MODULATION OF GROWTH AXIS GENE-EXPRESSION BY IN-UTERO AND LACTATIONALEXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) IN THE WEANINGHOLTZMAN RAT

While the in utero and lactational effects of 2,3,7,8-tetrachlorodiben zo-p-dioxin (TCDD) on both male and female reproductive systems appear to be severe, little is known about its effects on the developing gro wth axis. The objective of th is study was to describe changes in grow th axis gene expression that accompany exposure to TCDD during in uter o and lactational development. Pregnant Holtzman rats were administere d 1 mu g TCDD/kg maternal body weight or vehicle control on gestationa l day 15 by gavage. Using ribonuclease protection assays, we compared mRNA levels measured in 21-d-old female pups exposed to TCDD with leve ls measured in control animals for the following genes: somatostatin, growth hormone-releasing hormone (GHRH), hypothalamic and pituitary ga lanin (GAL), growth hormone (GH), and insulin-like growth factor-I (IG F-I). Serum CH concentrations measured by radioimmunoassay were signif icantly increased, although GH mRNA levels were unchanged from control s by TCDD exposure. Hypothalamic GAL mRNA was decreased in TCDD-treate d animals, whereas pituitary GAL mRNA in TCDD-treated animals was not altered. GHRH mRNA was increased in hypothalami from TCDD-exposed anim als. IGF-I mRNA in the liver was decreased to 67% of controls. These d ata indicate that the growth axis is sensitive to the effects of TCDD delivered during critical periods of development. The alterations obse rved in growth axis gene expression with exposure to TCDD add to the b ody of data demonstrating a potent effect of this compound on the feta l and neonatal endocrine system.