Modulation of hepatic and renal alcohol dehydrogenase activity and mRNA by steroid hormones in vivo.

Abstract

Alcohol dehydrogenase (ADH) catalyzes the flux-determining step in the oxidation of ethanol and probably also plays a role in the metabolism of steroid alcohols and retinoids. Five classes of ADH have been discovered to date (Ehrig et al., 1990). The class I enzyme is the major liver enzyme, which is also found in other tissues at lower levels. This class of ADH has been studied in greatest detail. The gene for class I ADH has been cloned from humans (Duester et al. 1986), mice (Zhang et al., 1987), and rats (Crabb et al., 1989). In vitro studies have identified promoter elements important for liver specific expression (C/EBP and HNF1 binding sites (Potter et al., 1991; Stewart et al., 1990a; Stewart et al., 1990b; Stewart et al., 1991; van Ooij et al., 1992)) as well as hormone response elements. There are glucocorticoid response elements in the promoter (Duester et al., 1986), and expression of the gene is activiated in hepatoma cells exposed to dexamethasone (Wolfla et al., 1988; Dong et al., 1988; Winters et al., 1990). Retinoic acid response elements are present in the mouse and human ADH3 gene (Duester et al., 1991), and transfection studies demonstrate retinoic acid responsiveness of the promoter. Androgens induced mouse kidney ADH many fold by an effect that is mainly transcriptional (Ceci et al., 1986; Felder et al., 1988). Other hormone responses are less well understood. Estradiol is reported to induce ADH activity in the kidney (Qulali et al., 1991; Dembic and Sabolic, 1982), but not liver, of rats, and thyroid hormone reduces liver ADH activity (Potter and Mezey, 1983; Mezey and Potter, 1981).