Lipoprotein lipase promoting agent, NO-1886, modulates adrenal functions: species difference in effects of NO-1886 on steroidogenesis.
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 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, 11beta-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.
Shimono
K
K
Otsuka Pharmaceutical Factory, Inc., Naruto Tokushima, Japan.
Tsutsumi
K
K
Yaguchi
H
H
Omura
M
M
Sasano
H
H
Nishikawa
T
T
D000302:Adrenal Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D004285:Dogs; D004789:Enzyme Activation; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008252:Macaca fascicularis; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D000305:Adrenal Cortex Hormones; D001549:Benzamides; D009943:Organophosphorus Compounds; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; D008071:Lipoprotein Lipase