期刊
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 80, 期 3, 页码 355-363出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0960-0760(02)00021-3
关键词
adrenocortical H295R cell; steroidogenesis; phytoestrogen; flavonoids; enzyme inhibition
Inhibitory effects of flavonoid phytochemicals, flavones, flavonols and isoflavones on cortisol production were examined in human adrenal H295R cells stimulated with di-buthylyl cAMP. In addition, the inhibitory effects of these chemicals on the activity of P450see, 3beta-HSD type II (3beta-HSD II), P450c 17, P450c21 and P45011beta, steroidogenic enzymes involved in cortisol biosynthesis, were examined in the same cells. Exposure to 12.5 muM of the flavonoids 6-hydroxyflavone, 4-hydroxyflavone, apigenin, daidzein, genistein and formononetin significantly decreased cortisol production (by 6.3, 69.6, 47.5, 26 6, 13.8 and 11.3%, respectively), and biochanin A significantly decreased cortisol production (by 47.3%) at a concentration of 25 muM without any significant cytotoxic effects or changes in cell number. Daidzin, the 7-glucoside of daidzein, did not alter cortisol production by H295R cells at concentrations over 10 mug/ml (24 muM). Daidzein -induced reduction of cortisol production by H295R cells was not inhibited by the estrogen receptor antagonist ICI 182,780. The flavonoids 6-hydroxyflavone, daidzein, genistein, biochanin A and formononetin strongly and significantly inhibited microsomal 3beta-HSD II activity at concentrations from 1 to 25 muM, and I-50 values were estimated to be 1.3, 2, 1, 0.5 and 2.7 muM, respectively. In addition, these flavonoids significantly inhibited microsomal P450c21 activity at 12.5 and/or 25 muM. In addition, 6-hydroxyflavone inhibited activity of microsomal P450c17 and mitochondrial P45011beta at 12.5 and/or 25 muM. Results of Lineweaver-Burk's plot analysis indicate that daidzein is a competitive inhibitor of the activity of 3beta-HSDII and P450c21. K-m and V-max values of 3beta-HSDII for DHEA were estimated to be 6.6 muM and 328 pmol/min mg protein, respectively. K-m and V-max values of P450c21 for progesterone were estimated to be 2.8muM and 16 pmol/min mg protein, respectively. K-i values of 3beta-HSD It and P450c21 for daidzein were estimated to be 2.9 and 33.3 muM, respectively. (C) 2002 Elsevier Science Ltd. All rights reserved.
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