Przybycien-Szymanska MM, Rao YS, Pak TR. Binge-pattern alcohol exposure during puberty induces sexually dimorphic changes in genes regulating the HPA axis. Am J Physiol Endocrinol Metab 298: E320 -E328, 2010. First published December 1, 2009; doi:10.1152/ajpendo.00615.2009.-Maternal alcohol consumption during critical periods of fetal brain development leads to devastating long-term consequences on adult reproductive physiology, cognitive function, and social behaviors. However, very little is known about the long-term consequences of alcohol consumption during puberty, which is perhaps an equally dynamic and critical period of brain development. Alcohol abuse during adulthood has been linked with an increase in clinically diagnosed anxiety disorders, yet the etiology and neurochemical mechanisms of alcohol-induced anxiety behavior is unknown. In this study, we determined the effects of binge ethanol exposure during puberty on two critical central regulators of stress and anxiety behavior: corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP). Our results showed that ethanol increased plasma corticosterone (CORT) levels in both sexes, yet binge-treated animals had significantly lower CORT levels than animals exposed to a single dose, suggesting that the hypothalamo-pituitary-adrenal (HPA) axis habituated to the repeated stressful stimuli of ethanol. Binge ethanol exposure also significantly increased CRH and AVP gene expression in the paraventricular nucleus of males, but not females. Overall, our results demonstrate that binge ethanol exposure during puberty changes the central expression of stress-related genes in a sex-specific manner, potentially leading to permanent dysregulation of the HPA axis and long-term behavioral consequences.hypothalamus; puberty; arginine vasopressin; corticotrophin-releasing hormone; corticosterone; hypothalamo-pituitary-adrenal axis ALCOHOL ABUSE DURING ADOLESCENCE is a growing fundamental heath concern in the United States. According to the US Department of Health and Human Services, boys on average have had their first drink before age 11, and girls before age 13, with the overall statistics showing that 41% of teenagers have had their first drink by age 14. Underage drinkers typically adopt a "binge" pattern of alcohol consumption, defined by the National Institute on Alcohol Abuse and Alcoholism as heavy, episodic drinking in which enough alcohol is consumed in one sitting to bring the blood alcohol concentration (BAC) Ͼ0.08 g/100 g (55). During adolescence, significant neural remodeling occurs as evidenced by changes in cortical gray matter (22,29,37), neurogenesis (40), and increased synaptic connectivity (14,49,57), raising the possibility that alcohol consumption during this critical period can lead to long-term neurobiological and behavioral defects.One neurological system that undergoes extensive plasticity during pubertal development is the hypothalamo-pituitaryadrenal (HPA) axis (46). Under normal physiological conditions, an acute psychological or ph...