Dioxin-induced fetal growth retardation: the role of a preceding attenuation in the circulating level of glucocorticoid.
Exposure of pregnant rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at a low dose causes developmental disorders such as growth retardation and sexual immaturity in their pups. Our previous studies have demonstrated that TCDD attenuates the expression of pituitary luteinizing hormone in fetuses, resulting in the impairment of sexual behavior after they reach maturity. In this study, we focused on growth disturbance and investigated whether TCDD affects the expression of growth hormone (GH), another pituitary hormone which is essential for normal development in perinatal pups. The result showed that maternal exposure to TCDD (1 µg/kg) at gestational day (GD) 15 reduced the fetal expression of GH from the onset at GD18. In accordance with this, TCDD attenuated the pup weight during the perinatal period. We then examined the effect of TCDD on the serum concentration of corticosterone, which plays a key role in the proliferation of GH-producing cells, and found that TCDD reduces the circulating level of corticosterone in the mothers at GD18 and the male fetuses at GD19. The reduction in fetuses seems to be due to increased inactivation rather than reduced synthesis, because TCDD induces the fetal expression of hepatic enzymes participating in the metabolism of glucocorticoids without changing the expression of steroidogenic proteins in the pituitary-adrenal axis. Supplying corticosterone to TCDD-exposed mothers restored or tended to restore a TCDD-induced reduction in pup weight as well as the levels of pituitary GH mRNA and serum GH. These results suggest that TCDD lowers GH expression and growth retardation owing, at least partially, to a reduction in the circulating level of glucocorticoid in pregnant mothers and their fetuses.
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Yukiko
Y
Hattori
Tomoki
T
Takeda
Misaki
M
Fujii
Junki
J
Taura
Yuji
Y
Ishii
Hideyuki
H
Yamada
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D000831:Animals, Newborn; D003345:Corticosterone / Q000097:blood*; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced* / Q000378:metabolism; D005333:Fetus / Q000187:drug effects*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D010902:Pituitary Gland / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D000072317:Polychlorinated Dibenzodioxins; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D003345:Corticosterone