The purpose of this research is to: 1) characterize the development of specific behavioral and neural functions accompanying perturbations of the hypothalamic-pituitary- adrenal axis (HPAA), 2) determine the physiological mechanisms by which abnormalities are expressed, and 3) identify specific environmental or pharmacological treatments which can mitigate the consequences of such physiological injury. Perturbation of the HPAA with chlordecone, an organochlorine which has estrogenic-like activity, had an organizational effect on sexual differentiation of neural tissue in rats. If dosing with chlordecone occurred on day 4 neonatally, the optimal time of sexual differentiation, sexually dimorphic alterations in functional and structural measurements (body weight regulation, gross motor movements, and general motor activity) were observed, suggesting an organizational effect. Treatment with chlordecone on day 11 of age had little or no sexually dimorphic effect, indicating a lack of an activational effect. It was also confirmed that chlordecone produces a generalized activation of adrenal steroids, as determined by the presence of circulating adrenal steroids at various times after treatment and an increased adrenal weight attributable to cellular hypertrophy/hyperplasia. These effects may explain long-term changes in circulating steroids in adult animals exposed neonatally to chlordecone. These data indicate that developmental exposure to agents having steroidal activity or those that stress the neonate causing a release of steroids can have long-term effects on the HPAA at adulthood. This is the final report for this project and no further work is planned.
