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Title: Regulation of mouse hepatic glutathione S-transferases
Author: Dolan, Catherine
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1991
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The glutathione S-transferases (GST) are a multi-gene family of dimeric proteins which catalyse the conjugation of glutathione to a wide range of electrophilic compounds. Three classes of mouse cytosolic GST have been isolated, alpha, mu and pi, comprising Ya-, Yb- and Yf-type subunits respectively. A marked sexual dimorphism in mouse hepatic GST has been observed. The YfYf GST is the most abundant form in the male, constituting approximately 70% of total hepatic GST content. By contrast, the Yf subunit represents only a minor form in the livers of female mice. The hormonal controls which regulate the expression of the YfYf GST in mouse liver have been investigated. Testosterone, the major male sex hormone, is found to regulate the levels of Yf in mouse liver. Castration of the male leads to a decline in the levels of Yf to that observed in females. Replacement therapy with testosterone partially restores the levels of Yf. Testosterone treatment induces expression of this subunit in the female. Growth hormone secretion from the pituitary gland differs markedly between the sexes. Androgens act to produce the male pattern of growth hormone secretion which regulates the sex-specific expression of numerous hepatic proteins. Male 'little mice', specifically defective in the production of growth hormone, exhibit a feminine pattern of GST expression, despite having normal levels of testosterone. Testosterone treatment has no effect on the expression of YfYf in little mice. In contrast, growth hormone replacement therapy, administered to simulate the male-specific pattern causes an increase in the expression of the Yf subunit. These findings strongly suggest that testosterone regulates the hepatic expression of the Yf subunit indirectly through the male-specific pattern of growth hormone secretion. The effects of the xenobiotics, phenobarbital, dexamethasone and 1,4-Bis[2-(3,5-dichloropyridyloxy)]-benzene (TCBOP) on mouse hepatic GST content have been investigated in two strains of mice, C57BL/6 and DBA/2. All three compounds were found to induce hepatic GST in both strains and sexes, predominately affecting expression of members of the mu class. TCBOP was the most potent inducer. Hypophysectomy did not significantly affect induction of GST by these compounds.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available