IN-UTERO AND LACTATIONAL EXPOSURE OF THE MALE-RAT TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN - IMPAIRED PROSTATE GROWTH AND DEVELOPMENT WITHOUTINHIBITED ANDROGEN PRODUCTION

To determine whether in utero and lactational 2,3,7,8-tetrachlorodiben zo-p-dioxin (TCDD) exposure decreases male rat accessory sex organ wei ghts during postnatal development secondary to decreases in testicular androgen production or changes in peripheral androgen metabolism, pre gnant Holtzman rats were administered a single dose of TCDD (1.0 mu g/ kg, po) or vehicle on Gestation Day 15 and offspring were exposed via placental and subsequent lactational transfer until weaning on Postnat al Day (PND) 21. Between PNDs 21 and 63, circulating androgen concentr ations and intratesticular androgen content tended to be decreased by in utero and lactational TCDD exposure, but in most cases decreases we re not statistically significant. In vitro human chorionic gonadotropi n-stimulated testosterone production by decapsulated testes from TCDD- exposed animals was not different from control, although S alpha-andro stane-3 alpha,17 beta-diol production was decreased on PNDs 32 and 49 and increased on PND 63. Taken together, these results imply that in u tero and lactational TCDD exposure can cause subtle decreases in testi cular androgen production. However, the biological relevance of these reductions is equivocal because they do not correlate temporally with one another or with decreases in androgen-dependent male accessory sex organ weights. Of the male accessory sex organs, ventral prostate (VP ) and dorsolateral prostate (DLP) were the most severely affected. Bet ween PNDs 21 and 63, relative VP and DLP weights were decreased to 65- 84% and 57-80% of control, respectively, and the magnitude of observed decreases was greatest at early times. In contrast, relative weights of the seminal vesicle and coagulating gland ranged from 80 to 104% of control, and the magnitude of observed decreases was greatest at late r times. The sensitivity of the prostate to TCDD could not be explaine d by tissue-specific decreases in dihydrotestosterone (DHT) concentrat ions. Although VP DHT concentration was decreased to 63% of control on PND 21, DHT concentration was not decreased in the VP between PNDs 32 and 63 or in the DLP at any time. We conclude that in utero and lacta tional TCDD exposure selectively impairs rat prostate growth and devel opment without inhibiting testicular androgen production or consistent ly decreasing prostate DHT concentration. (C) 1995 Academic Press, Inc .