Steroid and xenobiotic effects on the adrenal cortex: mediation by oxidative and other mechanisms

Peter J. Hornsby

Research output: Contribution to journalReview article

69 Scopus citations

Abstract

Because steroids reach high concentrations within the adrenal cortex, effects of the direct interaction of steroids and cytochrome P450 enzymes are possible and may involve damage. Steroid pseudosubstrate effects studied in cultured adrenocortical cells show that these effects are probably not mediated by steroid receptors. Release of oxidants during pseudosubstrate interaction with cytochrome P450s may be responsible for loss of enzymatic activity observed; enzyme activity can be protected by cytochrome P450 inhibitors, antioxidants, and lowered oxygen concentration. There may be pathological effects of pseudosubstrates in the adrenal cortex. Cytochrome P450/pseudosubstrate effects could be involved in the aging and death of adrenocortical cells in vivo, and necrosis of the adrenal cortex due to excessive ACTH stimulation or due to the action of adrenolytic chemicals could result from damage by oxygen radicals originating from cytochrome P450s. The possible mechanism of damage to the adrenal cortex by the xenobiotics dimethylbenzanthracene, TCDD, 3-methylcholanthrene, and o′, p′-DDD are reviewed.

Original languageEnglish (US)
Pages (from-to)103-115
Number of pages13
JournalFree Radical Biology and Medicine
Volume6
Issue number1
DOIs
Publication statusPublished - 1989

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Keywords

  • Adrenal cortex
  • Antioxidants
  • Cytochrome P450
  • Free radical
  • Oxidative damage
  • Pseudosubstrates
  • Steroids
  • Xenobiotics

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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