Lipoprotein lipase promoting agent, NO-1886, modulates adrenal functions: Species difference in effects of NO-1886 on steroidogenesis

Kazuyuki Shimono, Kazuhiko Tsutsumi, Hiroshi Yaguchi, Masao Omura, Hironobu Sasano, Tetsuo Nishikawa

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)453-459
Number of pages7
JournalSteroids
Volume64
Issue number7
DOIs
Publication statusPublished - 1999 Jul 1

Keywords

  • 25-Hydroxycholesterol
  • Adrenocortical cell
  • High density lipoprotein
  • Hypertrophy
  • Low density lipoprotein
  • Steroidogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

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