Regulation of HSD17B1 and SRD5A1 in lymphocytes.
We previously reported lymphocyte expression of genes encoding enzymes required for steroid metabolism; however, only 17beta-HSD and 5alpha-reductase showed significant enzyme activity. We now investigate regulation of lymphocyte expression for genes encoding 17beta-HSD and 5alpha-reductase. Cultured human T and B lymphoid cell lines and peripheral blood mononuclear cells were treated with known regulators of steroidogenic gene expression including forskolin, PMA, ionomycin, various steroids, interleukin (IL)-4, and IL-6. Treatment with 10 or 50 microM forskolin resulted in a 20-60% reduction of expression for HSD17B1 (encoding 17beta-HSD I) in T and B lymphoid cell lines and peripheral blood mononuclear cells, although such a change was not observed in the expression of SRD5A1 (encoding 5alpha-reductase I). No significant changes were found when cells were treated for 24 h with various concentrations of PMA or ionomycin. Incubation with 10(-9) to 10(-7) M androstenedione or estradiol increased expression of HSD17B1, while testosterone decreased the expression of this gene. SRD5A1 expression was increased in the presence of 5alpha-DHT although no consistent changes were observed when the cells were treated with testosterone. Other steroids, including dexamethasone, progesterone, and 6-hydroxypregnanolone, produced no effects on expression of either HSD17B1 or SRD5A1. Treatment with 0.1-10 ng/ml of IL-4 or IL-6 also did not effect significant changes in gene expression. These data implicate the involvement of the cAMP-protein kinase signal transduction pathway in regulating lymphocyte expression of HSD17B1. Furthermore, it appears that lymphocyte HSD17B1 and SRD5A1 are regulated to some extent by specific steroids.
Zhou
Z
Z
Department of Pediatrics, North Shore University Hospital-NYU School of Medicine, Manhasset, New York, 11030, USA.
Speiser
P W
PW
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D001402:B-Lymphocytes / Q000201:enzymology; D002460:Cell Line; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D019169:Jurkat Cells; D008214:Lymphocytes / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000494:pharmacology; D013601:T-Lymphocytes / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D015850:Interleukin-6; D012333:RNA, Messenger; D013256:Steroids; D005576:Colforsin; D015847:Interleukin-4; D015759:Ionomycin; D015067:17-Hydroxysteroid Dehydrogenases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D013755:Tetradecanoylphorbol Acetate