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Biomedical subjects

G J Dutton

Publications and source records attributed to G J Dutton.

At least 19 recordsLinked to original sources
PubMed1979

The formation and distribution of bilirubin monoglucuronide and diglucuronide in rat liver slices.

1. Bilirubin conjugation in rat liver slices was reassessed by using analysis of ethyl anthranilate azopigments to estimate separately the formation of bilirubin mono- and di-glucuronides. 2. Conjugation in slices resembles the situation in vivo more closely than does microsomal conjugation, in that diglucuronide is formed in appreciable quantity. 3. Both bilirubin mono- and di-glucuronides were present in slices in approximately equal amounts, but the monoglucuronide was the major product found in the incubation medium. 4. These results are discussed in relation to recent theories on the relationship between bilirubin mono- and di-glucuronide formation in vivo.

Animals↗
PubMed1979

Differential stimulation of hepatic mono-oxygenase and glucuronidating systems in chick embryo and neonatal rat by glucocorticoids.

White Leghorn embryos infused with corticosterone precociously reproduced the hatching surges of hepatic UDPglucuronosyltransferase activity to 2-aminophenol, aminopyrine N-demethylase activity and cytochrome P-450 concentration. Onset of transferase activity followed that of the others by 48 h over hatching and on infusion. Competence of demethylase and transferase to respond to corticosterone appeared over days 12--14. Glucocorticoids are suggested as the natural triggers of both transferase and monooxygenase activities in chick and both processes may share a further control. Exposure of CD rat foetuses at 18 1/2 days to dexamethasone by maternal injection evoked precocious onset of transferase activity to 2-aminophenol but not to bilirubin, nor of demethylase activity or cytochrome P-450 content. Injection of hour-old or infant rats with dexamethasone did reproduce precociously onset of the three latter and stimulated the former. Competence for glucocorticoid response thus appeared before birth for transferase activity to 2-aminophenol and at birth for the others. Onset of transferase following hatching or glucocorticoid lagged behind that of demethylase or cytochrome P-450 by 48 h in chick embryo and 36 h in newborn and infant rats; only in foetal rat was response of transferase rapid to administered glucocorticoid.

Aminophenols↗
PubMed1977

Regulation of onset of development of UDP-glucuronosyltransferase activity towards o-aminophenol by glucocorticoids in late-foetal rat liver in utero.

1. A precocious development of UDP-glucuronosyltransferase activity (EC 2.4.1.17) towards o-aminophenol is demonstrated in 15-17 day foetal rat liver in utero after dexamethasone administration to the mother. 2. This stimulation of liver transferase activity in utero is directly proportional to the dose of dexamethasone infected. 3. Precocious development of transferase activity in utero can also be effected with the natural glucocorticoid cortisol by multiple injections of large amounts of this hormone into the mother. 4. Transferase activity towards o-aminophenolin foetal lung, kidney and upper alimentary tract can also be precociously stimulated by dexamethasone in 17-day foetuses in utero. 5. Natural development of hepatic transferase activity between days 18 and 20 of gestation is retarded after foetal hypophysectomy by decapitation in utero. 6. Overall glucuronidation of o-aminophenol, as observed in foetal rat liver, is also precociously stimulated by dexamethasone. 7. From this and from evidence previously presented we suggest that glucocorticoids, which are known to increase in rat foetuses between days 17 and 20 of gestation, trigger the normal development in utero of hepatic transferase activity towards o-aminophenol which occurs at that time. We also suggest that these hormones are responsible for the rise in activity of the enzyme in foetal lung, kidney and upper alimentary tract which occurs during the same gestational period.

Aniline Compounds↗
PubMed1977

Precocious development of uridine diphosphate glucuronosyltransferase activity during organ culture of foetal rat liver in the presence of glucocorticoids.

1. Precocious development of mammalian UDP-glucuronosyltransferase (EC 2.4.1.1.7) induced by endogenous compounds of known chemical composition is reported for the first time. 2. This development occurs in cultured explants of foetal rat liver when exposed to corticosteroids possessing a pregn-4'-ene structure and a hydroxy or an oxo group at C-11. 3. Explants from 14-day foetuses cultured for 3 days in a chemically defined medium containing dexamethasone exhibited transferase activities towards o-aminophenol within adult male values. Those liver transferase activities attained in utero by 17 days were still negligible. 4. Evidence from several approaches indicated that the explants required glucocorticoids for expression of the transferase, not for maintenance of viability. 5. Glucocorticoid-dependent stimulation of transferase activity required incorporation of L-[14C]leucine into protein, as judged from the pulsing of cultures with cycloheximide. 6. The relevance of these culture experiments to the situation in vivo is discussed.

Amino Acids↗
PubMed1976

Precocious development of UDP-glucuronyltransferase activity in chick-embryo liver after administration of adrenocorticotropic hormone and of certain 11beta-hydroxy corticosteroids.

1. Precocious development of UDP-glucuronyltransferase (EC 2.4.1.17) and of glucuronidation by endogenous compounds of known chemical composition is reported for the first time. 2. This development occurs precociously in chick-embryo liver after administration to the egg of mammalian adrenocorticotropic hormone, of Synacthen (a synthetic compound possessing adrenocorticotropic activity), or of certain corticosteroids possessing a hydroxy or an oxo group at C-11. 3. Corticosterone-dependent transferase development parallels the rise of infused corticosterone in plasma, but does not require the presence of embryo pituitary in ovo, and is demonstrable in embryo liver explants in vitro. 4. Competence of embryo liver transferase to respond to corticosterone (or dexamethasone) begins over days 13-14, the time of competence to respond to grafted pituitary gland. 5. The transferase appearing after treatment with corticosterone or adrenocorticotropic hormone, like that appearing after pituitary grafting or on natural development and unlike that from the untreated embryo, is markedly activated by membrane-perturbation procedures, suggesting it appears through induction, not activation. 6. Thyroxine and tri-iodothyronine accelerate transferase development after treatment with adrenocorticotropic hormone or corticosteroid to the rate seen after pituitary grafting. 7. A wide range of other hormones and steroids did not obviously influence transferase development in this system. 8. We suggest that grafted pituitary gland evokes precocious transferase development in embryo liver through production of adrenocorticotropic hormone and hence of the active corticosteroids; thyrotropin and thyroxine hasten the process. The role of this mechanism in the natural development of UDP-glucuronyltransferase is discussed.

11-Hydroxycorticosteroids↗
PubMed1975

Induction of UDPglucose dehydrogenase during development, organ culture, and exposure to phenobarbital. Its relation to levels of UDPglucuronic acid and overall glucuronidation in chicken and mouse.

Liver UDPglucose in early chick-enbryo has, by the 19th day of incubation, reached levels existing in young hatched (White Leghorn) chicks. In developing ASH/TO mouse liver, the dehydrogenase is low, but increases sharply at late foetal and weaning stages; adult activity is greater in females than males. The UDPglucuronic acid content of embryo liver from at least 12 days resembles that of adult chicken; in mouse liver it rises over birth and infancy. These differences in relative rates of development of enzyme and nucleotide in the 2 species can explain why overall glucuronidation by liver appears in chick rapidly after hatching, but in mouse only gradually during infancy. UDPglucose dehydrogenase increases in embryo liver, probably by induction, 2-3-fold during culture with phenobarbital and some 5-fold when exposed to the drug in ovo. Phenobarbital treatment also increases the enzyme in late foetal and adult mice, abolishing the sex difference. Differences between induction of UDPglucose dehydrogenase and UDPglucuronyl transferase during development, culture and phenobarbital treatment indicate that control mechanism for these two enzymes are not directly linked.

Alcohol Oxidoreductases↗