Lipoxygenase products as common intermediates in cyclic AMP-dependent and -independent adrenal steroidogenesis in rats.
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 microM) or ACTH (0.1 nM) were able to increase net progesterone synthesis 4.5-fold in mitochondria isolated from unstimulated rat zona glomerulosa. AII-pretreated 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Solano
A R
AR
Hormones and Cell Regulation Laboratories, Hospital de Niños, Buenos Aires, Argentina.
Dada
L
L
Podesta
E J
EJ
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000493:pharmacokinetics; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000493:pharmacokinetics; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001681:Biological Assay; D000242:Cyclic AMP / Q000378:metabolism*; D008084:Lipoxygenase / Q000096:biosynthesis*; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D015383:Zona Fasciculata / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D001095:Arachidonic Acids; D000804:Angiotensin II; D016718:Arachidonic Acid; D000450:Aldosterone; D011374:Progesterone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D008084:Lipoxygenase