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Biomedical subjects

G J Dutton

Publications and source records attributed to G J Dutton.

21 records · Page 2Linked to original sources

Precocious development of glucuronidating and hydroxylating enzymes in chick embryos treated with pituitary grafts.

1. Initiation of precocious development of UDP-glucuronyltransferase by an endogenous factor is reported for the first time. 2. This development occurs in chick embryo liver and kidney after grafting of the cephalic lobe of chicken pars-distalis pituitary tissue on to the chorioallantoic membrane, and in liver results in a rise in the enzyme activity from virtually zero to ;adult' values. Aniline hydroxylase also precociously develops in the liver of grafted embryos, its activity rising from one-third to the full adult value. Specific activities of glucose 6-phosphatase, cytochrome P-450 and NADPH-cytochrome c reductase did not significantly change. 3. The response of the transferase does not require the presence of host pituitary gland nor, apart from 1 day's necessary initiation, the presence of the graft itself. 4. The host becomes competent to respond on the 14th day of incubation; response continues for at least 3 days after removal of the graft, and for 2 days in the isolated liver. Grafting of embryonic pars distalis younger than 17 days does not evoke a response in the host liver. 5. Secretion of the pituitary factor increases suddenly some 24-48h before the naturally developing surge in liver UDP-glucuronyltransferase activity and may be responsible for initiating this rise in vivo. 6. The factor is probably not a growth or luteinizing hormone; its nature and the likelihood of a secondary hormone acting directly on the liver are discussed.

Adrenal Glands

Delayed induction by phenobarbital of udp-glucuronyltransferase activity towards bilirubin in fetal liver.

Phenobarbital pretreatment of pregnant mice (ASH/TO strain) gave rise to approximately equal concentrations of phenobarbital in both maternal and fetal liver. This pretreatment resulted in increased UDP-glucuronyltransferase (GT) activity towards bilirubin in maternal and neonatal liver in fetal liver on days 19 and 20 but in livers from earlier (15-18 day) fetuses GT either was not significantly increased or remained undetectable. Fetal liver is thus not competent to respond to phenobarbital by increasing its GT activity, until just before birth. This pattern persisted through changes in assay conditions and is contrasted with that occuring in embryos free from maternal influence. GT from adult and neontal liver is activated by 0.2 per cent digitonin; in fetal liver this response also does not appear until day 19.

Animals

Relationship beteen activation of "detoxicating" enzymes in stored broken-cell preparations and in autolysing liver.

Activity of UDP-glucuronyltransferase (GT) towards o-aminophenol, p-nitrophenol and bilirubin has been followed in portions of mouse liver stored for periods up to 24 h and in mouse-liver homogenates stored under similar conditions of time and temperature. In both preparations and for all three substrates the pattern of change of GT activity was closely similar. Activity decreased initially, then rose to an optimum higher than in fresh tissue before finally falling. Overall glucuronidation, as measured in slices, also follwed this pattern. The effect of cycloheximide and of detergents, and the levels of UDP-glucose dehydrogenase, UDP-glucuronic acid and aniline hydroxylase were also studied. It is concluded that autolysing liver tissue passes through a period of increased GT activity and glucuronidation corresponding in onset with spontaneous activation of GT in stored homogenates and probably originating by a similiar mechanism. This increase contrasts with progressive fall in hydroxylating activity. The latency of GT in vivo and the value of its activation in damaged liver are discussed.

Aniline Hydroxylase