Effect of the adrenal inhibitor trilostane on the morphology of the adrenocortical cells of Dahl salt-sensitive and Dahl salt-resistant rats.
The effects of trilostane on the adrenal cortex of Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats were investigated morphometrically, histochemically, ultrastructurally and biochemically. The statistical analysis indicated that trilostane induced a significant increase in the adrenal weight and the surface area of cells and nuclei in the zona fasciculata (ZF) of the adrenal cortex of DS and DR rats (P less than O.OI). DS rats treated with trilostane revealed marked accumulation of large amounts of lipid droplets and a decrease in the activity of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in the ZF. Ultrastructurally, the mitochondria of the ZF in DS rats treated with trilostane revealed swelling of matrix with a loss of cristae and occasional interruption of the membranes of mitochondria. Some of them had a continuity with lipid vacuoles or SER, presenting a characteristic 'feather'-like appearance. Other characteristic findings in DS rats treated with trilostane were a marked villous proliferation of plasma membranes with numerous dense bodies, occasional coated pits, and pinocytic vesicles in the outer portion of the ZF. In DS and DR rats the plasma level of ACTH increased, and corticosterone decreased significantly (P less than O.OI) after treatment with trilostane. These morphological alterations were considered to be an expression of the inhibitory effects of trilostane on the adrenal steroidogenesis in DS and DR rats, more especially in DS rats. Simultaneously there were confirmed morphological alterations in the cells of the ZF, reflecting the feedback stimulation of endogenous ACTH. The cells of the ZF of DS rats were more responsive to suppression by trilostane than those of DR rats.
Kawai
K
K
Department of Pathology, Nagasaki University School of Medicine, Japan.
Baba
K
K
Senba
M
M
Nakamura
T
T
Doi
Y
Y
Yamaguchi
T
T
Hashiba
K
K
Tsuchiyama
H
H
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000302:Adrenal Cortex / Q000187:drug effects* / Q000648:ultrastructure; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006973:Hypertension / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D013196:Dihydrotestosterone; D000324:Adrenocorticotropic Hormone; D015096:3-Hydroxysteroid Dehydrogenases; C009954:trilostane; D003345:Corticosterone