Skip to main content
SpringerLink
Log in

Chemically Induced Adrenocortical Degenerative Lesions

  • Chapter
Endocrine System

Part of the book series: Monographs on Pathology of Laboratory Animals ((LABORATORY))

Abstract

Adrenocortical degenerative lesions can be induced by a wide range of structurally dissimilar and functionally unrelated compounds. A review of the literature indicates that the adrenal gland, particularly the cortex, is the endocrine organ most frequently affected by chemical injury (Ribelin 1984; Colby 1988). Examples of prototype adrenotoxicants associated with adrenocortical degeneration include glucocorticoids (Sasano et al. 1966; Purjesz et al. 1964), 7,12-dimethylbenzanthracene (Murad et al. 1973), aminoglutethimide (Camacho et al. 1967; Malendowicz 1972), spironolactone (Fischer and Horvat 1971), 2,2-bis (parachlorophenyl)-l,l dichlorethane (o,p’-DDD; Nelson and Woodward 1949; Hennigar et al. 1964), α-(l,4-dioxido-3-methyl-quinoxalin-2-yl)-N-methylnitrone (DMNM; Yarrington et al. 1981, 1985; Capen et al. 1991), amphenone (Hertz et al. 1955), and 1,1’ thiodiethylidene-ferrocene (MDL 80,478; Capen et al. 1991; Yarrington et al. 1983). With many of these compounds degenerative changes in the adrenal cortex occur, in conjunction with functional alterations in steroidogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abbott EC, Monkhouse FC, Steiner JW, Laidlaw JC (1966) Effect of a sulfated mucopolysaccharide (R01-8307) on the zona glomerulosa of the rat adrenal gland. Endocrinology 78:651–654

    Article  PubMed  CAS  Google Scholar 

  • Brogan WC, Eacho PI, Hinton DE, Colby HD (1984) Effects of carbon tetrachloride on adrenocortical structure and function in guinea pigs. Toxicol Appl Pharmacol 75:118–127

    Article  PubMed  CAS  Google Scholar 

  • Camacho AM, Cash R, Brough AJ, Wilroy RS (1967) Inhibition of adrenal steroidogenesis by amino-glutethimide and the mechanism of action. JAMA 202:114–120

    Article  CAS  Google Scholar 

  • Capen CC, DeLellis RA, Yarrington JT (1991) Endocrine system. In: Haschek-Hock WM Rousseaux CG(eds) Handbook of toxicologic pathology. Academic, Orlando, pp 675–759

    Google Scholar 

  • Cohen MP (1968) Aminoglutethimide inhibition of adrenal desmolase activity. Proc Soc Exp Biol Med 127:1086–1090

    PubMed  CAS  Google Scholar 

  • Colby HD (1988) Adrenal gland toxicity: chemically induced dysfunction. J Am Coll Toxicol 7:45–69

    Article  CAS  Google Scholar 

  • Colby HD, Pope MR, Johnson PB, Sherry JH (1987) Effects of cadmium in vitro on microsomal steroid metabolism in the inner and outer zones of the guinea pig adrenal cortex. J Biochem Toxicol 2:1–11

    Article  PubMed  CAS  Google Scholar 

  • Currie AR, Helfenstein JE, Young S (1962) Massive adrenal necrosis in rats caused by 9,10-dimethyl-l,2-benzanthracene and its inhibition by metyrapone. Lancet ii: 1199–1200

    Article  Google Scholar 

  • Dexter RN, Fishman LM, Ney RL, Liddle GW (1967) Inhibition of adrenal corticosteroid synthesis by aminoglutethimide: Studies of the mechanism of action. J Clin Endocrinol Metab 27:473–480

    Article  PubMed  CAS  Google Scholar 

  • Dietert SE, Scallen TJ (1969) An ultrastructural and biochemical study of the effects of three inhibitors of cholesterol biosynthesis upon murine adrenal gland and testis. J Cell Biol 40:44–60

    Article  PubMed  CAS  Google Scholar 

  • Dominick MA, Bobrowski WA, MacDonald JR, Gough AW (1993a) Morphogenesis of a zone-specific adrenocortical cytotoxicity in guinea pigs administered PD 132301-2, an inhibitor of acyl-CoA: cholesterol acyltransferase. Toxicol Pathol 21:54–62

    Article  PubMed  CAS  Google Scholar 

  • Dominick MA, McGuire EJ, Reindel JF, Bobrowski WF, Bocan TMA, Gough AW (1993b) Subacute toxicity of a novel inhibitor of acyl-CoA: cholesterol acyltransferase in beagle dogs. Fundam Appl Toxicol 20:217–224

    Article  PubMed  CAS  Google Scholar 

  • Eacho I, Colby HD (1983) Regional distribution of microsomal drug and steroid metabolism in the guinea pig adrenal cortex. Life Sci 32:1119–1127

    Article  PubMed  CAS  Google Scholar 

  • Fisher ER, Horvat B (1971) Experimental production of socalled spironolactone bodies. Arch Pathol 91:471–478

    PubMed  CAS  Google Scholar 

  • Hallberg E (1990) Metabolism and toxicity of xenobiotics in the adrenal cortex with particular reference to 7,12-dimethylbenz(a)anthracene. J Biochem Toxicol 5:71–90

    Article  PubMed  CAS  Google Scholar 

  • Hart MM, Swackhamer ES, Straw JA (1971) Studies on the site of action of o,p’-DDD in the dog adrenal cortex. II. TPNH- and corticosteroid precursor-stimulation of o,p’-DDD-inhibited steroidogenesis. Steroids 17:575–586

    Article  PubMed  CAS  Google Scholar 

  • Hennigar GR, Fleckner RA, Golding MR (1964) Degeneration and regeneration of the adrenal cortex following administration of DDD (2,2-bis (parachlorophenyl)-l,l dichlorethane. Bull N Y Acad Med 40:161–166

    CAS  Google Scholar 

  • Hertz R, Tullner WW, Schricker JA, Dhyse FG, Hallman LF (1955) Studies on amphenone and related compounds. Recent Prog Horm Res 11:119–147

    Google Scholar 

  • Holloszy J, Eisenstein AB (1961) Effect of triparanol (MER/ 29) on corticosterone secretion by rat adrenals. Proc Soc Exp Biol Med 107:347–349

    PubMed  CAS  Google Scholar 

  • Hornsby PJ (1989) Steroid and xenobiotic effects on the adrenal cortex: mediation by oxidative and other mechanisms. Free Radic Biol Med 6:103–115

    Article  PubMed  CAS  Google Scholar 

  • Kaminsky N, Luse S, Hartroft P (1962 ) Ultrastructure of adrenal cortex of the dog during treatment with DDD. J Natl Cancer Inst 29:127–159

    PubMed  CAS  Google Scholar 

  • Liddle GW (1974) The adrenal cortex. In: Williams RH (ed) Textbook of endocrinology. Saunders, Philadelphia, pp 233–283

    Google Scholar 

  • Luse S (1967) Fine structure of the adrenal cortex. In: Eisenstein AB (ed) The adrenal cortex. Little Brown, Boston, pp 1–69

    Google Scholar 

  • Malendowicz LK (1972) Steatotic degeneration of rat adrenocortical cells after treatment with aminoglutethimide. Acta Histochem (Jena) 43:350–360

    CAS  Google Scholar 

  • Marek J, Pfeifer U (1971) Microthrombi as a partial cause of adrenal damage due to hexadimethrine bromide (Polybrene). Verh Dtsch Ges Pathol 55:706–709

    PubMed  CAS  Google Scholar 

  • Marek J, Pfeifer U, Motlik K (1973) Ultrastructure of the protein-containing vacuoles and hyaline droplets in rat adrenocortical cells following Polybrene. Virchows Arch B Cell Pathol 14:273–283

    PubMed  CAS  Google Scholar 

  • Mitani F (1979) Cytochrome P450 in adrenocortical mitochondria. Mol Cell Biochem 24:21–44

    Article  PubMed  CAS  Google Scholar 

  • Mohammed A, Hallberg E, Rydstrom J, Slanina P (1985) Toxaphene: accumulation in the adrenal cortex and effect on ACTH-stimulated corticosteroid synthesis in the rat. Toxicol Lett 24:137–143

    Article  PubMed  CAS  Google Scholar 

  • Moore NA, Callas G (1975) Observations on the fine structure of propylthiouracil-induced “brown degeneration” in the zona reticularis of mouse adrenal cortex. Anat Rec 183: 293–302

    Article  PubMed  CAS  Google Scholar 

  • Murad TM, Leibach J, Von Hamm E (1973) Latent effect of DMBA on adrenal glands of Sprague-Dawley rats: an ultrastructural study. Exp Mol Pathol 18:305–315

    Article  PubMed  CAS  Google Scholar 

  • Nelson AA, Woodward G (1949) Severe adrenal cortical atrophy (cytotoxic) and hepatic damage produced in dogs by feeding 2,2-bis (parachlorophenyl)-1,1-dichlorethane (DDD or TDE). Arch Pathol 48:387–394

    CAS  Google Scholar 

  • Powers JM, Hennigar GR, Grooms G, Nichols J (1974) Adrenal cortical degeneration and regeneration following administration of DDD. Am J Pathol 75:181–194

    PubMed  CAS  Google Scholar 

  • Purjesz I, Sturcz J, Huttner I (1964) The effect of chronic prolonged water loading on prednisolone induced adrenocortical atrophy. Experimentia 20:688–689

    Article  CAS  Google Scholar 

  • Racela A Jr, Azarnoff D, Svoboda D (1969) Mitochondrial cavitation and hypertrophy in rat adrenal cortex due to aminoglutethimide. Lab Invest 21:52–60

    PubMed  Google Scholar 

  • Reindel JF, Dominick MA, Krause B (1992) Comparative adrenotoxicity of a novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor (PD 132301-2) in laboratory animals. Toxicol Pathol 20:A642

    Article  Google Scholar 

  • Reindel JF, Dominick MA, Bocan TM, Gough AW, McGuire EJ (1994) Toxicologic effects of a novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor in cynomolgus monkeys. Toxicol Pathol 22:510–518

    Article  PubMed  CAS  Google Scholar 

  • Rhodin JA (1971) The ultrastructure of the adrenal cortex of the rat under normal and experimental conditions. J Ultrastruct Res 34:23–71

    Article  PubMed  CAS  Google Scholar 

  • Ribelin WE (1984) The effects of drugs and chemicals upon the structure of the adrenal gland. Fundam Appl Toxicol 4:105–109

    Article  PubMed  CAS  Google Scholar 

  • Sasano N, Ichinoe F, Hirano K (1966) Histological and enzyme histochemical studies on adrenocortical atrophy induced by hydrocortisone, dexamethasone and paramethasone. Nippon Naibunpi Gakkai Zasshi 41:1432–1437

    PubMed  CAS  Google Scholar 

  • Steinberg D, Avigan J (1960) Studies of cholesterol biosynthesis. II. The role of desmosterol in the biosynthesis of cholesterol. J Biol Chem 235:3127–3129

    CAS  Google Scholar 

  • Szabo S, Lippe IT (1989) Adrenal gland: chemically induced structural and functional changes in the cortex. Toxicol Pathol 17:317–329

    Article  PubMed  CAS  Google Scholar 

  • Temple TE, Liddle GW (1970) Inhibitors of adrenal steroid biosynthesis. Annu Rev Pharmacol 10:199–218

    Article  PubMed  CAS  Google Scholar 

  • Vilar O, Tullner WW (1959) Effects of o,p’-DDD on histology and 17-hydroxycorticosteroid output of the dog adrenal cortex. Endocrinology 65:80–86

    Article  PubMed  CAS  Google Scholar 

  • Volk TL, Scarpelli DG (1964) Alterations of fine structure of the rat adrenal cortex after the administration of triparanol. Lab Invest 13:1205–1214

    PubMed  CAS  Google Scholar 

  • Yarrington JT, Huffman KW, Gibson JP (1981) Adrenocortical degeneration in dogs, monkeys and rats treated with α-(l,4-dioxido-3-methylquinoxalin-2-yl)-N-methylnitrone. Toxicol Lett 8:229–234

    Article  PubMed  CAS  Google Scholar 

  • Yarrington JT, Huffman KW, Leeson GA, Sprinkle DJ, Loudy DE, Gibson JP (1983) Comparative toxicity of the hematinic MDL 80,478 - effects on the liver and adrenal cortex of the dog, rat and monkey. Fundam Appl Toxicol 3:86–94

    Article  PubMed  CAS  Google Scholar 

  • Yarrington JT, Loudy DE, Sprinkle DJ, Gibson JP, Wright GL, Johnston JO (1985) Degeneration of the rat and canine adrenal cortex caused by α-(l,4-dioxido-3-methylquinoxalin-2-yl)-N-methylnitrone (DMNM). Fundam Appl Toxicol 5:370–381

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Battelle Memorial Institute, Comlumbus, Ohio, USA

    John T. Yarrington D.V.M., Ph.D. (Pathologist)

  2. Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co, Ann Arbor, Michigan, USA

    James F. Reindel D.V.M., Ph.D. (Staff Pathologist/Senior Research Associate)

Authors
  1. John T. Yarrington D.V.M., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James F. Reindel D.V.M., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. ILSI Research Foundation, Harvard Medical School, 1126 Sixteenth Street, N.W., Washington, DC, 20036, USA

    Thomas Carlyle Jones D.V.M., D.Sc. (Professor of Comparative Pathology, Emeritus) (Professor of Comparative Pathology, Emeritus)

  2. Department of Veterinary Biosciences, Department of Internal Medicine, College of Medicine, The Ohio State University, 1925 Coffey Road, Columbus, OH, 43210-1093, USA

    Charles C. Capen D.V.M., Ph.D. (Professor of Veterinary Pathobiology and Chairman, Professor of Endocrinology) (Professor of Veterinary Pathobiology and Chairman, Professor of Endocrinology)

  3. Institut für Experimentelle Pathologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Strasse 8, 30625, Hannover, Germany

    Ulrich Mohr M.D. (Professor of Experimental Pathology) (Professor of Experimental Pathology)

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Yarrington, J.T., Reindel, J.F. (1996). Chemically Induced Adrenocortical Degenerative Lesions. In: Jones, T.C., Capen, C.C., Mohr, U. (eds) Endocrine System. Monographs on Pathology of Laboratory Animals. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60996-1_63

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-60996-1_63

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64649-2

  • Online ISBN: 978-3-642-60996-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation