Harding et al. (1988) used a rat kidney phenol UDP-glucuronosyltransferase (UDPGT; EC 2.4.1.17 ) cDNA to isolate a
human phenol UDP-glucuronosyltransferase cDNA from a human liver cDNA library. Transfection of a recombinant
plasmid containing the clone into COS-7 cells allowed the expression of a protein of about 55 kD. The expressed
enzyme rapidly catalyzed the glucuronidation of 1-naphthol, 4-methylumbelliferone, and 4-nitrophenol but did not catalyze the glucuronidation of testosterone, androsterone, and estrone.
NCBI Summary:
This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The preferred substrate of this enzyme is bilirubin, although it also has moderate activity with simple phenols, flavones, and C18 steroids. Mutations in this gene result in Crigler-Najjar syndromes types I and II and in Gilbert syndrome. [provided by RefSeq, Jul 2008]
General function
Metabolism, Enzyme, Transferase
Comment
Cellular localization
Cytoplasmic
Comment
Loss of WT1 expression in the endometrium of infertile PCOS patients: a hyperandrogenic effect? Gonzalez D et al. (2012) In fertile patients the endometrial Wilms tumor suppressor gene (WT1) is expressed during the window of implantation. Polycystic ovary syndrome (PCOS) patients suffer from hyperandrogenemia and infertility and have elevated endometrial androgen receptor (AR) expression. WT1 is known to be down-regulated by AR. Therefore, the expression of WT1 and its targets may be altered in PCOS endometrium. The objective of the study was to assess the expression and regulation of WT1 and selected downstream targets in secretory endometrium from ovulatory PCOS (ovPCOS) and fertile women. Endometrial samples were obtained from 25 ovPCOS and 25 fertile patients. Endometrial expression of WT1 and selected downstream targets were assessed by immunohistochemistry and RT-PCR. The androgen effect on WT1 expression was determined in vitro by immunoblots and RT-PCR. The expression of WT1 and its targets was quantified in fertile and ovPCOS stromal cells in the presence of androgens by RT-PCR. Caspase-3/7 activity was measured to evaluate sensitivity to drug-induced apoptosis. WT1 expression was down-regulated in secretory-phase ovPCOS endometrium. Stromal expression of Bcl-2 and p27 was higher, and epidermal growth factor receptor was lower in ovPCOS than in fertile patients. Endometrial stromal expression of WT1, Bcl-2, Bcl-2-associated X protein, and β-catenin was regulated by androgens. Apoptosis levels were reduced in ovPCOS samples and androgen-treated fertile samples. WT1 expression is down-regulated in ovPCOS endometrium during the window of implantation. Androgens regulate the expression of WT1 and its targets during endometrial decidualization. The altered balance between WT1 and AR in the endometrium of PCOS patients may jeopardize the success of decidualization and endometrial receptivity.//////////////////
Ovarian function
Comment
Bostrom M, et al reported the conjugation of 1-naphthol in primary cell cultures of rat
ovarian cells.
Two phase II enzymes catalyzing conjugation, i.e. phenol sulfotransferase (P-SULT) and phenol UDP-glucuronosyltransferase (P-UGT), were
measured using I-naphthol as substrate. After 20 h of incubation the rate of conjugation in cells isolated from ovaries enriched in corpora lutea (CL)
exceeded the rate in cells isolated from ovaries enriched in preovulatory follicles. In addition, when the granulosa cells were removed from the preovulatory follicles, the rate of conjugation was 1.7-fold higher, i.e. in
the theca/stroma cells. When the cells were incubated with 1-[C-14]naphthol
and conjugates were subsequently separated by thin-layer chromatography,
naphthyl glucuronide was the only conjugate observed. Pentachlorophenol (PCP),
a commonly used inhibitor of P-SULT, inhibited 1-naphthol conjugation 50% in
cell cultures, as well as in microsomal preparations, alpha-Naphthoflavone
(ANF) and ellipticine (ELP), both cytochrome P450 (CYP) inhibitors, affected
the conjugation of 1-naphthol in different ways; ANF did not affect P-UGT
activity in microsomal preparations, but inhibited 1-naphthol conjugation in
cell cultures by as much as 90%. On the other hand, ELF inhibited the
conjugation of 1-naphthol up to 99% in the cell cultures, but only 75% in
microsomal fractions. Testosterone (TST) and estradiol inhibited this activity
approximate to 50% in both of these experimental systems. The present findings demonstrate that
P-UGT is by far the major enzyme conjugating 1-naphthol in the rat ovary and that commonly used inhibitors of P-SULT and CYPs also inhibit P-UGT activity,
either directly or via other mechanisms.
Expression regulated by
Comment
Ovarian localization
Luteal cells
Comment
Bostrom M, et al 2004 reported detailed analytical subcellular fractionation of non-pregnant porcine corpus luteum reveals peroxisomes of normal size and significant UDP-glucuronosyltransferase activity in the high-speed supernatant.
A detailed subfractionation of the non-pregnant porcine corpus luteum (CL) was performed employing differential centrifugation. Marker enzyme assays (i.e., lactate dehydrogenase for the cytosol, NADPH-cytochrome P450 reductase for the endoplasmatic reticulum, catalase (CAT) for peroxisomes, glutamate dehydrogenase for the mitochondrial matrix and acid phosphatase for lysosomes) in all subfractions obtained exhibited a pattern of distribution similar to that observed with rat liver. These subfractions should be useful in connection with many types of future studies.In disagreement with previous biochemical and morphological studies, peroxisomes (identified on the basis of catalase activity and by Western blotting of catalase and of the major peroxisomal membrane protein (PMP-70)) sedimented together with mitochondria (i.e., at 5000xg(av) for 10min) and not in the post-mitochodrial fraction prepared at 30,000xg(av) for 20min by Peterson and Stevensson [Biochim. Biophys. Acta 1135 (1992) 207]. No other classical peroxisomal enzymes were detectable in the porcine ovary, raising questions concerning the function of peroxisomes in this organ.Furthermore, UDP-glucuronosyltransferase (UGT), generally considered to be an integral membrane protein anchored in the endoplasmatic reticulum, was recovered in both the cytosolic (i.e., the supernatant after centrifugation at 50,000xg(av) for 1h) and the microsomal fraction of the porcine corpus luteum, even upon further centrifugation of the former. In contrast, UGT sediments exclusively in the microsomal fraction upon subfractionation of the liver and ovary from rat.