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持续输注给予的正常和重组人生长激素使大鼠肝微粒体的儿茶酚雌激素形成女性化。

Normal and recombinant human growth hormone administered by constant infusion feminize catechol estrogen formation by rat liver microsomes.

作者信息

Jellinck P H, Quail J A, Crowley C A

出版信息

Endocrinology. 1985 Dec;117(6):2274-8. doi: 10.1210/endo-117-6-2274.

DOI:10.1210/endo-117-6-2274
PMID:2998732
Abstract

Human GH or recombinant DNA-derived human GH administered to normal mature male rats by constant infusion decreased hepatic 2-hydroxylation of estradiol to female levels, as measured by 3H2O release and isolation of the catechol estrogen product. PRL had no effect under the same conditions. The maximum response to GH was attained at an infusion rate of 0.02 IU/h . kg after 5-7 days, and a significant change was observed within 1-2 days. The effect of GH was primarily on hydroxylation of C-2 of the estrogen, as demonstrated by comparative studies with estradiol labeled with 3H at C-4 or C-6,7, and appeared to be mediated by the cytochrome P-450 system of the liver microsomes. Ascorbic acid at 1 mM did not affect 2-hydroxylation significantly while protecting the catechol estrogen produced from further oxidation. The results indicate that GH has the potential to regulate estrogen metabolism in the liver and provide evidence for another component in the hypothalamic-pituitary-liver axis.

摘要

通过持续输注向正常成熟雄性大鼠给药人生长激素(GH)或重组DNA衍生的人GH,可将雌二醇的肝脏2-羟化作用降低至雌性水平,这是通过3H2O释放和儿茶酚雌激素产物的分离来测定的。在相同条件下,催乳素(PRL)没有影响。在5-7天后,以0.02 IU/h·kg的输注速率可达到对GH的最大反应,并且在1-2天内观察到显著变化。与在C-4或C-6、7处用3H标记的雌二醇进行的比较研究表明,GH的作用主要是对雌激素C-2的羟化作用,并且似乎是由肝微粒体的细胞色素P-450系统介导的。1 mM的抗坏血酸在保护产生的儿茶酚雌激素不被进一步氧化的同时,对2-羟化作用没有显著影响。结果表明,GH有调节肝脏中雌激素代谢的潜力,并为下丘脑-垂体-肝脏轴中的另一个组成部分提供了证据。

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引用本文的文献

1
Growth hormone: roles in male reproduction.生长激素:在男性生殖中的作用。
Endocrine. 2000 Dec;13(3):243-50. doi: 10.1385/ENDO:13:3:243.
2
Downregulation of the male-specific hepatic microsomal steroid 16 alpha-hydroxylase, cytochrome P-450UT-A, in rats with portal bypass. Relevance to estradiol accumulation and impaired drug metabolism in hepatic cirrhosis.门静脉分流大鼠中雄性特异性肝微粒体类固醇16α-羟化酶细胞色素P-450UT-A的下调。与肝硬化中雌二醇蓄积及药物代谢受损的相关性。
J Clin Invest. 1989 Apr;83(4):1211-6. doi: 10.1172/JCI114003.