Ohno Shuji, Nakajima Yonako, Inoue Koichi, Nakazawa Hiroyuki, Nakajin Shizuo
Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
Life Sci. 2003 Dec 26;74(6):733-42. doi: 10.1016/j.lfs.2003.04.006.
The phytochemical flavonoid genistein has been shown to act as a potent competitive inhibitor of human adrenocortical 3beta-hydroxysteroid dehydrogenase and cytochrome P450 21-hydroxylase activities in vitro [J. Steroid Biochem. Molec. Biol. 2002; 80: 355-363]. In the present study, we evaluated the effects of large amounts of genistein continuously administered to weanling rats, particularly on steroidogenesis at the pubertal stage in vivo. Serum concentrations of free and total genistein were significantly higher in the 40 mg/kg genistein administration group when compared with the control group. In genistein administered rats, adrenal weight was significantly higher. Furthermore, a clear expansion of cells was observed in hematoxylin and eosin stained tissue at the zona fasciculata and zona reticularis of the adrenal cortex. However in the testis, no differences in weights or histologic changes were observed. Serum corticosterone concentration significantly decreased to 50% of control levels by 40 mg/kg genistein administration and testosterone also tended to decrease with this dose of genistein. On the other hand, although serum follicle stimulating hormone was unchanged, adrenocorticotropic hormone and luteinizing hormone levels increased with genistein administration. These results suggest a significant effect of genistein on steroidogenesis in the adrenal gland and testis of rats, and this effect appeared to be more evident on steroid production in adrenals than in testis in vivo.
植物化学物质黄酮类染料木黄酮已被证明在体外可作为人肾上腺皮质3β-羟基类固醇脱氢酶和细胞色素P450 21-羟化酶活性的有效竞争性抑制剂[《类固醇生物化学与分子生物学杂志》2002年;80:355 - 363]。在本研究中,我们评估了持续给予断奶大鼠大量染料木黄酮的影响,特别是对体内青春期阶段类固醇生成的影响。与对照组相比,40毫克/千克染料木黄酮给药组的游离和总染料木黄酮血清浓度显著更高。在给予染料木黄酮的大鼠中,肾上腺重量显著更高。此外,在苏木精和伊红染色的肾上腺皮质束状带和网状带组织中观察到细胞明显扩张。然而,在睾丸中,未观察到重量或组织学变化的差异。给予40毫克/千克染料木黄酮后,血清皮质酮浓度显著降至对照水平的50%,并且睾酮也倾向于随着该剂量的染料木黄酮而降低。另一方面,虽然血清促卵泡激素没有变化,但促肾上腺皮质激素和黄体生成素水平随着染料木黄酮给药而升高。这些结果表明染料木黄酮对大鼠肾上腺和睾丸中的类固醇生成有显著影响,并且这种影响在体内对肾上腺类固醇生成的作用似乎比对睾丸更明显。