Growth hormone depresses ethylmorphine demethylase activity: correlation with decreased levels of fast-turnover cytochrome P-450 in hypophysectomized female rats

1988 ◽  
Vol 66 (7) ◽  
pp. 868-872
Author(s):  
Birgit M. Vockentanz ◽  
Bruce B. Virgo
Keyword(s):  
Growth Hormone ◽  
Cytochrome C ◽  
Female Rats ◽  
Monooxygenase System ◽  
Demethylase Activity ◽  
Hepatic Monooxygenase ◽  
Cytochrome P 450 ◽  
Slow Turnover ◽  
Nadph Cytochrome C Reductase

The hepatic monooxygenase system was studied in hypophysectomized female rats infused for 5 days with ovine growth hormone (GH). At 7.5 μg∙h−1 GH decreased the total cytochrome P-450 by 16%; at 10 μg∙h−1 it reduced both cytochrome P-450 (31%) and the activity of ethylmorphine demethylase (31%). GH did not alter the activities of NADPH cytochrome c reductase or aniline hydroxylase. The lower GH dose decreased the amount of fast- and slow-turnover P-450 by 11 and 38%, respectively, while the higher dose decreased both by 49%. The loss of demethylase activity therefore correlates with the loss of fast-tumover P-450. This component is relatively more abundant in the female (fast: slow turnover of 4.3) than the male (fast: slow turnover of 2.5). GH did not affect the half-lives of the P-450 components, suggesting that it decreases their synthesis. The P-450 concentration in microsomes from GH-treated animals did not increase after incubation with hemin, suggesting that in vivo the hormone does not lower P-450 synthesis via depression of heme. Puromycin mimicked the effect of GH and when given with the hormone their effects on the P-450 levels were multiplicative (p < 0.05), suggesting different modes of action and that GH does not decrease P-450 by acting at translation.

Release of ferrous iron from ferritin by liver microsomes: a possible role in the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin

1984 ◽  
Vol 62 (12) ◽  
pp. 1293-1300 ◽  
Author(s):  
Bruce Rowley ◽  
George D. Sweeney
Keyword(s):  
Cytochrome C ◽  
Flavin Mononucleotide ◽  
Monooxygenase System ◽  
Iron Release ◽  
Cytochrome C Reductase ◽  
Nadph Cytochrome ◽  
Ferritin Iron ◽  
Tetrachlorodibenzo P Dioxin ◽  
Cytochrome P 450 ◽  
Nadph Cytochrome C Reductase

Nonheme iron is synergistic with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in producing hepatotoxicity in mice. Fe2+ rather than Fe3+ is the probable toxin and we speculated that TCDD, an inducer of microsomal electron transport, might favour reduction of iron. We have defined a system which will release Fe2+ from ferritin (Fe3+) under anaerobic conditions and in the presence of added flavin mononucleotide (FMN). The rate of reduction of ferritin iron was proportional (a) to microsomal protein from 0.5 to >3 mg/mL, (b) to the activity of NADPH–cytochrome c reductase over 0.1 U/mL, (c) to ferritin at concentrations exceeding iron concentrations >200 μmol/L, and (d) to the concentration of FMN when it was less than 125 μmol/L. The system was approximately twice as active with NADPH as with NADH as electron donor. The linear phase of iron release did not commence immediately, but followed a delay (±0.5 min) after adding FMN to an anaerobic mixture containing microsomes, ferritin, an NADPH-generating system, and an oxygen-scavenging system. When microsomes from untreated, Phenobarbitaltreated (3 days), or TCDD-treated (1 or 3 weeks) rats were compared, iron release correlated most closely with the cytochrome P-450 concentration. However, when the microsomal proteins were solubilized and the NADPH–cytochrome c reductase and cytochrome P-450 activities were separated, reduction of ferritin iron was shown to be a function only of the reductase fraction, except that the delay in initiating release of Fe2+ was increased with purified reductase and decreased when a monooxygenase system was reconstituted with cytochrome (phenobarbital or TCDD induced) and lipid. These studies have defined a potentially important hepatic microsomal system able to release Fe2+ from ferritin iron, but have failed to indicate any feature unique to the dioxin-induced monooxygenase system.

scholarly journals Changes in drug-metabolizing activities in the livers of suckling rats as a result of treatment of the lactating mothers with phenobarbitone and chlorpromazine

1971 ◽  
Vol 122 (1) ◽  
pp. 41-47 ◽  
Author(s):  
F. J. Darby
Keyword(s):  
Cytochrome C ◽  
Drug Metabolism ◽  
Female Rats ◽  
Suckling Rats ◽  
Cytochrome C Reductase ◽  
Nadph Cytochrome ◽  
Lactating Mothers ◽  
Cytochrome P 450 ◽  
Nadph Cytochrome C Reductase

1. Lactating female rats were treated with phenobarbitone or chlorpromazine. 2. Hepatic microsomal fractions from the suckling offspring were studied to see if changes had occurred in the rates of drug metabolism. 3. Treatment with phenobarbitone significantly increased the cytochrome P-450 concentration, the activity of NADPH–cytochrome c reductase (EC 1.6.2.3) and the rates of metabolism of aniline, ethylmorphine and [2-14C]pentobarbitone. 4. Treatment with chlorpromazine produced only small increases in the cytochrome P-450 concentration and the rate of hydroxylation of aniline.

Temperature Influence on Basal Activity and Induction of Mixed Function Oxygenase Activity in Fundulus heteroclitus

1979 ◽  
Vol 36 (11) ◽  
pp. 1400-1405 ◽  
Author(s):  
John J. Stegeman
Keyword(s):  
Cytochrome C ◽  
Fundulus Heteroclitus ◽  
Reductase Activity ◽  
Control Fish ◽  
Cytochrome C Reductase ◽  
Nadph Cytochrome ◽  
Pyrene Hydroxylase ◽  
Mixed Function Oxygenase ◽  
Cytochrome P 450 ◽  
Nadph Cytochrome C Reductase

Treatment of Fundulus heteroclitus acclimated to 6.5 °C with benzo(a)pyrene did not elicit any change in the levels of hepatic microsomal NADH- or NADPH-cytochrome c reductase activity, nor in the levels of cytochrome P-450 or its catalytic activities. However, the same treatment offish at 16 5 °C resulted in a marked induction of benzo(a)pyrene hydroxylase and NADPH-cytochrome c reductase. Cytochrome P-450 content was also higher in the warm, treated fish and the Soret maximum of reduced, CO-treated microsomes was shifted to the violet. Levels of aminopyrine demethylase and NADH-cytochrome c reductase activities did not show a significant treatment effect. At neither temperature could treated and control fish be distinguished on the basis of in vitro inhibition of benzo(a)pyrene hydroxylase activity by 7,8-benzoflavone. Levels of NADPH-cytochrome c reductase and benzo(a)pyrene hydroxylase activities were greater in control Fundulus acclimated to 6.5 °C than to 16.5 °C, when normalized to microsomal protein, but not when based on body weight. The results indicate that habitat temperature alone may not affect the capacity for initial hydrocarbon metabolism in fish, but that it can strongly influence the induction of cytochrome P-450. Key words: temperature, cytochrome P-450, hydrocarbon metabolism, mixed-function oxygenase, Fundulus heteroclitus

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

1975 ◽  
Vol 152 (2) ◽  
pp. 325-331 ◽  
Author(s):  
Graham J. Wishart ◽  
Geoffrey J. Dutton
Keyword(s):  
Chorioallantoic Membrane ◽  
Pars Distalis ◽  
Liver And Kidney ◽  
Embryo Liver ◽  
First Time ◽  
Cytochrome P 450 ◽  
Isolated Liver ◽  
Precocious Development ◽  
Nadph Cytochrome C Reductase

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.

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