Modification of Basal and Dexamethasone-Induced Suppression of Corticosterone Levels in Female Offspring Exposed to Maternal Lead Exposure, Maternal Stress or the Combination.

M. VIRGOLINI1; A. ROSSI-GEORGE1; R. LISEK1; D. WESTON1; D CORY-SLECHTA

Charlotte, North Carolina, USA.

Congreso; Society of Toxicology. 46th Annual Meeting; 2007

Society of Toxicology.

Prior experimental studies from our laboratory demonstrate that maternal Pb exposure permanently alters basal and stress-induced corticosterone levels in both male and female offspring. To evaluate the role of negative feedback inhibition of corticosterone as a mechanism of these effects, the ability of the synthetic glucocorticoid dexamethasone (DEX) to suppress corticosterone levels (DEX suppression test, 0, 10 or 15 mg/100g i.p.) over time was examined in adult female offspring subjected to either maternal Pb exposure (0, 50 or 150 ppm initiated 2 mos prior to breeding and continuing through lactation; corresponding mean blood Pbs of <2, 12 and 30 ug/dl, respectively), maternal restraint stress (45 min restraint, 3x per day on gestational days 16-17) or both. Maternal Pb alone notably delayed the post-injection reduction in corticosterone. Maternal stress interacted with maternal Pb exposure. Specifically, in controls, maternal stress delayed the post-injection reduction in corticosterone, but the blunting of the corticosterone response by DEX was equivalent in both normal and maternal stress offspring, with dose-related reductions peaking 4 hrs post DEX and returning to control levels at 8 hr. In contrast, DEX suppression showed a blunted pattern in response to combined maternal Pb and maternal stress at all 3 time points post-injection, particularly at 50 ppm. Thus, both maternal Pb and maternal stress alone reduce negative feedback inhibition in the HPA axis, and combined maternal Pb and maternal stress increases resistantance to control of corticosterone feedback. Given that DEX appears to be mediated by its actions on the pituitary, these findings suggest a peripheral mode of action of Pb that can impact CNS functions. ES012712.