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.

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 microM) 25-OH-cholesterol stimulated the aldosterone production in a (not-linear) dose-dependent way. An increase in the 22S-OH-cholesterol concentration from 25 microM to 50 microM 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 potassium-induced 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.