Steroid and sterol 7-hydroxylation: ancient pathways

Richard Lathe

Research output: Contribution to journalArticlepeer-review

Abstract

B-ring hydroxylation is a major metabolic pathway for cholesterols and some steroids. In liver, 7alpha-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 7alpha-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 modem steroids may continue to act at these targets. 7-Hydroxylation of DHEA may reflect conservation of an early signaling pathway.

Original languageEnglish
Pages (from-to)967-977
Number of pages11
JournalSteroids
Volume67
Issue number12
DOIs
Publication statusPublished - Nov 2002

Keywords

  • Apoptosis
  • Cholesterol
  • Cholesterol 7-alpha-Hydroxylase
  • Cytochrome P-450 Enzyme System
  • Homeostasis
  • Hydroxylation
  • Isomerism
  • Receptors, Steroid
  • Steroid Hydroxylases
  • Sterols
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Review

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