Prolactin stimulates transcription of aspartate aminotransferase in prostate cells.
Prolactin (PRL) has been reported to stimulate citrate production and the activity of mitochondrial aspartate aminotransferase (mAAT) and its precursor form pmAAT in prostate epithelial cells. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) caused the same result as PRL, which suggests that the PRL effect on mAAT activity might be mediated by protein kinase C (PKC) stimulation of pmAAT gene transcription. Both PRL and TPA increased the level of pmAAT mRNA by 2.5- to 3-fold in pig prostate cells. The PKC inhibitor gossypol completely inhibited the PRL and TPA induced increases. In addition, the effects of both PRL and TPA were inhibited by down-regulation of prostate PKC. Nuclear run-off assays indicated that PRL and TPA induction of pmAAT occurred primarily at the transcriptional level. The stimulation of pmAAT transcription by TPA suggests that the pmAAT gene contains a TPA response element. Thus, these results are consistent with our previous observation that PRL directly induces pmAAT and that the mechanism of this PRL effect might involve stimulation of PKC.
Franklin
R B
RB
University of Maryland, Dental School, Department of Physiology, Baltimore 21201.
Ekiko
D B
DB
Costello
L C
LC
D000818:Animals; D001219:Aspartate Aminotransferases / Q000096:biosynthesis*; D002478:Cells, Cultured; D002951:Citrates / Q000378:metabolism; D019343:Citric Acid; D004247:DNA / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D004847:Epithelial Cells; D006072:Gossypol / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D002951:Citrates; D019343:Citric Acid; D011388:Prolactin; D004247:DNA; D001219:Aspartate Aminotransferases; D011493:Protein Kinase C; D006072:Gossypol; D013755:Tetradecanoylphorbol Acetate