Mellanen, P; Petänen, T; Lehtimäki, J; Mäkelä, S; Bylund, G; Holmbom, B; Mannila, E; Oikari, A; Santti, R
The wood-derived compound, beta-sitosterol (purity >90%), was shown to be estrogenic in fish. It induced the expression of the vitellogenin gene in the liver of juvenile and methyltestosterone-treated rainbow trout. Structural similarities to p-sitosterol notwithstanding, cholesterol, citrostadienol, beta-sitostanol, and 5-androstene-3 beta,17 beta-diol, an estrogenic member of the androstenic steroid group, were inactive. An abietic acid mixture (37% abietic acid, 6% dehydroabietic acid, and a remainder of unknown compounds) showed slight hormonal activity in feed, but it was completely inactive when given intraperitoneally in implants. The estrogenic component of the abietic acid preparation was not identified. In addition to beta-sitosterol and abietic acid, several other wood-derived compounds including betulin, isorhapontigenin, isorhapontin, and pinosylvin were estrogenic in breast cancer cells (MCF-7 or T-47D). However, betulin and pinosylvin, available in sufficient amounts for in vivo testing, did not induce the expression of the vitellogenin gene. Differences in the primary sequences of human and fish estrogen receptors (hormone as well as DNA-binding regions) or uptake and metabolism of the compounds may explain the discrepancy between the two estrogen bioassays. Wood-derived compounds such as beta-sitosterol, present in pulp and paper mill effluents, may account for the weak estrogenicity of debarking effluent seen at the vitellogenin expression bioassay.