Induction of steroidogenic enzyme genes by insulin and IGF-I in cultured adult human adrenocortical cells.
Insulin and the insulin-like growth factors (IGFs) have multiple role 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 17 alpha-hydroxylase and type II 3 beta-hydroxysteroid dehydrogenase (3 beta-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 were3 without effect on 11 beta-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.
Kristiansen
S B
SB
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA.
Endoh
A
A
Casson
P R
PR
Buster
J E
JE
Hornsby
P J
PJ
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000302:Adrenal Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000328:Adult; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
D016895:Culture Media, Serum-Free; D007328:Insulin; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I; D000242:Cyclic AMP; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D013254:Steroid 17-alpha-Hydroxylase