Experientia

, Volume 51, Issue 4, pp 349–355 | Cite as

Hepatic hydroxylation of melatonin in the rat is induced by phenobarbital and 7,12-dimethylbenzy[a]anthracene — implications for cancer etiology

  • G. Praast
  • C. Bartsch
  • H. Bartsch
  • D. Mecke
  • T. H. Lippert
Research Articles

Abstract

The protective function of the pineal hormone melatonin in the etiology of cancer and carcinogenic activation is increasingly well-established. Low melatonin levels seem to parallel cancer growth. The question arises as to which factors cause the depression of melatonin levels and what the direct effects are. Melatonin is known to be metabolized in the liver by hydroxylation and subsequent conjugation yielding 6-sulfatoxymelatonin as a main product. Nevertheless, the microsomal monoxygenases catalyzing the first step have been poorly investigated. To further characterize these enzymes, typical inducers of three different sub-classes, namely phenobarbital, 7,12-dimethylbenz[a]anthracene, and 17β-estradiol, were administered to female Fischer rats. Circadian urinary excretion patterns of melatonin and 6-sulfatoxymelatonin were determined over a 24-hour period on the third (second) day of induction. Liver homogenates were used to monitor the in vitro conversion of melatonin or 6-hydroxymelatonin to 6-sulfatoxymelatonin. Results of both approaches showed the microsomal monoxygenases catalyzing the 6-hydroxylation of melatonin to be strongly inducible by phenobarbital and to a lesser degree by the polyaromatic hydrocarbon 7,12-dimethylbenz[a]anthracene. The dramatic depletion of circulating melatonin as a result of these induction patterns and its possible implications for oncogenesis are discussed.

Key words

Dimethylbenz[a]anthracene estradiol phenobarbital melatonin 6-sulfatoxymelatonin hepatic metabolism urinary excretion cancer etiology 

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Copyright information

© Birkhäuser Verlag Basel 1995

Authors and Affiliations

  • G. Praast
    • 1
  • C. Bartsch
    • 1
  • H. Bartsch
    • 1
  • D. Mecke
    • 2
  • T. H. Lippert
    • 1
  1. 1.Section of Clinical Pharmacology, Department of GynaecologyUniversity of TübingenTübingenGermany
  2. 2.Institute of Physiological ChemistryUniversity of TübingenTübingenGermany

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