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  • Furthermore certain components in the Melanocyte Growth


    Furthermore, certain components in the Melanocyte Growth Medium seem to influence the response to UV radiation [17]: UV-induced effects on tyrosinase activity were less distinct in melanocytes cultured with phorbol 12-myristate 13-acetate [18], which was also an ingredient in our Melanocyte Growth Medium. This could also be the reason that an increase in tyrosinase activity was not observed. The rationale for our study was the surprising observation of a clinical trial that women who had used an oral contraceptive composed of ethinylestradiol and CMA experienced pigmentary alterations less commonly than before therapy began. Our data suggest that this clinical observation may be due to an inhibitory effect of CMA on melanocytes. Comparative studies with other progestogens apart from CMA would be necessary to further test this hypothesis. Many progestogens are used as compounds in oral contraceptives, such as levonorgestrel, norethisterone, norgestimate, desogestrel, gestodene, lynestrenol, drospirenone, dienogest and cyproterone acetate. Except for one study on cyproterone acetate, no other information on the effects of progestogens on human melanocytes is available. In that study, Tadokoro et al. [25] showed that an androgen-triggered stimulation of tyrosinase activity in genital melanocytes could be antagonized by cyproterone acetate. Significant inhibitory effects of progestogens on the proliferation of melanocytes in monoculture are shown for the first time in the present study. However, other BIBR 1532 in the skin, such as keratinocytes, may influence pigmentation [26]. Therefore, the effect of hormones should be tested in other models, such as co-cultures [27] or reconstructed human skin [28], [29]. Finally, clinical studies in humans are necessary to further delineate differences in pigmentary abnormalities with different hormonal contraceptives, leading to reduction of the prevalence of cosmetically unwanted changes, such as melasma.
    Introduction In animal farming, estrogens and progestogens are mainly applied as growth-promoters [1], and in developing single-sex populations of fish in aquaculture [2], [3], [4], [5]. The discovery of toxicological effects on wildlife [6] and the lack of clarity about their potential impacts on ecosystems and human health have raised public concern about their occurrence in the environment. Because of their physical and chemical properties, many of these substances or their metabolites end up in the environment, where they can have adverse effects on wildlife organisms. Many studies have confirmed the presence of estrogens and progestogens at concentrations of toxicological concern in the aquatic environment. Even at very low concentrations of ∼1 ng/l, endocrine-disrupting effects, such as decreased fertility, feminization and hermaphroditism of aquatic organisms, are assigned to this class of steroidal hormones [7], [8], [9]. Because of their strong endocrine-disrupting potency, special attention has been given to the natural estrogens, estradiol and estrone, as well as to the synthetic estrogen, ethynyl estradiol. Steroid sexual hormones enter the aquatic environment mainly via effluents from waste water treatment plants (WWTPs) (after incomplete removal in the plant) [10], [11]. Once in waterways, they may sorb to solid particles (bed sediments, soils) where estrogens and progestogens may persist for long periods [12].
    Fate and distribution in the environment
    Analytical methodologies Several analytical methods for detecting estrogens and progestogens in water samples have been reported. They usually comprise an extraction step, eventual clean up, and analysis (e.g., solid phase extraction (SPE), followed by chromatographic separation with mass-spectrometric (MS) detection). However, there is little documentation on their analysis in solid samples and very often methods applied to these matrices are simple adaptations (incorporating additional purification steps) of those used for analyzing water samples. This article reviews the very few methods utilized for analysis of sediments and sludge samples. Table 2 shows schematically the main procedural steps of these methodologies.