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1333037 
Journal Article 
Di(N-Butyl) Phthalate Rapidly Represses Steroidogenesis In The Fetal Testis And Interferes With Adrenal Steroidogenesis Through An Alternative Mechanism 
Thompson, C; Ross, SM; Heinze, S; Gaido, KW 
2004 
1 
Toxicologist
ISSN: 0731-9193 
TOX/4001181 
78 
1-S 
English 
The phthalate ester di(n-butyl) phthalate (DBP) produces antiandrogenic effects on reproductive development in male rats by interfering with testosterone production. We have shown that several genes involved in steroidogenesis are downregulated in the fetal testis following in utero exposure to DBP. Expression of these genes returns to control levels within 48 hours of DBP withdrawal. Our aim was to determine how rapidly testosterone synthesis is affected following exposure to DBP. Also, since several genes repressed by DBP are expressed in other steroidogenic tissues, we evaluated the effects of DBP exposure on steroidogenesis in the fetal adrenal. Pregnant Sprague-Dawley rats were dosed via oral gavage with 500 mg/kg/day DBP or corn oil from gestational day (gd) 12 to 19. The start of DBP dosing was shifted from gd 12 one day later in gestation for each treatment group, so that the final group was dosed only on gd 19. On gd 19, testes were removed for testosterone, RNA, and protein isolation. Testosterone production was significantly repressed in all groups exposed to DBP. The mean testosterone concentration in the fetuses dosed only on gd 19 was 44% of control. Mean testosterone concentration of all other dose groups was 13% of control. mRNA and protein levels for StAR, SR-B1, P450SCC, and CYP17 were correspondingly repressed at all time points. In the adrenal gland, corticosterone content was decreased 42% in male fetuses and 48% in female fetuses following DBP treatment from gd 12-19, although only the decrease observed in the females was statistically significant. mRNA expression of SR-B1, StAR, and P450SCC were not significantly altered in the adrenal following DBP treatment. Our results show that DBP rapidly leads to transcriptional repression in the fetal testis resulting in diminished testosterone production. Diminution of steroid concentrations in the fetal adrenal occurs through a mechanism distinct from the transcriptional repression caused by DBP in the fetal testis.