Leukotrienes as common intermediates in the cyclic AMP dependent and independent pathways in adrenal steroidogenesis

Angela R. Solang, Laura A. Dada, Maria Luz Sardanons, Mercedes L. Sánchez, Ernesto J. Podestá*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Aldosterone secretion from adrenal glomerulosa cells can be stimulated by angiotensin II (All), extracellular potassium and adrenocorticotropin (ACTH). Since the mitochondria can recognize factors generated by All (cyclic-AMP-independent) and ACTH (cyclic AMP dependent), it is reasonable to postulate the existence of a common intermediate in spite of a different signal transduction mechanism. We have evaluated this hypothesis by stimulation of mitochondria from glomerulosa gland with fractions isolated from glomerulosa gland stimulated with All or from fasciculata gland stimulated with ACTH; the same fractions were tested using mitochondria from fasciculata cells. Post-mitochondrial fractions (PMTS) obtained after incubation of adrenal zona glomerulosa with or without All (10-7 M) or ACTH (10-10 M), were able to increase net progesterone synthesis 5-fold in mitochondria isolated from non-stimulated rat zona glomerulosa. In addition, All in zona glomerulosa produced in vitro steroidogenic fractions that were able to stimulate mitochondria from zona fasciculata cells. Inhibitors of arachidonic acid release and metabolism blocked corticosterone production in fasciculata cells stimulated with ACTH. This concept is supported by the experiment in which bromophenacyl-bromide and nordihydroguaiaretic acid also blocked the formation of an activated PMTS. In fact, non-activated PMTS, in the presence of exogenous arachidonic acid AA, behaved as an activated PMTS from ACTH stimulated cells. We suggest that the mechanisms of action of ACTH and All involve an increase in the release of AA and an activation of the enzyme system which converts AA in leukotriene products.

Original languageEnglish (US)
Pages (from-to)745-751
Number of pages7
JournalJournal of Steroid Biochemistry
Volume27
Issue number4-6
DOIs
StatePublished - 1987

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

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