Alterations in the urine excretion of estrogen metabolites in breast cancer women treated with aminoglutethimide.
The effect of aminoglutethimide treatment on urine estrogen glucuronide excretion was investigated using injections of [4-14C]estradiol (4 women) or [4-14C]estrone (2 women). Each patient received 25 mu Ci of either [4-14C]estradiol or [4-14C]estrone as a bolus injection before initiation of aminoglutethimide treatment, and an equal injection following 3-20 weeks on treatment with aminoglutethimide 250 mg q.i.d. with hydrocortisone (50 mg b.i.d. for 2 weeks, then 25 mg b.i.d.). Urine was collected for 24-72 h following each injection. Aminoglutethimide treatment caused significant alterations in the metabolite profiles of estradiol and estrone but with large interindividual variations. [14C]Estriol glucuronide excretion was increased by a median value of 48.6%. [14C]16 alpha-Hydroxyestrone glucuronide and [14C]16-epi-estriol glucuronide excretion was increased by median values of 16.3 and 37.7% respectively, and [14C]2-hydroxyestriol glucuronide excretion was increased by a median value of 115.9%. Contrary, excretion of the catechol estrogen glucuronides (2- and 4-hydroxylated metabolites) were reduced (mean reduction of 14.8 and 67.3% respectively). The amount of urine radioactivity excreted as [14C]estradiol and [14C]estrone glucuronide were consistently reduced by aminoglutethimide treatment (median reduction of 36.8 and 38.2% respectively). These findings suggest aminoglutethimide to stimulate the estrone 16 alpha-hydroxylase and possibly the estrone 16 beta-hydroxylase located in the hepatic endoplasmic reticulum.
Lønning
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PE
Department of Biochemical Endocrinology, University of Bergen, Norway.
Skulstad
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D000328:Adult; D000368:Aged; D000616:Aminoglutethimide / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004967:Estrogens / Q000652:urine*; D005260:Female; D006801:Humans; D008875:Middle Aged; D039181:Steroid 16-alpha-Hydroxylase; D013963:Thyroid Hormones / Q000097:blood
D004967:Estrogens; D013963:Thyroid Hormones; D000616:Aminoglutethimide; D039181:Steroid 16-alpha-Hydroxylase