Low expression of 3 beta-hydroxy-5-ene steroid dehydrogenase gene in human fetal adrenals in vivo; 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.
Voutilainen
R
R
Department of Pediatrics, University of Helsinki, Finland.
Ilvesmäki
V
V
Miettinen
P J
PJ
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000302:Adrenal Cortex / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D002478:Cells, Cultured; D005333:Fetus / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D012333:RNA, Messenger; D013256:Steroids; D000324:Adrenocorticotropic Hormone; D015096:3-Hydroxysteroid Dehydrogenases; C031954:delta(5)-3 beta-hydroxysteroid dehydrogenase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate