Expression and regulation of aromatase cytochrome P450 in THP 1 human myeloid leukaemia cells.
Aromatase cytochrome P450 mRNA and activity was strongly expressed in THP 1 myeloid leukaemia cells after treatment with phorbol-myristate-acetate (PMA) and dexamethasone, low level expression was caused by calcitriol. mRNA species of 4.0, 3.0, 2.4 and 1.1 kb size were differentially stimulated. After calcitriol-mediated differentiation (72 h, measured by CD 14 expression) mRNA expression was further enhanced by PMA (45-fold), dexamethasone (15-fold), oestradiol (3.7-fold), testosterone (2.5-fold) and androstenedione (3.5-fold). Forskolin, cAMP and follicle stimulating hormone had no stimulatory effect. Oestradiol formation from testosterone (oestradiol radioimmunoassay in culture supernatants) increased to > 2000 pg/ml/10(6) cells/24 h after PMA-stimulation, mirrored mRNA expression and was suppressed below 10% of original values in the presence of 4-OH-androstenedione. Exons I.2 and I.4 were expressed in PMA-stimulated cells only, exon I.3 in both PMA- and dexamethasone-stimulated cells. A new splicing variant was expressed after calcitriol-stimulation, which did not hybridize to an exon II-derived oligonucleotide but to an exon III-derived one. Local aromatisation of androgens into oestradiol may be important in the concerted crosstalk of cells of the monocyte/macrophage lineage with their respective tissues in inflammation and bone metabolism.
Jakob
F
F
Klinische Forschergruppe 'Zelldifferenzierung und Lokale Regulationssysteme, University of Würzburg, Germany.
Homann
D
D
Seufert
J
J
Schneider
D
D
Köhrle
J
J
D000735:Androstenedione / Q000494:pharmacology; D001141:Aromatase / Q000235:genetics*; D001483:Base Sequence; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000201:enzymology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D013739:Testosterone / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D003907:Dexamethasone; D001141:Aromatase; D012194:RNA-Directed DNA Polymerase; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate