The endocrine active compound 4-methylbenzylidene-camphor (4-MBC) is frequently used as an UV absorber in sunscreens and various skin care products. Though 4-MBC is weakly estrogenic in the reproductive system of fishes and rodents it shows strong anti-osteoporotic effects. Furthermore, different studies show percutanous absorption of 4-MBC after dermal administration resulting in identical biotransformation in humans and rats. Female Sprague-Dawley rats received five concentrations of 4-MBC (10600 mg/kg per b.w. days) via gavage over a period of five days on a background of a soy-free diet. As controls for the thyroid axis served T4 and the antithyroidal drug methimazole (MMI), while E2 was used to evaluate estrogenic effects. TSH, total T4 and T3 were measured by RIA. Transcript levels of genes involved in the feedback control in the pituitary (αGSu, Tshβ, 5′-deiodinases (Dio1, Dio2)) as well as gene expression of TSH receptor (Tshr), sodium-iodide symporter (Nis) and thyroid peroxidase (Tpo) in the thyroid gland were detected by Real-time RT-PCR. TSH serum levels were significantly elevated at concentrations ≥33 mg 4 MBC/kg while T4 serum levels were slightly decreased, and T3 levels remained almost unchanged, which 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 >33 mg/kg. Dio1 gene expression was down-regulated while Dio2 transcript levels were increased depending on the 4-MBC concentration applied. Moreover, the animals exhibited remarkably increased thyroid gland weights at concentrations exceeding 33 mg/kg. The data on increased gene expression of Tshr, Nis and Tpo in the thyroid gland were supported by immunohistochemistry. These data are consistent with decreased Dio1 activity in the liver, indicating that 4-MBC is a potent inhibitor of the pituitarythyroidaxis.
03 - 07 May 2008
European Society of Endocrinology