Mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces circulating melatonin levels in the rat

Toxicology
R PohjanvirtaJ Tuomisto

Abstract

We have previously shown that the prototype for halogenated aromatic hydrocarbons, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), diminishes serum melatonin concentration at the same dose in both the most TCDD-susceptible (Long-Evans, Turku AB; L-E) and the most TCDD-resistant (Han/Wistar, Kuopio; H/W) rat strain. The change developed within 24 h and persisted for at least 28 days after TCDD exposure; was independent of the time of day and was not associated with any morphological damage to the pineal gland. In the present study, we investigated the mechanism of this endocrine effect. Despite a 40-50% decrease in circulating melatonin levels, the pineal content of melatonin, serotonin and 5-hydroxyindole acetic acid remained unaltered and the rate-limiting enzyme of pineal melatonin biosynthesis, N-acetyltransferase, displayed only a relatively minor suppression in activity (30%) in TCDD-treated L-E rats. Likewise, TSDD did not influence the ability of pineal glands from L-E rats to synthesize and secrete melatonin in ex vivo or in vitro experiments. TCDD accelerated the disappearance of exogenous melatonin from the serum in both rat strains. This enhancement probably did not originate in the liver, because liver perfusion studies...Continue Reading

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Citations

Jul 27, 2000·Food Additives and Contaminants·L S Birnbaum, J Tuomisto
Oct 27, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dun-Xian TanRussel J Reiter
Nov 14, 1997·Toxicology and Applied Pharmacology·G M BlumenthalC J Portier
Feb 2, 2019·The European Journal of Neuroscience·Shelley A Tischkau
Feb 24, 2001·Journal of Endocrinological Investigation·A BaccarelliP A Bertazzi
Jun 23, 2000·Chemico-biological Interactions·M PesonenO Vakkuri
Sep 30, 2010·Chemical Reviews·Adelina M VoutchkovaPaul T Anastas

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