Sexual dimorphic expression of ADH in rat liver: importance of the hypothalamic-pituitary-liver axis

Abstract

Hepatic alcohol dehydrogenase (ADH) activity is higher in female than in male rats. Although sex steroids, thyroid, and growth hormone (GH) have been shown to regulate hepatic ADH, the mechanism(s) for sexual dimorphic expression is unclear. We tested the possibility that the GH secretory pattern determined differential expression of ADH. Gonadectomized and hypophysectomized male and female rats were examined. Hepatic ADH activity was 2.1-fold greater in females. Because protein and mRNA content were also 1.7- and 2.4-fold greater, results indicated that activity differences were due to pretranslational mechanisms. Estradiol increased ADH selectively in males, and testosterone selectively decreased activity and mRNA levels in females. Effect of sex steroids on ADH was lost after hypophysectomy; infusion of GH in males increased ADH to basal female levels, supporting a role of the pituitary-liver axis. However, GH and L-thyroxine (T4) replacements alone in hypophysectomized rats did not restore dimorphic differences for either ADH activity or mRNA levels. On the other hand, T4 in combination with intermittent administration of GH reduced ADH activity and mRNA to basal male values, whereas T4 plus GH infusion replicated female levels. These results indicate that the intermittent male pattern of GH secretion combined with T4 is the principal determinant of low ADH activity in male liver.

The effects of pregnancy on ethanol clearance

“…Many reports suggest that hormones can affect in vivo and in vitro expression and/or activities of the two major alcohol metabolizing hormones, alcohol dehydrogenase (ADH) and CYP2E1 (Mezey et al, 1994;Potter et al, 1993;Simon et al, 2002;Mezey et al, 1981). Thus, it should probably not be surprising that ethanol clearance differs during pregnancy.…”

Post-transcriptional Regulation of Sterol Regulatory Element-binding Protein-1 by Ethanol Induces Class I Alcohol Dehydrogenase in Rat Liver

“…Expression of SREBP-1 in Hypophysectomized Rats-ADH mRNA and ADH-specific activity were previously reported to be 2-fold greater in male hypophysectomized rats than in intact sham-operated rats (32). We examined the ADH protein in whole cell lysates and the SREBP-1 protein in nuclear extracts from hypophysectomized rats to determine whether there was an inverse relationship between ADH and SREBP-1.…”

Evaluation of the rodent Hershberger bioassay: Testing of coded chemicals and supplementary molecular-biological and biochemical investigations

“…Surprisingly, treatment with 0.4 mg/kg s.c. TP was unable to restore the affected enzyme activities. Both Janeczko et al (1990) and Simon et al (2002) reported restoration of CYP 2C11 expression in young adult castrated rats by androgens following treatment with either 50 g/kg s.c. methyltrienolone for 1 week or with 2 g/kg s.c. testosterone enanthate for 2 weeks. It cannot be excluded that the high dose of TP administered in our study interfered with the pulsatile male-specific growth hormone secretion pattern, the prerequisite for optimal CYP 2C11 expression.…”