Induction of steroidogenic enzyme genes by insulin and IGF-I in cultured adult human adrenocortical cells

Sonja B. Kristiansen, Akira Endoh, Peter R. Casson, John E. Buster, Peter J. Hornsby

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Insulin and the insulin-like growth factors (IGFs) have multiple roles in gene expression in steroidogenic cells. We investigated the regulation of steroidogenic enzyme gene expression by insulin and IGF-I in primary cultures of human adrenocortical cells from donors of ages 19-77 years. The effects of insulin and IGF-I observed here, were independent of age and sex of the donor. After 5 days in serum-containing medium, cultures were exposed to insulin or IGF-I together- with cyclic AMP analogs or ACTH in serum-free defined medium. Insulin and IGF-I at physiological concentrations increased mRNA levels for 17α-hydroxylase and type II 3β-hydroxysteroid dehydrogenase (3β-HSD) in the absence of cyclic AMP or ACTH. They had lesser effects on 21-hydroxylase and cholesterol side-chain cleavage enzyme mRNA levels and were without effect on 11β-hydroxylase mRNA. All steroidogenic enzyme mRNAs were strongly increased by cyclic AMP or ACTH, and this increase was potentiated by insulin or IGF-I. These effects of insulin and IGF-I were accompanied by decreases in the ratio of dehydroepiandrosterone/cortisol synthesized from pregnenolone by the cultures. Induction of steroidogenic enzyme genes in adult human adrenocortical cells by insulin and IGF-I is unlikely to occur by means of a cyclic AMP-dependent mechanism. These data increase the evidence for an important regulation of steroidogenesis by these hormones.

Original languageEnglish (US)
Pages (from-to)258-265
Number of pages8
JournalSteroids
Volume62
Issue number2
DOIs
StatePublished - Feb 1997
Externally publishedYes

Keywords

  • IGF-I
  • aging
  • human adrenocotical cell
  • insulin
  • steroidogenic enzyme gene

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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