Estrogenic modulation of CYP3A38, CYP3A40, and CYP19 in mature male medaka (Oryzias latipes)

Shosaku Kashiwada, Maiko Kameshiro, Haruki Tatsuta, Yoshio Sugaya, Seth W. Kullman, David E. Hinton, Koichi Goka

研究成果: Contribution to journalArticle査読

23 被引用数 (Scopus)


We examined cytochrome P450 production and activity and circulating hormone concentrations in male medaka exposed to 17β-estradiol (E2) or 17α-ethinylestradiol (EE2). Intraperitoneal injection of E2 at 1, 10, or 100 μg/g-fish completely suppressed CYP3A38 protein production and suppressed CYP3A40 protein levels by 89%, 52%, or 47%, respectively. CYP3A38 and CYP3A40 mRNA expression was unaltered, and CYP3A enzymatic activity initially increased and then decreased with increasing E2 dose. Males co-cultured with females were exposed to a markedly high concentration (43 ng/L) of E2 secreted by females. CYP3A protein levels in co-cultured males were suppressed. Serum testosterone (TE) and 11keto-testosterone levels in co-cultured males were downregulated to 40% of pre-exposure levels. Serum E2 levels increased in co-cultured males or males exposed to EE2. Testicular CYP19, which converts TE to E2, increased by 9.5 times in males exposed to 50 ng/L EE2 and by 21.5 times in those exposed to 100 ng/L EE2. Male medaka exposed to EE2 showed increased serum Vtg levels. Estrogenic exposure induced Vtg production, suppressed CYP3A protein production, downregulated TE metabolism, and enhanced CYP19 activity. Serum E2 endogenously induced by CYP19 could contribute to Vtg induction in male medaka.

ジャーナルComparative Biochemistry and Physiology - C Toxicology and Pharmacology
出版ステータス出版済み - 4 2007

All Science Journal Classification (ASJC) codes

  • 生化学
  • 生理学
  • 毒物学
  • 細胞生物学
  • 健康、毒物学および変異誘発


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