic acid and, in addition, arachidonic acid release was stimulated by ACTH.

We suggest that the mechanisms of action of ACTH and AII involve an increase in the release of arachidonic acid and conversion of arachidonic acid into lipoxygenase products. Both ACTH and AII may have a common intermediate, in spite of different membrane receptors and different signal-transduction mechanisms.

This article has been cited by other articles:

				R. Castilla, M. Gadaleta, A. F. Castillo, A. Duarte, I. Neuman, C. Paz, F. Cornejo Maciel, and E. J. Podesta New Enzymes Involved in the Mechanism of Action of Epidermal Growth Factor in a Clonal Strain of Leydig Tumor Cells Endocrinology, July 1, 2008; 149(7): 3743 - 3752. [Abstract] [Full Text] [PDF]

				F. Cornejo Maciel, P. Maloberti, I. Neuman, F. Cano, R. Castilla, F. Castillo, C. Paz, and E. J Podesta An arachidonic acid-preferring acyl-CoA synthetase is a hormone-dependent and obligatory protein in the signal transduction pathway of steroidogenic hormones J. Mol. Endocrinol., June 1, 2005; 34(3): 655 - 666. [Abstract] [Full Text] [PDF]

				V. E. Steele, C. A. Holmes, E. T. Hawk, L. Kopelovich, R. A. Lubet, J. A. Crowell, C. C. Sigman, and G. J. Kelloff Lipoxygenase Inhibitors as Potential Cancer Chemopreventives Cancer Epidemiol. Biomarkers Prev., May 1, 1999; 8(5): 467 - 483. [Abstract] [Full Text]

				X. Wang, L. P. Walsh, A. J. Reinhart, and D. M. Stocco The Role of Arachidonic Acid in Steroidogenesis and Steroidogenic Acute Regulatory (StAR) Gene and Protein Expression J. Biol. Chem., June 23, 2000; 275(26): 20204 - 20209. [Abstract] [Full Text] [PDF]