Alcoholic liver disease affects millions of people worldwide and is a major cause of morbidity and mortality. ALD encompasses varying degrees of hepatic injury progressing from steatosis to more advanced damage, including hepatic inflammation and cell death, fibrosis/cirrhosis and hepatocellular carcinoma. However, less than 10% of heavy drinkers progress to later stages of injury, suggesting other contributing factors in development of severe liver injury due to excessive alcohol consumption. Of these factors, health status, environmental exposures and genetics influence development and progression of ALD. Sex differences are observed in rodent models of ALD, with females displaying greater susceptibility to the detriments of alcohol than males. Since decreasing estrogen levels protects females from ethanol-induced liver injury, E2 is implicated in sex differences observed in ALD. However, in these reports, E2 manipulation was initiated post-pubertally or at 4 weeks of age. No studies to date have determined the contribution of cyclic E2 in the development of ALD. Additionally, OVX studies cannot exclude the possibility that other ovarian factors besides E2 may play a role in development and progression of ALD. Gonadal sex steroid hormone levels are regulated by the hypothalamic pituitary gonadal axis, which is disrupted by neonatal androgenization. Further, gonadal hormone production, regulated by the HPG axis, programs sex-specific expression of hepatic enzymes during pubertal development and can profoundly affect adult liver physiology. Perinatal hormonal imprinting of hepatic enzymes including members of the cytochrome P450 family and those involved in steroid metabolism has been shown. Alterations in expression of ethanol metabolizing enzymes have been implicated in predisposition to ALD. Following acute and chronic ethanol consumption, hepatocytes are the principal site of ethanol metabolism. Classically, ethanol metabolism occurs via alcohol dehydrogenase, the microsomal ethanol oxidizing system, comprised predominantly of BYL719 inducible cytochrome P450 2E1 and catalase. Metabolism by ADH and CYP2E1 generates reactive oxygen species, promoting lipid peroxidation, protein adduct formation and collagen synthesis, the major mechanisms of damage in ALD progression. The liver counteracts the deleterious effects of oxidative stress via increased antioxidant defense mechanisms, providing protection against ALD development. During chronic ethanol exposure, the balance between prooxidants and anti-oxidants may favor pro-oxidants, thus rendering the cell susceptible to oxidative stress. Despite increased oxidative stress by ethanol-induced CYP2E1, previous studies report CYP2E1 expression may not be the predominant mechanism of alcohol-induced damage, suggesting possible involvement of other CYP450 family members in ethanol metabolism and ALD progression. CYP1A2 is also capable of metabolizing ethanol, and interestingly, is induced in a sexspecific manner with potential regulation by E2. Therefore, sex-specific ethanol metabolizing enzymes may contribute to sexual dimorphism in ALD. In the present study, neonatal androgenization was used as a model to examine the contribution of adult cyclic E2 in the development and progression of ALD.