title: In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p-dioxin: impaired prostate growth and development without inhibited androgen production.
abstract: To determine whether in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure decreases male rat accessory sex organ weights during postnatal development secondary to decreases in testicular androgen production or changes in peripheral androgen metabolism, pregnant Holtzman rats were administered a single dose of TCDD (1.0 microgram/kg, po) or vehicle on Gestation Day 15 and offspring were exposed via placental and subsequent lactational transfer until weaning on Postnatal Day (PND) 21. Between PNDs 21 and 63, circulating androgen concentrations and intratesticular androgen content tended to be decreased by in utero and lactational TCDD exposure, but in most cases decreases were not statistically significant. In vitro human chorionic gonadotropin-stimulated testosterone production by decapsulated testes from TCDD-exposed animals was not different from control, although 5 alpha-androstane-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 utero and lactational TCDD exposure can cause subtle decreases in testicular 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. Between 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 later times. The sensitivity of the prostate to TCDD could not be explained by tissue-specific decreases in dihydrotestosterone (DHT) concentrations. 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 lactational TCDD exposure selectively impairs rat prostate growth and development without inhibiting testicular androgen production or consistently decreasing prostate DHT concentration.
authors.affiliation: Environmental Toxicology Center, University of Wisconsin, Madison 53706, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Roman
authors.forename: R J
authors.initials: RJ
authors.lastname: Sommer
authors.forename: K
authors.initials: K
authors.lastname: Shinomiya
authors.forename: R E
authors.initials: RE
authors.lastname: Peterson
mesh_terms: D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000032:analysis; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011467:Prostate / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D051381:Rats
chemical_list: D000728:Androgens; D006063:Chorionic Gonadotropin; D000072317:Polychlorinated Dibenzodioxins; D013196:Dihydrotestosterone