Effect of a cholesterol synthesis inhibitor (BM 15.766) in the presence and absence of HDL on corticosteroidogenesis of isolated zona glomerulosa and fasciculata cells.
The effect of the cholesterol synthesis inhibitor BM 15.766, 4-[2-[1-(4-chlorocinamyl)piperazin-4-yl]ethyl]-benzoic acid on the corticosteroid production was studied in order to reveal the importance of endogenous cholesterol synthesis in the function of zona glomerulosa and zona fasciculata cells of rats. Attempts were made to compensate the effect of BM 15.766 through the application of high-density lipoproteins (HDL). Electron microscopy was used to trace the binding and intracellular accumulation of colloidal gold-labelled HDL (HDL-Au, a cholesterol carrier), in the presence of the cholesterol biosynthesis inhibitor. The stimulation of both types of cells with ACTH was less effective in the presence of 2 x 10(-5) M BM 15.766. The inhibitory effect of BM 15.766 was most marked on the aldosterone production of the zona glomerulosa cells, and could not be reversed by addition of a small amount of HDL-Au. Corticosterone-aldosterone conversion was inhibited by 2 x 10(-5) M BM 15.766. ACTH-stimulated, short-term HDL uptake and internalization was not affected by the cholesterol synthesis inhibitor. The results suggest that certain metabolites of de novo cholesterol biosynthesis may participate in the control of aldosterone production.
Tóth
I E
IE
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Szalay
K S
KS
Szabó
D
D
Pill
J
J
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D008076:Cholesterol, HDL / Q000096:biosynthesis*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D015383:Zona Fasciculata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D010879:Piperazines; C047457:BM 15766; D000324:Adrenocorticotropic Hormone