Bender D A, Laing A E, Vale J A, Papadaki L, Pugh M
Biochem Pharmacol. 1983 Mar 1;32(5):843-8. doi: 10.1016/0006-2952(83)90586-5.
The effects of the administration of oestrogens on the activity of hepatic tryptophan oxygenase have been assessed both directly (by measurement of enzyme activity in vitro) and indirectly (by measurement of urinary excretion of tryptophan metabolites) in rats, and indirectly in menopausal women receiving hormone replacement therapy. Intraperitoneal administration of 500 micrograms of oestradiol or ethinyl oestradiol/kg body wt had no effect on the activity of tryptophan oxygenase in homogenates of liver from mature (13-week-old) female rats. Both adrenalectomy and ovariectomy led to a reduction in the activity of tryptophan oxygenase in homogenates of liver from mature rats; again there was no effect of giving 500 micrograms of oestradiol/kg body wt by intraperitoneal injection. Intraperitoneal administration of 210 micrograms of oestrone sulphate/kg body wt for 1 or 2 days before killing, or its incorporation in the diet for up to 8 weeks at an equivalent dose rate, had no effect on the activity of tryptophan oxygenase in homogenates of liver from ovariectomized 6-14-week-old female rats. Intraperitoneal administration of 500 micrograms oestradiol/kg body wt to intact mature female rats together with 500 mg tryptophan/kg body wt caused a reduction in the urinary excretion of xanthurenic and kynurenic acids, kynurenine and N1-methyl nicotinamide. When peri- and post-menopausal women were treated with ethinyl oestradiol (20 micrograms/day) or piperazine oestrone sulphate (3 mg/day) for 3 months, there was an increase in the concn of tryptophan in plasma, with no change in the urinary excretion of xanthurenic and kynurenic acids and kynurenine. This study provides no evidence for the induction of tryptophan oxygenase by oestrogens in rats or human beings.
已通过直接(通过体外测量酶活性)和间接(通过测量色氨酸代谢产物的尿排泄量)两种方式评估了雌激素给药对大鼠肝脏色氨酸加氧酶活性的影响,并对接受激素替代疗法的绝经后女性进行了间接评估。给成熟(13周龄)雌性大鼠腹腔注射500微克/千克体重的雌二醇或炔雌醇对肝脏匀浆中色氨酸加氧酶的活性没有影响。肾上腺切除术和卵巢切除术均导致成熟大鼠肝脏匀浆中色氨酸加氧酶的活性降低;再次腹腔注射500微克/千克体重的雌二醇也没有效果。在处死前1天或2天给去卵巢的6至14周龄雌性大鼠腹腔注射210微克/千克体重的硫酸雌酮,或以等效剂量率将其掺入饮食中长达8周,对肝脏匀浆中色氨酸加氧酶的活性没有影响。给完整的成熟雌性大鼠腹腔注射500微克/千克体重的雌二醇并同时注射500毫克/千克体重的色氨酸,会导致尿中黄尿酸、犬尿酸、犬尿氨酸和N1-甲基烟酰胺的排泄量减少。当围绝经期和绝经后女性用炔雌醇(20微克/天)或哌嗪硫酸雌酮(3毫克/天)治疗3个月时,血浆中色氨酸浓度升高,而尿中黄尿酸、犬尿酸和犬尿氨酸的排泄量没有变化。这项研究没有提供证据表明雌激素能在大鼠或人类中诱导色氨酸加氧酶。