Fetal Ethanol Exposure: Hypothalamic‐Pituitary‐Adrenal and β‐Endorphin Responses to Repeated Stress

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Abstract
Previous studies provide evidence that fetal ethanol exposure induces hypothalamic-pituitary-adrenal (HPA) and pituitary β-endorphin (β-EP) hyperresponsiveness to acute stressors. The present study demonstrates significant effects of in utero ethanol exposure on the parallel response patterns of the HPA axis and the pituitary β-EP system to repeated exposures to a stressor, restraint stress, and indicates sex differences in response. Together, data from the two experiments indicate that, after repeated restraint exposures, fetal ethanol-exposed (E) males and females both show significantly increased plasma levels of adrenocorticotropin (ACTH), and E males also show significantly increased plasma levels of β-endorphin-like immunoreactivity (β-EPLIR), compared with their respective pair-fed and control counterparts. Marginal increases in the corticosterone response of E males and the β-EPLIR response of E females, compared with their controls, were also observed. In addition, delayed or deficient habituation to restraint stress was observed in the β-EPUR response of E males and the ACTH response of E females. These data demonstrate that fetal E-exposed males and females both exhibit hormonal hyperresponsiveness and/or deficits in recovery after repeated exposures to restraint stress, but that the patterns of response may differ depending on the number and duration of restraint exposures, the time course measured, and whether the endpoint measured is corticosterone, ACTH, or β-EPLIR. In addition, the finding that E and pair-fed animals both differed from their respective controls in certain developmental and hormonal measures suggests that prenatal nutritional factors may play a role in mediating some of the changes that are observed.