Interindividual variability in the glucuronidation and sulphation of ethinyloestradiol in human liver.

Abstract

1 Glucuronidation and sulphation of ethinyloestradiol (EE2) was studied in human liver.Microsomal

Interindividual variability in the N‐sulphation of desipramine in human liver and platelets.

“…N-ST activity is widely distributed in the body, its average activity in extrahepatic tissues being 2-7 fold lower than that in the liver. The rate of hepatic N-sulphation of DMI showed a 3-4 fold greater interindividual variability than those of 2-naphthol (Pacifici et al, 1988) and ethinyloestradiol (Temellini et al, 1991) O-sulphation. The coefficient of variation for platelet N-ST activity was twice that for hepatic N-ST activity.…”

“…The paucity of data on human liver N-and O-sulphotransferases makes it difficult to assess whether these enzymes are under common or different control. The limited evidence available, based on interindividual variability of 2-naphthol (Pacifici et al, 1988) and ethinyloestradiol (Temellini et al, 1991) sulphation, the symmetric frequency distribution histogram of O-sulphotransferase (Temellini et al, 1991) and the higher rate of O-sulphotransferase in ileum than colon (Cappiello et al, 1990b;Pacifici et al, 1989) suggests that O-sulphotransferase and N-ST activity are under independent control. The rates of p-nitrophenol-and dopamine-sulphation measured in 100 human livers do not correlate with the rate of DMI N-ST (unpublished data).…”

“…Anderson et al (1981) found a 15-fold variation of platelet O-sulphotransferase activity. This compared with a 5-7-fold variation in its hepatic activity (Pacifici et al, 1988;Temellini et al, 1991).…”

“…Sulphation of hydroxy groups has been described in human liver and in blood platelets. The hepatic sulphation of 2-naphthol (Pacifici et al, 1988) and ethinyloestradiol (Temellini et al, 1991) varies over a range of 5 and 7-fold, respectively, whereas, in platelets, the sulphation of 3-methoxy-4-hydroxyphenylglycol (Anderson et al, 1981) and minoxidil (Johnson & Baker, 1987) varies over a range of 15-fold. Sulphation at nitrogen atoms has received little attention although alkyl-and aryl-amines are N-sulphated in rat liver (Iwasaki et al, 1983(Iwasaki et al, , 1986Johnson et al, 1982;Ramaswamy & Jakoby, 1987). The (Iwasaki et al, 1986).…”

Polymorphisms for Aromatic Amine Metabolism in Humans: Relevance for Human Carcinogenesis

“…Studies (K. Kaderlik, B. Burchell, and F. F. Kadlubar, unpublished data) using cultured cells that express cloned human UGTlA1 failed to show any activity for the N-hydroxy derivatives of Glu-P-1 or PhIP. With a variety of substrates, a wide variation (4-to 19-fold) in liver UGT activity has been reported (47-49); however, the distribution appears to be unimodal (49). Except in the case of UGT1A2, which is associated with defective bilirubin conjugation diagnostic of the Crigler-Najar syndrome (50), there is as yet no evidence for a polymorphism in human populations.…”