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Changes in the adrenal cortex of the rat after chronic administration of the steroidogenic inhibitor U-8113

Cell and Tissue Research volume 190, pages 123–134 (1978)Cite this article

Summary

In concert with studies of the effects of various pharmacologic inhibitors of corticosteroidogenesis on adrenocortical morphology, U-8113, an analog of amphenone B, was administered daily to Sprague-Dawley rats for 7, 14, 21 or 30 days. The primary morphological responses involved increases in adrenal weight, width of zona fasciculata, width of zona reticularis, intracellular lipids, mitochondrial size, mitochondrial vacuolation and crystalline-like inclusions, small coated vesicles, lysosomes, autophagic vacuoles and cholesterol ester clefts. In particular, the increases in lysosomes, coated vesicles and autophagic vacuoles containing morphologically altered mitochondria were considered reflective of mechanisms designed to maintain cellular integrity amidst functional impairment. Lipid analysis revealed marked increases in cholesterol esters and phospholipids, supportive of morphological observations. When permitted a 14 day recovery period following either 14 or 30 days of inhibitor therapy, most fine structural alterations and lipid derangements were diminished, and the cells approximated normal parameters.

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Affiliations

  1. Departments of Anatomy, Oral Biology and Cell and Molecular Biology, Schools of Dentistry and Medicine, Medical College of Georgia, Augusta, Georgia, USA

    Mohamed Sharawy, David P. Penney, Thomas R. Dirksen & Kathy Averill

  2. Department of Anatomy, School of Medicine and Dentistry, University of Rochester, Rochester, New York, USA

    Mohamed Sharawy, David P. Penney, Thomas R. Dirksen & Kathy Averill

Authors
  1. Mohamed Sharawy
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  2. David P. Penney
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  3. Thomas R. Dirksen
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  4. Kathy Averill
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Additional information

Supported in part by USPHS Grant, AM-09561 to D.P.P.; by scholarships and research support to M.S. from Institute of International Education, UAR Education Bureau and the Department of Dentistry and Dental Research, University of Rochester; and by USPHS Grant GN-13002 to T.R.D.

Portions of this work have been presented in abstract form at the American Association of Anatomists Meetings

The authors are grateful to Miss Anne E. Cannady for her technical help in the biochemical part of this study, and to Dr. Edwin D. Bransome, Jr. for valuable criticism in the final preparation of this manuscript. U-8113 was generously provided by Dr. Paul W. O'Connell of The Upjohn Company

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Sharawy, M., Penney, D.P., Dirksen, T.R. et al. Changes in the adrenal cortex of the rat after chronic administration of the steroidogenic inhibitor U-8113. Cell Tissue Res. 190, 123–134 (1978). https://doi.org/10.1007/BF00210042

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  • DOI: https://doi.org/10.1007/BF00210042

Key words

  • Adrenal
  • Steroidogenesis
  • Inihibitor
  • Ultrastructure