LOW EXPRESSION OF 3-BETA-HYDROXY-5-ENE STEROID DEHYDROGENASE GENE IN HUMAN FETAL ADRENALS INVIVO - ADRENOCORTICOTROPIN AND PROTEIN-KINASE C-DEPENDENT REGULATION IN ADRENOCORTICAL CULTURES

Human fetal adrenals are very active in steroid production. They make large amounts of dehydroepiandrosterone sulfate which is further converted to estrogens in placenta. Fetal adrenals cannot make cortisol efficiently from cholesterol or pregnenolone, but they can convert progesterone to cortisol. To clarify the molecular basis of the very low activity of 3-beta-hydroxy-5-ene steroid dehydrogenase (3-beta-HSD) in human fetal adrenals we studied the expression of 3-beta-HSD gene in fetal adrenals in vivo and in culture conditions. Human adult adrenals, placenta and a testicular Leydig cell tumor clearly expressed 3-beta-HSD gene when studied by Northern blotting, but fetal adrenals and ovaries had no detectable 3-beta-HSD mRNA by this method. Polymerase chain reaction analysis of cDNA samples derived from different human tissues revealed 3-beta-HSD gene expression in placenta, adult adrenal and adult ovarian granulosa cells after 25 cycles of amplification. Fetal adrenal samples became positive only after additional amplification cycles, which verifies the very low expression of 3-beta-HSD gene in fetal adrenals. In cell culture conditions both ACTH and a protein kinase C regulator 12-O-tetradecanoyl phorbol-13-acetate induced 3-beta-HSD gene expression. We conclude: 1) the very low activity of 3-beta-HSD in human fetal adrenals is due to the low expression of this gene; 2) both cAMP and protein kinase C-dependent mechanisms regulate 3-beta-HSD gene expression in adrenocortical cells.