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Steroid and sterol 7-hydroxylation: ancient pathways

Authors
Journal
Steroids
0039-128X
Publisher
Elsevier
Publication Date
Volume
67
Issue
12
Identifiers
DOI: 10.1016/s0039-128x(02)00044-2
Keywords
  • Cholesterol
  • Cytochrome P450
  • Cyp7B
  • Dhea
  • Evolution
  • Receptor
  • Steroid
  • Hypothesis
  • Review

Abstract

Abstract B-ring hydroxylation is a major metabolic pathway for cholesterols and some steroids. In liver, 7α-hydroxylation of cholesterols, mediated by CYP7A and CYP39A1, is the rate-limiting step of bile acid synthesis and metabolic elimination. In brain and other tissues, both sterols and some steroids including dehydroepiandrosterone (DHEA) are prominently 7α-hydroxylated by CYP7B. The function of extra-hepatic steroid and sterol 7-hydroxylation is unknown. Nevertheless, 7-oxygenated cholesterols are potent regulators of cell proliferation and apoptosis; 7-oxygenated derivatives of DHEA, pregnenolone, and androstenediol can have major effects in the brain and in the immune system. The receptor targets involved remain obscure. It is argued that B-ring modification predated steroid evolution: non-enzymatic oxidation of membrane sterols primarily results in 7-oxygenation. Such molecules may have provided early growth and stress signals; a relic may be found in hydroxylation at the symmetrical 11-position of glucocorticoids. Early receptor targets probably included intracellular sterol sites, some modern steroids may continue to act at these targets. 7-Hydroxylation of DHEA may reflect conservation of an early signaling pathway.

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