Effects of oral androstenedione on steroid metabolism in liver of pregnant and non-pregnant female rats

• Published in: Food and chemical toxicology Vol. 43; no. 4; pp. 537 - 542
• Main Authors: Flynn, T.J., Sapienza, P.P., Wiesenfeld, P.W., Ross, I.A., Sahu, S., Kim, C.S., O’Donnell, M.W., Collins, T.F.X., Sprando, R.L.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.04.2005; New York, NY Elsevier Science
• Subjects: Administration, Oral; adverse effects; Androstenedione; Androstenedione - administration & dosage; Androstenedione - pharmacology; Animals; Biological and medical sciences; cytochrome P-450; Cytochrome P-450 Enzyme System - pharmacology; Cytochromes P450; dosage; Endocrine disruption; endocrine-disrupting chemicals; ergogenic aids; Female; gestational age; hepatotoxicity; hormone metabolism; hormone supplements; Liver; Liver - drug effects; Liver - physiology; liver microsomes; maternal nutrition; Medical sciences; nutrient-drug interactions; Pregnancy; pregnancy outcome; pregnant women; Rats; Steroids; Steroids - metabolism; Toxicology; Endocrine disruption; Androstenedione; Liver; Steroids; Cytochromes P450; Steroid; Rat; Digestive system; Enzyme; Cytochrome P450; Rodentia; Endocrine disruptor; Metabolism; Pregnancy; Vertebrata; Mammalia; Animal; Female
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2004.12.007

It is unknown whether androstenedione, a steroidal dietary supplement taken to enhance athletic performance, can affect physiological hormone levels by altering liver enzyme activities that metabolize steroid hormones. Altered hormone levels could be especially devastating during pregnancy. Mature female rats were gavaged with 0, 5, 30 or 60 mg/kg/day androstenedione beginning two weeks prior to mating and continuing through gestation day 19. Non-pregnant female rats were gavaged over the same time frame with 0 or 60 mg/kg/day androstenedione. Livers were removed from dams on gestation day 20 and from non-pregnant rats after five weeks’ treatment. Liver microsomes were incubated with 200 μM testosterone, and the reaction products were isolated and analyzed by HPLC. In pregnant rats, formation of 6α-, 15β-, 7α-, 16β-, and 2β-hydroxytestosterone was increased significantly vs. control at the highest dose level only. Formation of 6β-hydroxytestosterone increased significantly at both the 30 and 60 mg/kg/day dose levels. In non-pregnant rats, 60 mg/kg/day androstenedione significantly increased formation of 15β-, 6β-, 16β-, and 2β-hydroxytestosterone. The data suggest that high oral doses of androstenedione can induce some female rat liver cytochromes P450 that metabolize steroid hormones and that the response to androstenedione does not differ between pregnant and non-pregnant female rats.