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The Journal of Cell Biology, Vol 40, 44-60, Copyright © 1969 by Rockefeller University Press

ARTICLE

AN ULTRASTRUCTURAL AND BIOCHEMICAL STUDY OF THE EFFECTS OF THREE INHIBITORS OF CHOLESTEROL BIOSYNTHESIS UPON MURINE ADRENAL GLAND AND TESTIS

: Histochemical Evidence for a Lysosome Response



Scott E. Dietert 1 and Terence J. Scallen 1

1 From the Departments of Anatomy and Biochemistry, The University of New Mexico School of Medicine, Albuquerque, New Mexico 87106

Triparanol and 20,25-diazacholesterol inhibit cholesterol biosynthesis and result in the accumulation of desmosterol. AY-9944, another inhibitor, produces an accumulation of 7-dehydrocholesterol. Adult male C3H mice receive one of these drugs intraperitoneally. Livers, adrenal glands, and testes from each drug group are excised, and portions of each are analyzed by a modified Liebermann-Burchard reaction for quantitation of sterols. Adrenals and testes are examined also by electron microscopy. Fine-structural localization of acid phosphatase has been studied in triparanol-treated adrenal glands. Biochemical analysis reveals that 14–64% of the sterols occurs as desmosterol or 7-dehydrocholesterol. Fine-structural alterations in the adrenal glands and testes from each drug group are essentially identical. The predominant cytological feature is the occurrence of increased numbers of pleomorphic, unit-membrane-limited, electron-opaque, cytoplasmic inclusions. Hence, the cellular modifications following triparanol administration are not unique, as has been suggested. They represent a generalized phenomenon, probably related to inhibition of cholesterol biosynthesis, which is an effect common to each drug. Lead phosphate reaction product (indicating acid phosphatase activity) is demonstrable within these membrane-limited cytoplasmic bodies, identifying them as morphological lysosomes. The utilization of a lysosomal mechanism in sterol-synthesizing cells, which are accumulating cholesterol intermediates, is discussed.

Submitted on May 31, 1968
Revised on August 7, 1968


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