Kato R, Yamazoe Y, Shimada M, Murayama N, Kamataki T
J Biochem. 1986 Oct;100(4):895-902. doi: 10.1093/oxfordjournals.jbchem.a121802.
The effects of growth hormone and ectopic transplantation of pituitary gland on the amounts of sex-specific cytochrome P-450, P-450-male and P-450-female, and the activities of testosterone and drug hydroxylases in male rat liver microsomes were studied. Hypophysectomy decreased the content of P-450-male, without changing the total cytochrome P-450 level. The continuous infusion of growth hormone into hypophysectomized rats and the transplantation of pituitary gland under the renal capsule caused a further decrease in P-450-male content and an expression of P-450-female. In contrast, the intermittent injection of growth hormone into hypophysectomized rats increased P-450-male content to the level seen in intact male rats. The activities of testosterone 2 alpha- and 16 alpha-, but not 6 beta-, 7 alpha-, or 15 alpha-hydroxylase, were changed in association with the level of P-450-male by these treatments. Anti-P-450-male immunoglobulin G inhibited testosterone 2 alpha- and 16 alpha-hydroxylations, but not 6 beta-, 7 alpha- or 15 alpha-hydroxylation. These results indicate that growth hormone regulates the expression of P-450-male responsible for testosterone 2 alpha- and 16 alpha-hydroxylations. The metabolism of 7-propoxycoumarin, benzo(a)pyrene and aminopyrine also changed with the content of P-450-male, although the correlation was less than that observed with testosterone 2 alpha- and 16 alpha-hydroxylation.
研究了生长激素和垂体异位移植对雄性大鼠肝微粒体中性别特异性细胞色素P-450、P-450-雄性和P-450-雌性的含量以及睾酮和药物羟化酶活性的影响。垂体切除降低了P-450-雄性的含量,而总细胞色素P-450水平未发生变化。向垂体切除的大鼠持续输注生长激素以及将垂体移植到肾被膜下导致P-450-雄性含量进一步降低并出现P-450-雌性的表达。相反,向垂体切除的大鼠间歇性注射生长激素可使P-450-雄性含量增加至完整雄性大鼠的水平。通过这些处理,睾酮2α-和16α-羟化酶的活性发生改变,而6β-、7α-或15α-羟化酶的活性未改变,且这些改变与P-450-雄性的水平相关。抗P-450-雄性免疫球蛋白G抑制睾酮2α-和16α-羟化,但不抑制6β-、7α-或15α-羟化。这些结果表明,生长激素调节负责睾酮2α-和16α-羟化的P-450-雄性的表达。尽管7-丙氧基香豆素、苯并(a)芘和氨基比林的代谢与P-450-雄性含量的相关性小于睾酮2α-和16α-羟化的相关性,但它们的代谢也随P-450-雄性的含量而改变。