Decreased serum testosterone levels associated with 17ß-hydroxysteroid dehydrogenase activity in 7-year-old children from a dioxin-exposed area of Vietnam.

Since 2008, we have conducted epidemiological cohort studies on the relationship between dioxin exposure and disruption with children in the area sprayed with defoliants during the Vietnam War. In a long-term survey of children through the age of five, we observed androgen disruption due to decreased dehydroepiandrosterone (DHEA) and testosterone levels. In this study of 7-year-old, we separately elucidated androgen disruption for boys and girls, and discussed with respect to hormone disruption with sex differences on the steroid hormone biosynthesis process. This follow-up was conducted with 96 mother-child pairs in Vietnam (hotspot area: 45, non-sprayed area: 51). We took a questionnaire, the physical measurement and assayed 7 steroid hormones in their serum by LC-MS/MS. We examined the relationship between the hormone levels in the serum and dioxin levels in the maternal breast milk. The results showed that the serum DHEA level in the 7-year-old children in the hotspot recovered to levels in the non-sprayed area. The testosterone level of 66.5 pg/mL for boys in the non-sprayed area was 1.5 times the girls level of 44.6 pg/mL, a male-dominant effect. The testosterone level in boys and girls from the hotspot were significantly lower than in the non-sprayed area with no sex difference. The 17ß-hydroxysteroid dehydrogenase (17ß-HSD) activity was significantly higher in boys than in the girls from the non-sprayed area, but was significantly lower in the hotspot boys than in the non-sprayed area boys. Both the testosterone level and 17ß-HSD activity in the boys were inversely correlated with the TEQ total PCDD/Fs in the maternal breast milk. These results indicated that dioxin delayed the expression of the testosterone level and 17ß-HSD activity with growth in the 7-year-old boys. The serum DHEA in the 7-year-old children recovered to the levels of the children in the non-sprayed area.

Androgen disruption by dioxin exposure in 5-year-old Vietnamese children: Decrease in serum testosterone level.

Dioxins have been suspected to be potential substances causing endocrine disruptions in humans. We are conducting the research in one of three dioxin exposure areas (hotspots) in Vietnam. We previously reported that the salivary dehydroepiandrosterone (DHEA) level decreased in 3-year-old Vietnamese children and that it was significantly inversely correlated with polychlorinated dibenzodioxin/dibenzofuran levels in their mother's breast milk. In this study, we investigated the influence of exposure to dioxin on steroid hormone biosynthesis in the same children when they reached 5 years of age, focusing on androgens. Thirty-five and 50 mother-child pairs from dioxin hotspot and non-sprayed areas, respectively, participated in this study. Maternal breast milk was donated at 4 to 16 weeks postpartum in 2008 to measure dioxin levels by gas chromatography/high-resolution mass spectrometry. Serum was collected from 5-year-old children in 2013. Seven steroid hormones were measured by liquid chromatography/mass spectrometry. Most dioxin congeners in breast milk were 2- to 10-fold higher in the hotspot than in the non-sprayed area. DHEA and testosterone (T) were significantly lower in the hotspot and showed negative correlations with most dioxin congeners. Similar results were observed for the activities of cytochrome P450-17, 20 lyase (CYP17 lyase), and 17ß-hydroxysteroid dehydrogenase (HSD). Conversely, the elevated androstenedione (A-dione) level and 3ß-HSD activity in children from the hotspot were positively correlated with dioxin levels. Moreover, a positive correlation was shown between T and 17ß-HSD. It is possible that dioxin inhibits 17ß-HSD activity, leading to a decrease in the T level. Multiple regression analysis indicated that dioxin had a strong association with the DHEA, A-dione, and T levels. In conclusion, the present study suggests that dioxin is associated with low levels of DHEA and T and inhibition of the activity of steroidogenic enzymes such as CYP17 lyase and 17ß-HSD in 5-year-old children.