4-methylbenzylidene-camphor (4MBC) causes pituitary effects comparable to hypothyroidism
IH Hamann1, C Schmutzler1, P Kirschmeyer2, H Jarry2 & J Köhrle1
4-methylbenzylidene-camphor (4MBC) is an endocrine active compound used as an UV absorber in sunscreens and other cosmetics such as anti-aging lotions and day care products. 4MBC shows weak estrogenic effects on the reproductive system but strong anti-osteoporotic effects after chronic application (Seidlova-Wuttke D et al. 2005 Toxicol Appl Pharmacol. 24:in press). Additionally, 4MBC can be resorbed through the skin (Janjua NR et al. 2004 J Invest Dermatol. 123:57-61).
Experimental set-up: Two month old female Sprague-Dawley rats in groups of 12 animals were treated per gavage with five concentrations of 4MBC (10, 33, 100, 333, 600 mg/kg b.w./day) over a period of five days on a background of a soy-free diet two weeks after bilateral ovariectomy. We used T4, the antithyroidal drug methimazole (MMI), and estradiol benzoate (E2) as controls. Total T3, T4, and TSH serum levels were measured by RIA; the expression of TSHα, TSHβ, 5′-deiodinase type I (5′DI) and II (5′DII) transcript levels in the pituitary were detected by real time RT-PCR.
TSH serum levels were significantly elevated from concentrations of 33 mg 4MBC/kg b.w., while T4 serum levels were slightly decreased and T3 levels almost unchanged. This serum data are typical for beginning hypothyroidism, when the peripheral organs maintain T3 serum levels during the initial phase of the disease. In the pituitary TSHα and TSHβ were markedly increased from concentrations of 33 mg/kg b.w. (≥ 2 fold change). 5′DI mRNA levels decreased proportional to the concentrations of 4MBC applied, while 5′DII transcript levels were elevated. The controls treated with T4 and MMI behaved as described in the literature. Additionally, the weight of the thyroid glands was remarkably increased after five days of treatment at concentrations exceeding 33 mg/kg b.w. These results indicate that 4MBC is a potent inhibitor of the pituitary-thyroid-axis.