Modulation of growth axis gene expression by in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the weaning Holtzman rat

Abstract

While thein utero and lactational effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on both male and female reproductive systems appear to be severe, little is known about its effects on the developing growth axis. The objective of this study was to describe changes in growth axis gene expression that accompany exposure to TCDD duringin utero and lactational development. Pregnant Holtzman rats were administered 1 μg TCDD/kg maternal body weight or vehicle control on gestational day 15 by gavage. Using ribonuclease protection assays, we compared mRNA levels measured in 21-d-old female pups exposed to TCDD with levels measured in control animals for the following genes: somatostatin, growth hormone-releasing hormone (GHRH), hypothalamic and pituitary galanin (GAL), growth hormone (GH), and insulin-like growth factor-I (IGF-I). Serum GH concentrations measured by radio-immunoassay were significantly increased, although GH mRNA levels were unchanged from controls by TCDD exposure. Hypothalamic GAL mRNA was decreased in TCDD-treated animals, whereas pituitary GAL mRNA in TCDD-treated animals was not altered. GHRH mRNA was increased in hypothalami from TCDD-exposed animals. IGF-I mRNA in the liver was decreased to 67% of controls. These data indicate that the growth axis is sensitive to the effects of TCDD delivered during critical periods of development. The alterations observed in growth axis gene expression with exposure to TCDD add to the body of data demonstrating a potent effect of this compound on the fetal and neonatal endocrine system.