Bisphenol-A imprinting of GH-dependent sexually dimorphic liver proteins and genes in female rats.

BOURGUIGNON N S; RAMIREZ MC; BONAVENTURA MM; LUX LANTOS V; LIBERTUN C; BECU-VILLALOBOS D

Houston

Congreso; The Endocrine Society's 94th Annual Meeting; 2012

The Endocrine Society (USA).

Bisphenol A (BPA) is a known endocrine disruptor that is prevalent in our environment. As an estrogenic chemical, it has potential adverse effects on animals and humans exposed during embryonic developmental stage. In a previous work we demonstrated organizational effects of neonatal steroids on the GHRH-GH axis, and sexually dimorphic GH-dependent liver enzymes in females. While most studies on the effect of neonatal exposure to BPA have concentrated on the disruption of the reproductive axis, we test the hypothesis that GH imprinting of sexually dimorphic liver enzymes is also perturbed by neonatal BPA in female rats. On postnatal days 1-10, female pups received a daily sc. injection of BPA in castor oil 50 μg/50 μL (BPA50); 500 μg/50 μL (BPA500) or vehicle. Males were injected with castor oil. Rats were studied at 4 months of age. Serum IGF-I levels were not modified by neonatal BPA treatment, but pituitary GH concentration was higher in males compared to females (P=0.039) and not different from BPA treated females (P=0.11 and 0.46 males vs. BPA500 and 50, respectively). Liver IGF-I content, a downstream target of GH, was also higher in males compared to females (P=0.039), but not to BPA500 and 50 females (P=0.987 and P=0.259, respectively). We confirmed male specific liver expression of CYP2C11 mRNA levels, with a male/female ratio of 353. BPA treatment did not masculinize its expression in females. CYP2C12 mRNA was expressed predominantly in female rat livers (female/male ratio was 53). Neonatal BPA treatment induced a partial defeminization of this gene in female livers, as BPA50 and 500 females had significant different CYP2C12 mRNA levels from both males and females (P