Roman B L, Sommer R J, Shinomiya K, Peterson R E
Environmental Toxicology Center, University of Wisconsin, Madison 53706, USA.
Toxicol Appl Pharmacol. 1995 Oct;134(2):241-50. doi: 10.1006/taap.1995.1190.
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.
为了确定子宫内及哺乳期暴露于2,3,7,8-四氯二苯并对二恶英（TCDD）是否会在出生后发育过程中，因睾丸雄激素生成减少或外周雄激素代谢改变，而导致雄性大鼠附属生殖器官重量减轻，在妊娠第15天给妊娠的霍尔茨曼大鼠单次经口给予一剂TCDD（1.0微克/千克）或赋形剂，其后代通过胎盘及随后的哺乳期转移暴露，直至出生后第21天断奶。在出生后第21天至63天之间，子宫内及哺乳期暴露于TCDD往往会使循环雄激素浓度和睾丸内雄激素含量降低，但在大多数情况下，降低幅度无统计学意义。尽管在出生后第32天和49天，5α-雄烷-3α,17β-二醇生成减少，而在出生后第63天增加，但TCDD暴露动物去包膜睾丸经体外人绒毛膜促性腺激素刺激后的睾酮生成与对照组并无差异。综合来看，这些结果表明子宫内及哺乳期暴露于TCDD可导致睾丸雄激素生成出现细微减少。然而，这些减少的生物学相关性并不明确，因为它们在时间上彼此之间或与雄激素依赖性雄性附属生殖器官重量的减少并无关联。在雄性附属生殖器官中，腹侧前列腺（VP）和背外侧前列腺（DLP）受影响最为严重。在出生后第21天至63天之间，VP和DLP的相对重量分别降至对照组的65 - 84%和57 - 80%，且观察到的减少幅度在早期最大。相比之下，精囊和凝固腺的相对重量为对照组的80%至104%，观察到的减少幅度在后期最大。前列腺对TCDD的敏感性无法用二氢睾酮（DHT）浓度的组织特异性降低来解释。尽管在出生后第21天，VP的DHT浓度降至对照组的63%，但在出生后第32天至63天之间，VP中的DHT浓度并未降低，且在任何时候DLP中的DHT浓度也未降低。我们得出结论，子宫内及哺乳期暴露于TCDD会选择性地损害大鼠前列腺的生长和发育，而不会抑制睾丸雄激素生成或持续降低前列腺DHT浓度。
