Exp Clin Endocrinol Diabetes 2007; 115 - P02_014
DOI: 10.1055/s-2007-972421

4-methylbenzylidene-camphor (4MBC) causes effects comparable to primary hypothyroidism

I Gotthardt 1, C Schmutzler 1, P Kirschmeyer 2, W Wuttke 2, H Jarry 2, J Köhrle 1
  • 1Charité – Universitätsmedizin Berlin, Institut für Experimentelle Endokrinologie, Berlin, Germany
  • 2Zentrum für Frauenheilkunde der Georg-August-Universität Göttingen, Abteilung Klinische und Experimentelle Endokrinologie, Göttingen, Germany

4-methylbenzylidene-camphor (4MBC) is an UV absorber frequently used in sunscreens and various daily cosmetics. Though 4MBC is weakly estrogenic in the reproductive system of fishes and rodents it shows strong anti-osteoporotic effects comparable to E2 after chronic application (Seidlova-Wuttke D et al. 2006). Moreover, 4MBC is resorbed through the skin after dermal administration resulting in identical biotransformation of this UV filter in humans and rats (Janjua NR et al. 2004; Schauer UM et al. 2006).

Two month old female, bilaterally ovariectomized Sprague-Dawley rats received five concentrations of 4MBC (10, 33, 100, 333, 600mg/kg b.w./d) via gavage over a period of five days on the background of a soy-free diet. As controls for the thyroid axis served T4 and the antithyroidal drug methimazole (MMI), while estradiol benzoate (E2, 600µg/kg b.w./d) was used to evaluate estrogenic effects. TSH, total T4 and T3 serum levels were measured by RIA. The transcript levels of αGSu, TSHβ, 5'-deiodinase type I (5'DI) and II (5'DII) in the pituitary, as well as TSH receptor (Tshr) and the basolateral sodium-iodide symporter (NIS) in the thyroid gland were detected by real time RT-PCR.

TSH serum levels were significantly elevated at concentrations ≥33mg 4MBC/kg b.w., while T4 serum levels were slightly decreased and T3 levels almost unchanged. This finding is typical for the initial phase of hypothyroidism when the peripheral organs still maintain T3 serum levels. In the pituitary αGSu and TSHβ were markedly increased at concentrations >33mg/kg b.w. (≥2-fold change). 4MBC decreased 5'DI mRNA levels while 5'DII transcript levels were increased depending on the applied 4MBC concentration. Additionally, the thyroid gland weights were remarkably increased after five days of treatment at concentrations exceeding 33mg/kg b.w..

These results are consistent with increased transcript levels of Tshr and NIS indicating that 4MBC is a potent inhibitor of the pituitary-thyroid-axis.

Supported by EURISKED and a PhD Student Fellowship of the Charité.