Exp Clin Endocrinol Diabetes 2005; 113 - 138
DOI: 10.1055/s-2005-862997

4MBC and OMC, components of UV-sunscreens, exert organ specific alterations on type I 5'-Deiodinase activity and expression in female rats

I Hamann 1, P Hofmann 1, C Schmutzler 1, B Mentrup 1, K Huhne 1, H Jarry 2, D Seidlová-Wuttke 2, W Wuttke 2, J Köhrle 1
  • 1Charite, Experimentelle Endokrinologie, Berlin
  • 2Universitäts-Frauenklinik, Klinische und Experimentelle Endokrinologie, Göttingen

Endocrine disrupting compounds (EDC) of natural or synthetic origin were originally found to impair development and endocrine regulation of the reproductive system. Here, we assessed whether they also exert effects on the thyroid hormone axis. Female ovariectomized rats were treated for 12 weeks with two substances used as UV absorbers in sunscreens: Octyl-methoxycinnamate (OMC; 66 and 310mg/day) and 4-methylbenzylidene-camphor (4-MBC; 0.4 and 1.74mg/day) alone or in combination with soy-containing food. These substances are known to be resorbed by the skin, circulating in the blood (Janjua et al. 2004J Invest Dermatol 123:57–61) and suspected to have endocrine disrupting effects. The soy isoflavone genistein has estrogenic and anti-estrogenic effects and is known to inhibit thyroid hormone biosynthesis. As type I 5'-deiodinase (5'DI) is a well known T3-regulated endpoint, 5'DI activity was measured by deiodination of 125I--reverse T3, and 5'DI gene expression was determined by real time RT-PCR. Treatment with OMC caused a significant reduction of 5'DI activity from a basal level of 6.6 to 3.0 and 3.1 pmol iodide released x mg–1 x min–1 in the liver in the absence and presence of soy in the diet, respectively, while 4MBC did not show any effects. A similar decrease was also observed for 5'DI mRNA levels. In the kidney OMC as well as 4MBC led to a marked decline of 5'DI activity from 8.4 to 3.0 pmol iodide released x mg–1 x min–1, independent of the diet. Additionally, higher 5'DI activities were found in the kidney of animals consuming soy containing diet, while no such effect was obtained in liver. This data indicates that 4MBC and OMC affect thyroid hormone metabolism via tissue-specific inhibition of 5'DI activity and gene expression. Thus, 4MBC and OMC do not only interfere with steroid-hormone dependent regulation, but may also disturb endocrine regulation via the thyroid hormone axis.

Supported by EU Grant “Multi-Organic Risk Assessment of Selected Endocrine Disrupters“.