Chronic effects of diethylstilbestrol on estrogen metabolism in the mouse

Female C3H mice were exposed to 0 (control) and 640 ppb DES (experimental) in the diet for 12 mon. Subsequently, both groups of animals were dosed orally with radiolabeled 3H-DES. Experimental animals received low (349 ng) and high (312 micrograms) doses while controls received low doses. Based on the total plasma radioactivity derived from 3H-DES, comparisons of the apparent volume of distribution (AVD), metabolic clearance rate (MCR) and the plasma half-life (T1/2) were made. The AVD's and MCR's calculated for both experimental groups were significantly less than the control group (P less than 0.05). However, the T1/2's did not differ between experimental and control groups. Metabolic studies with 14C-DES (312 micrograms) showed that control and experimental animals differed only in their urinary-conjugate patterns. Pharmacokinetic studies with intravenously administered 3H-estradiol (E2) were performed in control mice, 640 ppb DES fed mice and 5000 ppb E2 fed mice. Significant differences were observed (P less than 0.005) between the experimental and control groups with regard to plasma T1/2, but not AVD or MCR. These results indicate that chronic estrogen exposure alters some pharmacokinetic properties of both steroidal and non-steroidal estrogens.