Acinar zonation of the hormonal regulation of cytosolic aspartate aminotransferase in the liver.

The zonation of the expression and regulation of the cytosolic aspartate aminotransferase (cAspAT) mRNAs in the liver acinus was investigated in diabetic and/or adrenalectomized rats. Dexamethasone increased cAspAT activity two- to threefold alone and up to sixfold in combination with streptozotocin-induced diabetes. Northern blot analysis showed that the cAspAT mRNAs were increased by those treatments; the effect of streptozotocin was reversed by the administration of insulin. In situ hybridization experiments showed that basal cAspAT mRNAs were uniformly distributed within the liver acinus. However, cAspAT mRNAs were induced by glucocorticoids specifically in the periportal zone and by streptozotocin in a larger area including the periportal and intermediary zone. The alpha 2u-globulin mRNAs which are specifically expressed in the perivenous hepatocytes are also induced by glucocorticoids in this zone, suggesting that the specific regulation of the cAspAT gene by glucocorticoids in the periportal zone is not due to the absence of functional glucocorticoid receptors in the other zones. We conclude that the regulation of the cAspAT housekeeping gene is zone specific in the liver. Furthermore, this zonation depends on the gene and on the type of hormonal or pharmacological treatment.