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J. Biochem, 2003, Vol. 134, No. 5 641-653
© 2003 Japanese Biochemical Society

BIOCHEMISTRY

In Vivo Modification of the UDP-Glucuronosyltransferase Functional State in Rat Liver Following Hypophysectomy and Partial or Complete Hormonal Restoration

Françoise Guéraud*,1, Denis Daveloose2, Hervé Vezin2, Jacques Viret2 and Alain Paris1

1 Laboratoire des Xénobiotiques, Institut National de la Recherche Agronomique (INRA), 180 chemin de Tournefeuille, B.P. 3, 31931 Toulouse Cédex 9, France; and 2 Unité de Biophysique, Centre de Recherches du Service de Santé des Armées (CRSSA), B.P. 87, 38702 La Tronche Cédex, France

The effects of growth hormone on the uridine diphosphate glucuronosyltransferase functional state, biophysical membrane parameters (order parameters and rotational correlation frequency) and the composition in phospholipids were studied in male rat hepatic microsomes. Sham-operated and hypophysectomized animals were injected with two different dosages of growth hormone, mimicking either the male or female growth hormone secretion pattern. Half the animals received thyroxine and cortisol in concentrations chosen to compensate for the lack of thyroid hormones and glucocorticoids in hypophysectomized rats. Growth hormone treatment resulted in a decrease in the latency (that gives a quantification of uridine diphosphate glucuronosyltransferase functional state) of the glucuronidation activities towards various substrates (testosterone, androsterone, bilirubin and 4-nitrophenol). This decrease with growth hormone treatment was particularly evident in hypophysectomized animals that had received cortisol and thyroxine supplementation treatment. These modifications were strongly correlated with modifications in the microsomal membrane lysophospholipid content and to a lower extent with microsomal membrane fatty acid composition. The cytosolic phospholipase A2-dependent increase in the lysophospholipid content in the endoplasmic reticulum is probably a major determinant in the regulation of the functional state of glucuronoyltransferases in response to high dosage growth hormone treatment.

* To whom correspondence should be addressed. Tel: +33-561-285-383, Fax: +33-561-285-244, E-mail: fgueraud{at}toulouse.inra.fr


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