Androgenic deficiency in male rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin

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Abstract

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the male reproductive system were investigated. Sexually mature (290 g) Sprague-Dawley rats were given single oral doses of TCDD sufficient to cause varying degrees of hypophagia and impaired body weight gain. The largest doses decreased plasma testosterone and dihydrotestosterone concentrations by 90 and 75%, respectively, from ad libitum-fed control values, while decreasing seminal vesicle and ventral prostate weights by 68 and 48%. On Day 7, the approximate ED50 for these responses was 15 μg TCDD/kg, a nonlethal dose. Reductions in caput epididymis and testis weights were also observed. The androgenic deficiency was seen as early as 2 days after dosing and persisted for at least 12 days. Based on data from pair-fed control rats, only about half the decreases in accessory sex organ weights and in plasma androgen concentrations could be accounted for by TCDD-induced hypophagia or body weight loss. These signs of androgenic deficiency were not the result of stress (based in part on plasma corticosterone assays), nor could they be accounted for by the known effects of TCDD on steroid metabolism. While the TCDD-induced depression in plasma testosterone concentrations appears to be the primary event observed, the mechanism by which testosterone concentrations were decreased remains unknown. The androgenic deficiency may account for the male reproductive pathology and dysfunction in animals treated with overtly toxic doses of TCDD.

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    Supported by USPHS Grant ES-01332, and by a grant from the University of Wisconsin Sea Grant College Program. Publication number 24-022 of the Wisconsin Regional Primate Research Center, supported by NIH Grant RR-00167. Portions of this research were presented at meetings of the Federation of American Societies for Experimental Biology (Fed. Proc. 42, 355 1983), and of the Society of Toxicology (Toxicologist 4, 187 1984).

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    Supported by PHS National Research Service Award 5-T32-ES-07015.

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