Abstract
The aim of our study was to localise UDP-glucuronosyltransferase (UDPGT) in the developing mesonephric and metanephric kidneys of the human embryo and fetus, using immunohistochemical methods and an antibody preparation with broad specificity to the human isoforms. In embryonic and early fetal development of the metanephric kidney, UDPGT is located primarily in derivatives of the ureteric bud such as the ureter, pelvis, calyces and collecting ducts. This early predominance of UDPGT to ureteric bud derivatives declines by mid-fetal life: a) as nephrons evolve and develop they become increasingly UDPGT immunoreactive such that in mature metanephric kidney, the proximal tubules are highly UDPGT reactive, with other elements of the nephron also immunopositive (albeit at lower reactivities) and b) with the formation of an immunonegative transitional epithelium in ureter, pelvis and calyces, the reactivity retained in collecting ducts is only a small proportion of the total. The distribution of UDPGT immunoreactivity is relatively uniform in proximal tubular cells throughout development. This is in contrast to collecting ducts where, in fetal life, this reactivity is displaced to apices and bases by intracellular glycogen deposits. Parietal cells of Bowman’s capsule are immunoreactive, but glomeruli are negative. In mesonephric kidney, as early as 32 days post-ovulation, tubules and the mesonephric duct are UDPGT immunoreactive and mesonephric immunopositivity overlaps with that in the developing metanephric kidney.
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References
Burchell B (1974) UDP-Glucuronyltransferase activity towards oestriol in fresh and cultured foetal tissues from man and other species. J Steroid Biochem 5: 261–267
Burchell B, Coughtrie MWH (1989) UDP-Glucuronosyltransferases. Pharmacol Ther 43: 261–289
Burchell B, Kennedy S, Jackson M, McCarthy L (1984) The biosynthesis and induction of microsomal UDPGT in avian liver. Biochem Soc Transact 12: 50–53
Burchell A, Gibb L, Waddell ID, Giles M, Hume R (1990) The ontogeny of the human hepatic microsomal glucose-6-phosphatase proteins. Clin Chem 36: 1633–1637
Coughtrie MWH, Burchell B, Shepherd IM, Bend JR (1987) Defective induction of phenol glucuronidation by 3-methylcholanthrene in Gunn rats is due to the absence of a specific UDP-glucurosyltransferase isozyme. Mol Pharmacol 31: 585–591
Coughtrie MWH, Burchell B, Leakey JEA, Hume R (1988) The inadequacy of perinatal glucuronidation: immunoblot analysis of the developmental expression of individual UDP-glucuronosyltransferase isozymes in rat and human liver microsomes. Mol Pharmacol 34: 729–735
Coughtrie MWH, Ask B, Rane A, Burchell B, Hume R (1989) The enantioselective glucuronidation of morphine in rats and humans. Biochem Pharmacol 38: 3273–3280
Dahl-Puustinen M-L, Dumont E, Bertilsson L (1989) Glucuronidation of E-10-hydroxynorthyrptiline in human liver, kidney, and intestine. Drug Metab Dispos 17: 433–436
Dutton GJ (1966) The biosynthesis of glucuronides. In: Dutton GJ (ed) Glucuronic acid. Academic Press, New York, pp 186–188
Dutton GJ (1980) Extrahepatic glucuronidation. In: Dutton GJ (ed) Glucuronidation of drugs and other compounds. CRC Press, Boca Raton, Florida, pp 149–158
Dutton GJ, Ko V (1966) The synthesis of o-aminophenol glucuronide in several tissues of the domestic fowl, Gallus gallus, during development. Biochem J 99: 550–556
Gawronska-Szklarz B, Svensson J-O, Widen J, Rane A (1985) Differential hepatic glucuronidation of (−)- and (+)-morphine in the rat and human fetus. In: Matern S, Bock KW, Gerok W (eds) Advances in glucuronide conjugation. MTP Press, Lancaster, pp 335–340
Hiley C, Bell J, Hume R, Strange R (1989) Differential expression of alpha and pi isoenzymes of glutathione S-transferase in developing human kidney. Biochim Biophys Acta 990: 321–324
Hjelle JJ (1986) Hepatic UDP-glucuronic acid regulations during acetaminophen biotransformation in rats. J Pharmacol Exp Ther 228: 407–413
Hobkirk R, Green RN, Nilsen M, Jennings BA (1974) Formation of estrogen glucosiduronates by human kidney homogenates. Can J Biochem 52: 9–14
Hume R, Bell J, Gourlay M, Giles M, Hallas A, Cossar D, Kelly R (1993). Prostaglandin production and metabolism in self-differentiating human fetal lung organ culture. Exp Lung Res 19: 361–376
Jones CT (1982) Biochemical development of the fetus and neonate. In: Jones CT (ed) Biochemical development of the fetus and neonate. Elsevier, Amsterdam, pp 249–286
Kawade N, Onishi S (1981) The prenatal and postnatal development of uridine diphosphate glucuronosyltransferase activity towards bilirubin and 2-aminophenol in human liver. Biochem J 196: 257–260
Leakey JEA, Hume R, Burchell B (1987) Development of multiple activities of UDP-glucuronosyltransferase in human liver. Biochem J 243: 859–861
Lipschitz WL, Bueding E (1939). Mechanisms of the biological formation of conjugated glucuronic acid. J Biol Chem 129: 333–358
Matern S, Matern H, Farthmann EH, Gerok W (1984) Hepatic and extrahepatic glucuronidation of bile acids in man. J Clin Invest 74: 402–410
Mellor JD, Hobkirk R (1975) In vitro synthesis of estrogen glucuronides and sulfates by human renal tissue. Can J Biochem 53: 779–783
Onishi S, Kawade N, Itoh S, Isobe K, Sugiyama S (1979) Post-natal development of uridine diphosphate glucuronosyltransferase activity towards bilirubin and 2-aminophenol in human liver. Biochem J 184: 705–707
O’Rahilly, R, Muller F (1987) Developmental stages in human embryos. Publications 637. Caregie Institution of Washington, Washington
Parquet M, Pessah M, Sacquet E, Salvat C, Reizman A (1988) Effective glucuronidation of 6-alpha-hydroxylated bile acids by human hepatic and renal microsomes. Eur J Biochem 171: 329–334
Peters WHM, Jansen PLM (1988) Immunocharacterisation of UDP-glucuronyltransferase isoenzymes in human liver, intestine and kidney. Biochem Pharmacol 37: 564–567
Peters WHM, Allebes WA, Jansen PLM, Poels LG, Capel PJA (1987) Characterisation and tissue specificity of a monoclonal antibody against human uridine 5′-diphosphate-glucuronosyltransferase. Gastroenterology 93: 162–169
Potter EL (1972) Normal and abnormal development in the kidney. Year Book, Chicago
Roy Chowdhury J, Novikoff PM, Roy Chowdhury N, Novikoff AB (1985) Distribution of UDP glucuronosyltransferase in rat tissue. Proc Natl Acad Sci 82: 2990–2994
Scammon RE, Calkins LA (1929) The development and growth of the external dimensions of the human body in the fetal period. University of Minesota Press, Minneapolis
Sternberger LA, Hardy PH, Cuculis J, Meyer HG (1990) The unlabelled antibody method of immunohistochemistry: preparation and properties of soluble antigen — antibody complex (Horseradish peroxidase-anti-horseradish peroxidase) and its use in identification of spirochaetes. J Histochem Cytochem 18: 315–333
Stevenson IH, Dutton GJ (1962) Glucuronide synthesis in kidney and gastrointestinal tract. Biochem J 82: 330–334
Yue Q, Odar-Cedarlof I, Svensson J-O, Sawe J (1988) Glucuronidation of morphine in human kidney microsomes. Pharmacol Toxicol 63: 337–340
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Hume, R., Coughtrie, M.W.H. & Burchell, B. Differential localisation of UDP-glucuronosyltransferase in kidney during human embryonic and fetal development. Arch Toxicol 69, 242–247 (1995). https://doi.org/10.1007/s002040050165
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DOI: https://doi.org/10.1007/s002040050165