Inhibition of imidazole-induced tyrosinase activity by estradiol and estriol in cultured B16/C3 melanoma cells

• Published in: Journal of cellular physiology Vol. 134; no. 3; p. 497
• Main Authors: Kline, E L, Smith, T J, Carland, K A, Blackmon, B
• Format: Journal Article
• Language: English
• Published: United States 01.03.1988
• Subjects: Animals; Catechol Oxidase - biosynthesis; Cell Division - drug effects; Dactinomycin - pharmacology; Dose-Response Relationship, Drug; Enzyme Induction - drug effects; Estradiol - pharmacology; Estriol - pharmacology; Imidazoles - pharmacology; Melanoma; Monophenol Monooxygenase - biosynthesis; Monophenol Monooxygenase - genetics; Protein Biosynthesis; RNA, Messenger - genetics; Tumor Cells, Cultured
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041340324

The effect of estrogens on tyrosinase (EC 1.14.18.1) activity was studied in B16/C3 melanoma cultures. Estradiol, estriol, and other related steroids failed to influence tyrosinase activity when added to the medium of proliferating cultures. Imidazole (10 mM), on the other hand, induced the activity of that enzyme 3-fold, as reported previously. Estradiol and estriol blocked imidazole induction, however, unlike the other estrogenic compounds. The blockade occurred within 15 min of hormone addition and was reversible. Dose-response studies revealed that the maximal estradiol effect occurred at 0.75 nM and the half-maximal effect occurred at 0.5 nM. Estriol was more potent, with the maximal blockade occurring at approximately 0.5 nM and half-maximal effect at 0.25 nM. The induction of tyrosinase by imidazole and the blockade of this induction by estradiol and estriol could not be demonstrated in broken cell preparations, suggesting that direct enzyme activation-inactivation was not involved. Studies utilizing inhibitors of protein and RNA synthesis suggest that this effect is mediated at a pre-translational level and is independent of mRNA destabilization.