Further characterization of hormonal regulation of glutathione transferase in rat liver and adrenal glands. Sex differences and demonstration that growth hormone regulates the hepatic levels

Abstract

Immunoblot experiments and reverse-phase h.p.l.c. were used to study the levels of glutathione transferase subunits 1, 2, 3, 4, 6, 7 and 8 in the liver and adrenal of intact and hypophysectomized male and female Sprague-Dawley rats. A sexual dimorphism in the levels of several of these isoenzymes and in their responses to hypophysectomy was demonstrated. In the liver of sham-operated females and males there are differences in glutathione transferase activities and isoenzyme pattern. H.p.l.c. analysis showed higher levels of subunits 1, 3 and 4 in male rats compared with females. In contrast with the pronounced sex differences in sham-operated rats, the isoenzyme patterns of hypophysectomized males and females were very similar. In the adrenal glands, however, a sexual dimorphism became apparent only after hypophysectomy, when the level of subunit 4 was increased 14-fold in the female, whereas the corresponding increase in the male rat was only 2.7-fold. The hepatic pattern of glutathione transferase subunits could be altered by continuous infusion of growth hormone to both sham-operated and hypophysectomized rats of both sexes. This treatment feminized the isoenzyme pattern in sham-operated males and a similar effect was obtained upon treating hypophysectomized rats with thyroxine, cortisone acetate and a continuous infusion of growth hormone.

Sexual Dimorphism of Rat Liver Nuclear Proteins

“…GH responsiveness is demonstrated here for the first time for phytanoyl-CoA dioxygenase, cysteine sulfinic acid decarboxylase, glutaryl-CoA dehydrogenase, peptidylprolyl isomerase, hnRNP K, hnRNP D-like, hnRNP A3, NF45, betaine homocysteine S-methyltransferase, and CMP-N-acetylneuraminic acid synthetase. Interestingly, GH has been shown to regulate the expression of alcohol sulfotransferase at the level of gene expression (12,48) and the expression of GSTs Yb1 and Yb2 at the gene and protein level (11,44). In the present study, however, these proteins did not display changes in nuclear intensity in response to GH treatment.…”

“…Sexually dimorphic hepatic expression at the mRNA or/and protein level has been demonstrated previously for several of these proteins. These include the male-predominant proteins Nhydroxyarylamine sulfotransferase (12,41), hydroxyacid oxidase 3 (12), cysteine sulfinic acid decarboxylase (42), regucalcin (43), GSTs Yb1 and Yb2 (11,44), and various estrogen sulfotransferases (12,45), and the female-predominant alcohol sulfotransferases (12, 46 -48). The sexually dimorphic pattern of expression of the other proteins identified in this study and listed in Table III is reported here for the first time.…”

Hormonal regulation of glutathione S-transferase expression in co-cultured adult rat hepatocytes

“…In particular, gender differences in GH secretion patterns are involved in the regulation of GSTs in vivo (Staffas et al 1992). Continuous administration of GH yields a female isoenzyme pattern, whereas discontinuous administration of GH yields a male pattern (Staffas et al 1992).…”

“…Several enhancer elements, including the xenobiotic-responsive element (XRE), the antioxidantresponsive element (ARE), the glucocorticoid-responsive element (GRE) and the barbiturate-responsive element (Barbie box) have been identified in the 5 -flanking regulatory region of this gene and are responsible for its induction by polycyclic aromatic hydrocarbons including 3-methylcholanthrene and -naphtoflavone, products of oxidative stress, dexamethasone and phenobarbital respectively (Rushmore et al 1991, Hayes & Pulford 1995. With respect to the endogenous regulation of GST expression, it is known that adrenocorticotrophic (Mankowitz et al 1990), growth (Staffas et al 1992), thyroid (Kelley & Bjeldanes 1995, Beckett et al 1988) and steroid hormones (Hatayama et al 1986) are involved. At the regulatory level, it has been shown that insulin induces the transcription of the human GSTP1 gene via one of the SP-1 sites (GC/box) in the 5 -flanking regulatory region, whilst retinoic acid suppresses hGSTP1 expression through the AP-1 site (Xia et al 1993(Xia et al , 1996.…”

Effects of insulin-like growth factor 1 on glutathione S-transferases and thioredoxin in growth hormone receptor knockout mice

“…The level of GST expression represents an important factor in determining the sensitivity of organisms to endogenous and exogenous compounds and has been shown to decline with aging (Cho et al 2003;Richie et al 1992). Moreover, GH has been shown to regulate the level of cytosolic GSTs in certain target organs (Coecke et al 2000;Srivastava and Waxman 1993;Staffas et al 1992). In our study, although no differences of the M class GSTs in mitochondria were observed, cytosolic GSTM4 was higher in WT mice and increased in IGF-1-treated GHRKO mice.…”