A novel compound, NO-1886, which possesses a powerful lipoprotein lipase activity-increasing action, induces hypertrophy of adrenals in rats and hyperplasia of cortical cells in dogs. However, these effects were not observed in monkeys. We examined the effects of NO-1886 on steroid hormone production by adrenocortical cells to clarify its effects on adrenal steroidogenesis. NO-1886 did not inhibit the steroid synthetic enzymes, including 3β-hydroxysteroid dehydrogenase, 21-hydroxylase, 11β-hydroxylase, or cholesterol side-chain cleavage enzymes. However, NO-1886 affected steroid production from adrenocortical cells in rats, dogs, monkeys, and humans in in vitro studies. These effects were almost completely reversed by the addition of 25-hydroxycholesterol or low-density lipoproteins to the reaction medium, but not reversed by the addition of high-density lipoproteins. These results suggest that NO-1886 affects the cholesterol pathways within the adrenocortical cells and inhibits steroidogenesis, causing a reduction of steroid hormone release from adrenocortical cells and resulting in hypertrophy of adrenals via feed-back mechanisms. However, its effect is not apparent in animals that use low-density lipoproteins as a source of adrenocortical steroidogenesis.
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