Summary
The effects of a 7-day administration of aminoglutethimide (AG) on the adrenal zona fasciculata were examined in “normal” and dexamethasone/ACTH-treated rats. There was a 70–74% decrease in the concentration of corticosterone in blood, but no conspicuous qualitative changes suggesting cell degeneration occurred. Morphometry showed that AG induced a significant hypertrophy of the zona fasciculata and its parenchymal cells only in “normal” animals, which was due to an increase in the volume of the mitochondrial compartment and to proliferation of the smooth endoplasmic reticulum. This response to AG was considered to be non-specific and mediated by the enhanced secretion of ACTH following the decrease in the blood level of corticosterone. AG administration significantly increased the volume of the lipid-droplet compartment and the number of intramitochondrial lipid-like inclusions in both groups of animals. These changes were interpreted as the morphological counterpart of the AG-induced block of cholesterol utilization in steroid synthesis.
Similar content being viewed by others
References
Bliss CI (1967) Statistic in biology, Vol 1. McGraw-Hill, New York
Boyd GS, McNamara B, Suckling KE, Tocher DR (1983) Cholesterol metabolism in the adrenal cortex. J Steroid Biochem 19:1017–1027
Chung KW (1982) Effect of aminoglutethimide on the structure and function of rat adrenals. Res Commun Chem Pathol Pharmacol 37:215–226
Civen M, Leeb J, Hill M, Sekhon S (1984) Effects of excess dietary cholesterol on adrenal cholesterol accumulation and steroidogenesis. J Steroid Biochem 20:893–899
Cohen MNP (1968) Aminoglutethimide inhibition of adrenal desmolase activity. Proc Soc Exp Biol Med 127:1086–1090
Connely OM, Meadon DR, Olson CD, Ungar F, Dempsey ME (1984) Intramitochondrial movement of adrenal sterol carrier protein with cholesterol in response to corticotropin. Proc Natl Acad Sci USA 81:2970–2974
Deacon AC, Dawson PJG (1979) Enzymatic assay of total cholesterol involving chemical or enzymic hydrolysis. A comparison of methods. Clin Chem 25:976–984
Dexter RN, Fishman LM, Ney RL, Liddle GW (1967) Inhibition of adrenal corticosteroid synthesis by aminoglutethimide: studies on the mechanism of action. J Clin Endocrinol Metab 27:473–480
Friend DS, Brassil GE (1970) Osmium staining of endoplasmic reticulum and mitochondria in the rat adrenal cortex. J Cell Biol 46:252–266
Gorgas K (1971) Über die Ultrastruktur der Zona reticularis der Nebennierenrinde vom Nutria (Myocastor coypus Molina) unter besonderer Berücksichtigung der sog. dunklen Zellen. Ergeb Anat Entwicklungsgesch 45:1–80
Gwynne JT, Strauss JF III (1982) The role of lipoproteins in steroidogenesis and cholesterol metabolism in steroidogenic glands. Endocr Rev 3:299–329
Idelman S (1978) The ultrastructure of the mammalian adrenal cortex. In: Chester-Jones I, Henderson IW (eds) General, comparative and clinical endocrinology of the adrenal cortex. Academic Press, New York, Vol 2, pp 1–199
Itoh G (1971) Electron microscopic studies on the adrenal of rat treated with aminoglutethimide, with special reference to accumulation of cholesterol in intramitochondrial vacuoles. Nagoya J Med Sci 34:183–190
Itoh G (1978) Elektronenmikroskopische und elektronenmikroskopisch-histochemische Untersuchungen über Nebennierenrinde der Ratte mit Aminoglutäthimid (Elipten, Ciba) und über ihren Reparaturprozeß. Acta Pathol Jpn 27:75–91
Kai O, Fujoka T, Yasuda M (1978) Light and electron microscopic studies of intramitochondrial bodies in bovine adrenocortical cells by proteolytic digestion. Histochemistry 57:217–221
Kai O, Fujoka T, Yasuda M (1979) Isolation of intramitochondrial bodies in bovine adrenocortical cells by density gradient centrifugation. Histochemistry 59:305–310
Loud AV (1962) A method for the quantitative estimation of cytoplasmic structures. J Cell Biol 15:481–487
Magalhães MC, Magalhães MM (1972) Ultrastructural alterations produced in rat adrenal by aminoglutethimide: a stereologic and cytochemical study. Endocrinology 90:440–452
Malendowicz LK (1972) Steatotic degeneration of rat adrenocortical cells after treatment with aminoglutethimide. Acta Histochem (Jena) 43:350–360
Marek J, Motlik K (1975) Ultrastructural changes of the adrenal cortex in Cushing's syndrome treated with aminoglutethimide (Elipten, Ciba). Virchows Arch B 18:145–156
Marek J, Motlik K (1978) Ultrastructure of acute adrenocortical damage due to aminoglutethimide (Elipten, Ciba). Virchows Arch 627:173–187
Marek J, Thoenes W, Motlik K (1970) Lipoide Transformation der Mitochondrien in Nebennierenrindenzellen nach Aminoglutäthimid (Elipten, Ciba). Virchows Arch B 6:116–131
Moore RN, Penney DP, Averill KT (1980) Fine structural and biochemical effects of aminoglutethimide and o,p′-DDD on rat adrenocortical carcinoma 494 and adrenals. Anat Rec 198:113–124
Moses HL, Davis WW, Rosenthal AS, Garren LD (1969) Adrenal cholesterol: localization by electron-microscope autoradiography. Science 163:1203–1205
Nussdorfer GG (1986) Cytophysiology of the adrenal cortex. Int Rev Cytol 98:1–405
Nussdorfer GG, Mazzocchi G (1983) Long-term effects of ACTH on rat adrenocortical cells: a coupled stereological and enzymological study. J Steroid Biochem 19:1753–1756
Paul DP, Gallant S, Orme-Johnson NR, Orme-Johnson WH, Brownie AC (1967) Temperature dependence of cholesterol binding to cytochrome P-450scc of the rat adrenal. Effect of adrenocorticotropic hormone and cycloheximide. J Biol Chem 251:7120–7126
Privalle CT, Crivello JF, Jefcoate CR (1983) Regulation of intramitochondrial cholesterol transfer to side-chain cleavage cytochrome P-450 in rat adrenal gland. Proc Natl Acad Sci USA 80:702–706
Racela A Jr, Azarnoff D, Svoboda D (1969) Mitochondrial cavitation and hypetrophy in rat adrenal cortex due to aminoglutethimide. Lab Invest 21:52–60
Rees LH, Cook DM, Kendall JW, Allen CF, Kramer RM, Ratcliffe JG, Knight RA (1971) A radioimmunoassay for rat plasma ACTH. Endocrinology 89:254–261
Sharawy M, Dirksen T, Chaffin J (1979) Increase in free cholesterol content of the adrenal cortex after stress: a radioautographic and biochemical study. Am J Anat 156:567–576
Sippell WG, Bidlingmaier F, Becker H, Brünig T, Dörr M, Golder W, Holmann G, Knorr D (1978) Simultaneous radioimmunoassay of plasma aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol and cortisone. J Steroid Biochem 9:63–74
Spady DK, Dietschy JM (1985) Rates of cholesterol synthesis and low-density lipoprotein uptake in the adrenal glands of the rat, hamster and rabbit in vivo. Biochem Biophys Acta 863:167–175
Spät A, Jozan S (1972) Competitive protein binding assay of corticosterone. J Steroid Biochem 3:755–759
Starka L, Motlik K (1971) The influence of injected aminoglutethimide on the morphology of the rat adrenal cortex and adrenal metabolism of progesterone. Endokrinologie 58:75–86
Swinyard CA (1938) Methods for volumetric determination of fresh endocrine glands. Anat Rec 74:71–78
Tamaoki BI (1973) Steroidogenesis and cell structure. Biochemical pursuit of sites of steroid synthesis. J Steroid Biochem 4:98–118
Vahouny GV, Dennis P, Chanderbhan R, Fiskum G, Noland BJ, Scallen TJ (1984) Sterol carrier protein2 (SCP2)-mediated transfer of cholesterol to mitochondrial inner membranes. Biochem Biophys Res Commun 122:509–515
Vahouny GV, Chanderbhan R, Stewart P, Tambes R, Keyeyune-Nyomby E, Fiskum G, Scallen TJ (1985) Phospholipids, sterol carrier protein2 and adrenal steroidogenesis. Biochim Biophys Acta 834:324–330
Vanek R (1965) Pouvoir freinateur de divers corticostéroides de synthèse sur la sécrétion d'ACTH. Etude comparative. Ann Endocrinol (Paris) 25:799–808
Weibel ER (1979) Stereological methods. 1. Practical methods for biological morphometry. Academic Press, New York
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Robba, C., Mazzocchi, G. & Nussdorfer, G.G. Effects of a prolonged treatment with aminoglutethimide on the zona fasciculata of rat adrenal cortex: A morphometric investigation. Cell Tissue Res. 248, 519–525 (1987). https://doi.org/10.1007/BF00216478
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00216478