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Depression of Glucuronyltransferase Activity by Glucocorticoids in Adult Female Mice¹

Indiana University-Purdue University at Fort Wayne, Fort Wayne, IN 46805

Abstract

Three experiments were conducted to examine the effect of glucocorticoids on glucuronidation in the adult female mouse. In the first experiment, four mice served as controls, while four other mice were each given 80 µg triamcinolone acetonide (TA) at 39, 25, 15 and 1 h before they were killed. Liver homogenates from all animals were assayed for activity of uridine diphospho-glucuronyltransferase (UDP-GT). The mean enzymatic activity was 115 and 58 nmol of -nitrophenol conjugated to glucuronic acid •h^–1 •;mg of hepatic protein^–1 for control and TA-treated mice, respectively (P<.01). In Exp. 2, 48 mice were divided randomly into 12 groups, with four groups of controls, and four each treated with either 100 µg TA or 100 µg dexamethasone (DEX) at –4 and 0 h. All of the mice were given 2.5 mmol phenolphthalein (P) at 0 h. The excretion of free P was similar for all groups: however, mice treated with TA or DEX excreted significantly less P-glucuronide and mice treated with TA excreted significantly less P-sulfate than did the controls. In the third experiment, 30 mice each served as controls or were treated with 80 µg TA or 500 µg metyrapone (M) at –4 and 0 h. Also at 0 h, animals were given .12, .15, .19, .24 or .29 mg -cresol/g of body weight. The LD₅₀ of -cresol for the control, TA- and M-treated groups were .19, .15 and .24 mg of -cresol/g of body weight. The LD₅₀ for the TA-treated group was less than the LD₅₀ of the M-treated group (P<.05), but neither were significantly different from controls. These results suggest that pretreatment of adult female mice with synthetic glucocorticoids reduces the rate of glucuronidation via a depression in the enzymatic activity of UDP-glucuronyltransferase.

¹ This investigation was supported in part by a grant from the Indiana University-Purdue Univ. at Fort Wayne Research and Instructional Development Support Program.

² Dept. of Biol. Sci.

³ Present address: Dept. of Anim. Sci., North Carolina State Univ., Raleigh 27650.