Growth Hormone and Drug Metabolism. Acute Effects on Microsomal Mixed-function Oxidase Activities in Rat Liver

Overview

Journal Biochem J

Specialty Biochemistry

Date 1976 Feb 15

PMID 938458

Citations 5

Authors

J T Wilson

T C Spelsberg

Affiliations

Soon will be listed here.

Abstract

Adult male rats were subjected either to sham operation or to hypophysectomy and adrenalectomy and maintained for a total of 10 days before treatment with growth hormone. Results of the early effects of growth hormone on the activities of the mixed-function oxidases in rat liver over a 96h period after growth-hormone treatment are presented. 2. Hypophysectomy and adrenalectomy result in decreased body and liver weight and decreased drug metabolism (mixed-function oxidases). Concentrations of electron-transport-system components are also decreased. 3. In the hypophysectomized/adrenalectomized rats, growth hormone decreases the activities of the liver mixed-function oxidases and the cytochrome P-450 and cytochrome c reductases, as well as decreasing the concentration of cytochrome P-450 compared with that of control rats. Similar but less dramatic results are obtained with sham-operated rats. 4. It is concluded that whereas growth hormone enhances liver growth, including induction of many enzyme activities, it results in a decrease in mixed-function oxidase activity. Apparently, mixed-function oxidase activity decreases in liver when growth (mitogenesis) increases.

Citing Articles

Vitamin D in pituitary driven osteopathies.

Chiloiro S, Costanza F, Riccardi E, Giampietro A, De Marinis L, Bianchi A Pituitary. 2024; 27(6):847-859.

PMID: 39180644 PMC: 11632065. DOI: 10.1007/s11102-024-01439-3.

Association of Vitamin D Receptor Polymorphisms With Activity of Acromegaly, Vitamin D Status and Risk of Osteoporotic Fractures in Acromegaly Patients.

Jawiarczyk-Przybylowska A, Halupczok-Zyla J, Kolackov K, Gojny L, Zembska A, Bolanowski M Front Endocrinol (Lausanne). 2019; 10:643.

PMID: 31616375 PMC: 6768940. DOI: 10.3389/fendo.2019.00643.

Role of the hypothalamo-pituitary-liver axis in sex differences in susceptibility of the liver to toxic agents.

Gustafsson J, Eneroth P, Hokfelt T, Mode A, Norstedt G, Skett P Environ Health Perspect. 1981; 38:129-41.

PMID: 6263606 PMC: 1568426. DOI: 10.1289/ehp.8138129.

Attempts to phenotype human liver samples in vitro for debrisoquine 4-hydroxylase activity.

Boobis A, Hampden C, Murray S, Beaune P, Davies D Br J Clin Pharmacol. 1985; 19(6):721-9.

PMID: 4027115 PMC: 1463883. DOI: 10.1111/j.1365-2125.1985.tb02706.x.

Growth hormone and drug metabolism. Acute effects on nuclear ribonucleic acid polymerase activity and chromatin.

Spelsberg T, Wilson J Biochem J. 1976; 154(2):439-48.

PMID: 945734 PMC: 1172725. DOI: 10.1042/bj1540439.

References

Burton K . A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956; 62(2):315-23. PMC: 1215910. DOI: 10.1042/bj0620315. View

Omura T, Sato R . THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. I. EVIDENCE FOR ITS HEMOPROTEIN NATURE. J Biol Chem. 1964; 239:2370-8. View

Harris H . TRANSFER OF RADIOACTIVITY FROM NUCLEAR TO CYTOPLASMIC RIBONUCLEIC ACID. Nature. 1964; 202:249-52. DOI: 10.1038/202249a0. View

Bates R, MILKOVIC S, GARRISON M . Concentration of prolactin, growth hormone and ACTH in blood and tumor. of rats with transplantable mammotropic pituitary tumor. Endocrinology. 1962; 71:943-8. DOI: 10.1210/endo-71-6-943. View

Phillips A, Langdon R . Hepatic triphosphopyridine nucleotide-cytochrome c reductase: isolation, characterization, and kinetic studies. J Biol Chem. 1962; 237:2652-60. View

Cooper J, Brodie B . The enzymatic metabolism of hexobarbital (evipal). J Pharmacol Exp Ther. 1955; 114(4):409-17. View

SCHNEIDER W, HOGEBOOM G . Intracellular distribution of enzymes. IX. Certain purine-metabolizing enzymes. J Biol Chem. 1952; 195(1):161-6. View

LOWRY O, ROSEBROUGH N, FARR A, RANDALL R . Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75. View

Wilson J, Frohman L . Concomitant association between high plasma levels of growth hormone and low hepatic mixed-function oxidase activity in the young rat. J Pharmacol Exp Ther. 1974; 189(1):255-70. View

10.

Wilson J . The effect of a pituitary mammotropic tumor on hepatic microsomal drug metabolism in the rat. Biochem Pharmacol. 1968; 17(7):1449-57. DOI: 10.1016/0006-2952(68)90081-6. View

11.

SASAME H, GILLETTE J . Studies on the relationship between the effects of various substances on absorption spectrum of cytochrome P-450 and the reduction of p-nitrobenzoate by mouse liver microsomes. Mol Pharmacol. 1969; 5(2):123-30. View

12.

Gigon P, Gram T, GILLETTE J . Studies on the rate of reduction of hepatic microsomal cytochrome P-450 by reduced nicotinamide adenine dinucleotide phosphate: effect of drug substrates. Mol Pharmacol. 1969; 5(2):109-22. View

13.

Schenkman J, Remmer H, Estabrook R . Spectral studies of drug interaction with hepatic microsomal cytochrome. Mol Pharmacol. 1967; 3(2):113-23. View

14.

Gigon P, Gram T, GILLETTE J . Effect of drug substrates on the reduction of hepatic microsomal cytochrome P-450 by NADPH. Biochem Biophys Res Commun. 1968; 31(4):558-62. DOI: 10.1016/0006-291x(68)90514-7. View

15.

Wilson J . Decreased hepatic microsomal drug metabolism after the injection of a mixture containing somatotropin, corticotropin and prolactin. Biochem Biophys Res Commun. 1968; 32(6):903-7. DOI: 10.1016/0006-291x(68)90112-5. View

16.

Wilson J . Pituitary mammotropic tumor in rats: evidence for a dosage effect on organ weight and liver drug metabolism. J Natl Cancer Inst. 1969; 43(5):1067-72. View

17.

Wilson J . Further observations on hepatic drug metabolism in rats treated with a mixture of somatotropin, corticotropin and prolactin. Life Sci. 1969; 8(19):1095-102. DOI: 10.1016/0024-3205(69)90162-3. View

18.

Wilson J . Identification of somatotropin as the hormone in a mixture of somatotropin, adrenocorticotropic hormone and prolactin which decreased liver drug metabolism in the rat. Biochem Pharmacol. 1969; 18(8):2029-31. DOI: 10.1016/0006-2952(69)90300-1. View

19.

Fouts J . Some in vitro assay conditions that affect detection and quantitation of phenobarbital-induced increases in hepatic microsomal drug-metabolizing enzyme activity. Toxicol Appl Pharmacol. 1970; 16(1):48-65. DOI: 10.1016/0041-008x(70)90161-4. View

20.

Wilson J . Altered rat hepatic drug metabolism after implantation of a pituitary mammotropic tumor (MtT), Walker carcinosarcoma or adenocarcinoma and after removal of the MtT. Endocrinology. 1971; 88(1):185-94. DOI: 10.1210/endo-88-1-185. View