Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1990 Jan 1;265(1):147–154. doi: 10.1042/bj2650147

Increase in the amount of glutathione transferase 4-4 in the rat adrenal gland after hypophysectomy and down-regulation by subsequent treatment with adrenocorticotrophic hormone.

L Mankowitz 1, V M Castro 1, B Mannervik 1, J Rydström 1, J W DePierre 1
PMCID: PMC1136624  PMID: 2154179

Abstract

The effect of hypophysectomy and subsequent treatment with adrenocorticotropic hormone (adrenocorticotropin, ACTH) on the isoenzymes of glutathione transferase in the rat adrenal gland was investigated. A large increase (approx. 11-fold) in the level of transferase subunit 4 was observed in hypophysectomized animals by immunoblotting. When the activity of glutathione transferase 4-4 was measured in adrenal cytosol using trans-stilbene oxide as a selective substrate, a 15-fold increase was noted. Lack of the pituitary hormone ACTH is apparently related to this increase, since treatment of hypophysectomized animals with ACTH for 2 weeks partially down-regulated subunit 4. Glutathione transferase subunits 3 and 8 in the adrenal were also increased in amount by hypophysectomy, but not at all to the same extent. The activity of glutathione transferase 4-4 was elevated also in the liver and ovary (5 and 1.5 times respectively) after hypophysectomy. These elevated enzyme levels were, however, not affected by ACTH treatment. This down-regulation of glutathione transferases in the rat adrenal by ACTH may be related to the fact that, under normal conditions, this organ is highly susceptible to the toxic effects of various polycyclic hydrocarbons, whereas under circumstances where there is no ACTH production, as in hypophysectomized rats, the adrenal is resistant to these same hydrocarbons.

Full text

PDF
147

Images in this article

149Fig. 1.
on p.149
150Fig. 2.
on p.150
152Fig. 4.
on p.152

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alin P., Jensson H., Guthenberg C., Danielson U. H., Tahir M. K., Mannervik B. Purification of major basic glutathione transferase isoenzymes from rat liver by use of affinity chromatography and fast protein liquid chromatofocusing. Anal Biochem. 1985 May 1;146(2):313–320. doi: 10.1016/0003-2697(85)90545-7. [DOI] [PubMed] [Google Scholar]
  2. Bengtsson M., Montelius J., Mankowitz L., Rydström J. Metabolism of polycyclic aromatic hydrocarbons in the rat ovary. Comparison with metabolism in adrenal and liver tissues. Biochem Pharmacol. 1983 Jan 1;32(1):129–136. doi: 10.1016/0006-2952(83)90664-0. [DOI] [PubMed] [Google Scholar]
  3. Berzins K., Wahlgren M., Perlmann P. Studies on the specificity of anti-erythrocyte antibodies in the serum of patients with malaria. Clin Exp Immunol. 1983 Nov;54(2):313–318. [PMC free article] [PubMed] [Google Scholar]
  4. Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
  5. Carlberg I., Altmejd B., Mannervik B. Purification and immunological studies of glutathione reductase from rat liver. Evidence for an antigenic determinant at the nucleotide-binding domain of the enzyme. Biochim Biophys Acta. 1981 Sep 18;677(1):146–152. doi: 10.1016/0304-4165(81)90156-2. [DOI] [PubMed] [Google Scholar]
  6. Eidne K. A., Bass N. M., Sherman M., Millar R. P., Kirsch R. E. Ligandin concentrations in the steroidogenic tissues of the rat during development. Biochim Biophys Acta. 1984 Oct 16;801(3):424–428. doi: 10.1016/0304-4165(84)90148-x. [DOI] [PubMed] [Google Scholar]
  7. Faulder C. G., Hirrell P. A., Hume R., Strange R. C. Studies of the development of basic, neutral and acidic isoenzymes of glutathione S-transferase in human liver, adrenal, kidney and spleen. Biochem J. 1987 Jan 1;241(1):221–228. doi: 10.1042/bj2410221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gill S. S., Ota K., Hammock B. D. Radiometric assays for mammalian epoxide hydrolases and glutathione S-transferase. Anal Biochem. 1983 May;131(1):273–282. doi: 10.1016/0003-2697(83)90166-5. [DOI] [PubMed] [Google Scholar]
  9. Guenthner T. M., Nebert D. W., Menard R. H. Microsomal aryl hydrocarbon hydroxylase in rat adrenal: regulation by ACTH but not by polycyclic hydrocarbons. Mol Pharmacol. 1979 May;15(3):719–728. [PubMed] [Google Scholar]
  10. HUGGINS C., MORII S. Selective adrenal necrosis and apoplexy induced by 7, 12-dimethylbenz(a)anthracene. J Exp Med. 1961 Nov 1;114:741–760. doi: 10.1084/jem.114.5.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Habig W. H., Pabst M. J., Jakoby W. B. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974 Nov 25;249(22):7130–7139. [PubMed] [Google Scholar]
  12. Hallberg E., Rydström J. Toxicity of 7,12-dimethylbenz[a]anthracene and 7-hydroxymethyl-12-methylbenz[a]anthracene and its prevention in cultured rat adrenal cells. Evidence for a peroxidative mechanism of action. Toxicology. 1987 Dec 14;47(3):259–275. doi: 10.1016/0300-483x(87)90056-4. [DOI] [PubMed] [Google Scholar]
  13. Hatayama I., Satoh K., Sato K. Developmental and hormonal regulation of the major form of hepatic glutathione S-transferase in male mice. Biochem Biophys Res Commun. 1986 Oct 30;140(2):581–588. doi: 10.1016/0006-291x(86)90771-0. [DOI] [PubMed] [Google Scholar]
  14. Hornsby P. J., Crivello J. F. The role of lipid peroxidation and biological antioxidants in the function of the adrenal cortex. Part 2. Mol Cell Endocrinol. 1983 May;30(2):123–147. doi: 10.1016/0303-7207(83)90043-6. [DOI] [PubMed] [Google Scholar]
  15. Ketterer B. Detoxication reactions of glutathione and glutathione transferases. Xenobiotica. 1986 Oct-Nov;16(10-11):957–973. doi: 10.3109/00498258609038976. [DOI] [PubMed] [Google Scholar]
  16. Kraus P., Kloft H. D. The activity of glutathione-S-transferases in various organs of the rat. Enzyme. 1980;25(3):158–160. doi: 10.1159/000459242. [DOI] [PubMed] [Google Scholar]
  17. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  18. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  19. Mannervik B., Alin P., Guthenberg C., Jensson H., Tahir M. K., Warholm M., Jörnvall H. Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7202–7206. doi: 10.1073/pnas.82.21.7202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mannervik B., Danielson U. H. Glutathione transferases--structure and catalytic activity. CRC Crit Rev Biochem. 1988;23(3):283–337. doi: 10.3109/10409238809088226. [DOI] [PubMed] [Google Scholar]
  21. Mannervik B. The isoenzymes of glutathione transferase. Adv Enzymol Relat Areas Mol Biol. 1985;57:357–417. doi: 10.1002/9780470123034.ch5. [DOI] [PubMed] [Google Scholar]
  22. Meyer D. J., Ketterer B. 5 alpha,6 alpha-Epoxy-cholestan-3 beta-ol (cholesterol alpha-oxide): A specific substrate for rat liver glutathione transferase B. FEBS Lett. 1982 Dec 27;150(2):499–502. doi: 10.1016/0014-5793(82)80798-9. [DOI] [PubMed] [Google Scholar]
  23. Montelius J., Papadopoulos D., Bengtsson M., Rydström J. Metabolism of polycyclic aromatic hydrocarbons and covalent binding of metabolites to protein in rat adrenal gland. Cancer Res. 1982 Apr;42(4):1479–1486. [PubMed] [Google Scholar]
  24. Rahimtula A. D., Zachariah P. K., O'Brien P. J. Differential effects of antioxidants, steroids and other compounds on benzo(a)pyrene 3-hydroxylase activity in various tissues of rat. Br J Cancer. 1979 Jul;40(1):105–112. doi: 10.1038/bjc.1979.146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Simpson E. R., Waterman M. R. Regulation by ACTH of steroid hormone biosynthesis in the adrenal cortex. Can J Biochem Cell Biol. 1983 Jul;61(7):692–707. doi: 10.1139/o83-088. [DOI] [PubMed] [Google Scholar]
  26. Simpson E. R., Waterman M. R. Regulation of the synthesis of steroidogenic enzymes in adrenal cortical cells by ACTH. Annu Rev Physiol. 1988;50:427–440. doi: 10.1146/annurev.ph.50.030188.002235. [DOI] [PubMed] [Google Scholar]
  27. Warholm M., Guthenberg C., Mannervik B. Molecular and catalytic properties of glutathione transferase mu from human liver: an enzyme efficiently conjugating epoxides. Biochemistry. 1983 Jul 19;22(15):3610–3617. doi: 10.1021/bi00284a011. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES