An Ultrastructural and Biochemical Study of the Effects of Three Inhibitors of Cholesterol Biosynthesis Upon Murine Adrenal Gland and Testis

Abstract

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 cholestercl intermediates, is discussed.

Ultrastructural and biochemical study of the action of benzoctamine and maprotiline on the rat liver

“…ER, lysosomes) with which myeloid body-inducing agents may interact cannot yet be defined [3,19,55,73,98] there is almost unanimous agreement that myeloid bodies are adjoined to the lysosomal structures [36,55,98,103]. This assignment is mainly based on histochemical evidence indicating that myeloid bodies may display acid phosphatase activity [2,25,33,75,126]. Our histochemical findings agree with these claims.…”

Circadian Rhythm of Acid Phosphatase in Mouse Testis Lysosomes

“…In the hamster, mating produces a depression of testicular acid phosphatase (Burgos, Vitale-Calpe & Russo, 1968) and causes liberation of luteinizing hormone (lh) by the hypophysis (Donoso & Santolaya, 1969). In this animal, the lh and hcg also produce a depression of the acid phosphatase (Russo & Burgos, 1970, unpublished observation In the Leydig cell, the function of the lysosomes is thought to be related to some step of steroid synthesis, as might be inferred from the results of Dietert & Scallen (1969) and Frank & Christensen (1968).…”

Specific Lamellar Structures of Agranular Endoplasmic Reticulum in the Senile Mouse Adrenal Cortex

“…Occurrence of electron-dense materials within the cisternae of SER in steroidsynthesing cells has been reported in the adrenal gland (DIETERT and SCALLEN, 1969) and testis (DIETERT and SCALLEN, 1969;RUSSO, 1971) of rats and mice following administration of triparanol, inhibitor of cholesterol synthesis, and interpreted as an accumulation of cholesterol precursor (RUSSO, 1971). Thus, it is conceivable that the electron-dense material retained in the lamellar, flattened cisternae observed in the present work might also be a substance produced during cholesterol synthesis under some inhibitory condition of SER-associated enzymatic activity, and that the lamellar structures might have been caused by accumulation of such substance into the flattened cisternae probably formed by a process of apposition and fusion of tubules of the surrounding SER.…”