Sex differences in the excretion of glucuronide conjugates: the role of intrarenal glucuronidation.

Female Fischer 344 rats administered p-nitrophenol (0.05 mmol/kg) excrete more p-nitrophenylglucuronide in the urine than males (35.9 +/- 2.9 vs. 14.1 +/- 4.0% of total urinary metabolites, respectively). In contrast, hepatic microsomes prepared from male rats have higher UDP-glucuronyltransferase activity toward p-nitrophenol than hepatic microsomes from females (6.49 +/- 0.67 vs. 3.20 +/- 0.17 nmol/min/mg of protein, respectively). Sex differences in p-nitrophenylglucuronide excretion may be due to sex differences in either biliary excretion of glucuronide conjugate or in extrahepatic conjugation of p-nitrophenol. UDP-glucuronyl-transferase activity in renal microsomes prepared from male and female rats toward p-nitrophenol was 0.21 +/- 0.09 nmol/min/mg of protein and 0.91 +/- 0.02 nmol/min/mg of protein, respectively. Vmax was greater in females than in males; Km was not sex linked. Similar in vitro sex differences were also observed with 1-naphthol as the aglycone. In contrast, renal microsomes prepared from male or female rats did not glucuronidate morphine. Likewise, no sex differences in the excretion of morphine glucuronide were observed (16.4 +/- 4.8 vs. 23.9 +/- 5.3% of total urinary conjugates from males and females, respectively). Renal conjugation of p-nitrophenol in vivo was determined using the "Specific Activity Difference Ratio" technique. During infusion of 2 mumol/min/kg of p-nitrophenol, 897.9 +/- 26.0 nmol/min/kg of in vivo formed p-nitrophenylglucuronide was excreted in the urine of female rats whereas 715.6 +/- 65.9 nmol/min/kg was excreted in males.(ABSTRACT TRUNCATED AT 250 WORDS)