Conversion of 22S-hydroxy-cholesterol and its effect on the metabolism of other sterols in rat adrenal cells and bovine adrenal mitochondria

1982 ◽  
Vol 100 (4) ◽  
pp. 599-605 ◽  
Author(s):  
J. G. M. Huijmans ◽  
H. J. Degenhart ◽  
D. J. Kortleve
Keyword(s):  
Causal Relationship ◽  
Enzyme System ◽  
Inhibitory Effect ◽  
Side Chain ◽  
Steroid Production ◽  
Adrenal Cell ◽  
Adrenal Cells ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Isolated Rat

Abstract. This study provides evidence that 22S-OH-cholesterol inhibits the conversion of 25-OH-cholesterol but has no effect on the conversion of 22R-OH-cholesterol. The latter sterol is an intermediate in the cholesterol side-chain cleavage, whereas for the conversion of 25-OH-cholesterol into pregnenolone the complete side-chain cleaving enzyme system is necessary. This complements a previous study in which it was shown, that 22S-OH-cholesterol has an inhibitory effect on the ACTH-induced conversion of cholesterol into corticosterone in isolated rat adrenal cells. The available evidence thus suggests an inhibition by 22S-OH-cholesterol of the first step in the cholesterol side-chain cleavage. The results, obtained from the experiments with rat adrenal cells and with bovine adrenal mitochondria, allow the hypothesis, that a causal relationship exists between conversion of 22S-OH-cholesterol and production of corticosterone, respectively pregnenolone. We conclude, that 22S-OH-cholesterol is a substrate for steroid production in the adrenal cell. This sterol inhibits the ACTH-stimulated corticosterone production. The site of this inhibition is located at one of the first steps in the cholesterol side-chain cleavage, probably the binding of cholesterol to the cytochrome P450-complex.

Effects of 22S-hydroxy-cholesterol and other hydroxylated sterols on the ACTH-stimulated steroid production in rat adrenal cells

1981 ◽  
Vol 97 (2) ◽  
pp. 243-250 ◽  
Author(s):  
J. G. M. Huijmans ◽  
H. J. Degenhart ◽  
D. J. Kortleve ◽  
H. K. A. Visser
Keyword(s):  
Cholesterol Metabolism ◽  
Cellular Membrane ◽  
Inhibitory Effect ◽  
Cholesterol Concentration ◽  
Side Chain ◽  
Steroid Production ◽  
Adrenal Cells ◽  
Chain Cleavage ◽  
Coa Reductase ◽  
Hydrolysis Of

Abstract. Several effects of hydroxylated sterols on cell cultures are known. Most of these can be explained by an inhibition of the cholesterol synthesis at the level of the 3-hydroxy-3-methylglutaryl CoA reductase. When studying cholesterol metabolism in rat adrenal cells, an inhibitory action of some sterols on the ACTH-stimulated corticosterone production was observed. The effects of one sterol, 22S-OH-cholesterol, were investigated further. The sterol had no effect on the ACTH-stimulated cyclic AMP production, suggesting an intact receptor-adenylate cyclase complex and cellular membrane. In the presence of ACTH and 22S-OH-cholesterol particularly the free cholesterol concentration was elevated; 22S-OH-cholesterol therefore probably exerts its inhibitory effect at a step located after hydrolysis of the cholesterol esters. 22S-OH-cholesterol had no effect on the conversion of exogenous pregnenolone into corticosterone. These results make it probable, that the inhibitory effect of 22S-OH-cholesterol on the ACTH-stimulated corticosterone production is situated at the level of the cholesterol side-chain cleavage.

Effects of some hydroxylated sterols on the steroid production in isolated rat adrenal glomerulosa and fasciculata/reticularis cells in the presence of potassium, angiotensin II or ACTH

1984 ◽  
Vol 105 (3) ◽  
pp. 411-416
Author(s):  
J. G. M. Huijmans ◽  
H. E. Falke ◽  
H.J. Degenhart
Keyword(s):  
Cholesterol Concentration ◽  
Side Chain ◽  
Steroid Production ◽  
Side Chain Cleavage ◽  
Rate Limiting Step ◽  
Chain Cleavage ◽  
Exogenous Substrate ◽  
Aldosterone Production ◽  
Isolated Rat

Abstract. 22S-OH-cholesterol and 25-OH-cholesterol are good aldosterone precursors in isolated rat adrenal glomerulosa cells. In the two concentrations tested (25 and 50 μm) 25-OH-cholesterol stimulated the aldosterone production in a (not-linear) dose-dependent way. An increase in the 22S-OH-cholesterol concentration from 25 μm to 50 μm led to a decrease in the aldosterone production. The exogenous substrate deoxycorticosterone, entering the steroidogenic pathway after the cholesterol side-chain cleavage, is a much better substrate than the sterols mentioned. These results suggest that the cholesterol side-chain cleavage is the rate-limiting step in the aldosterone production from both sterols. We found no effect of the sterols on the potassiuminduced aldosterone synthesis. This might be explained by the existence of separate pools of steroid intermediates within the adrenal cell. In vitro a difference in steroid production rates exists between glomerulosa and fasciculata/reticularis cells. This may arise from differences in availability of endogenous steroid precursors like cholesterol. However similar differences can be observed if exogenous substrates like 25-OH-cholesterol or 22S-OH-cholesterol are used. These results therefore suggest that enzymatic activities in the steroidogenic pathway are more important than the cholesterol concentration in regulating steroid production in isolated rat adrenal glomerulosa and fasciculata/reticularis cells.

Specificity of the cholesterol side-chain cleavage enzyme system of adrenal cortex

Steroids ◽  
1977 ◽  
Vol 30 (4) ◽  
pp. 439-453 ◽  
Author(s):  
Shlomo Burstein ◽  
R.C. Nickolson ◽  
Chang Y. Byon ◽  
Howard L. Kimball ◽  
Marcel Gut
Keyword(s):  
Adrenal Cortex ◽  
Enzyme System ◽  
Side Chain ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Cleavage Enzyme
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