Testosterone regulates mitochondrial aspartate aminotransferase gene expression and mRNA stability in prostate.
The effect of testosterone on the precursor mitochondrial aspartate aminotransferase (pmAAT) gene and on pmAAT-mRNA was studied in rat ventral prostate (VP) and pig prostate epithelial cells. Castration significantly decreased the level of nuclear pmAAT transcripts in VP; whereas testosterone treatment of castrated animals restored the level of pmAAT transcripts. Correspondingly, castration resulted in a marked decrease in the transcription rate of the pmAAT gene; whereas testosterone treatment markedly increased the transcription rate. In vitro studies with isolated pig prostate epithelial cells demonstrated that testosterone directly and rapidly induced a transient increase in the transcription rate of the pmAAT gene. The increase in transcription was associated with an increase in the steady-state level of pmAAT-mRNA. Similar in vitro effects were observed with isolated VP epithelial cells. In addition to its stimulatory effect on transcription of the pmAAT gene, testosterone also increased the half-life of pmAAT-mRNA from 2 h in the absence of hormone to 16 h in its presence. Consequently, testosterone appears to stabilize the pmAAT-mRNA. The combination of its immediate effect on stimulating the transcription of the pmAAT gene and its stabilizing effect on pmAAT-mRNA would account for the increase in the steady-state level of pmAAT-mRNA by testosterone. These studies support our proposal that, through these effects, testosterone increases the biosynthesis of mAAT thereby increasing the transamination of aspartate to oxaloacetate and ultimately increasing the synthesis of citrate. This appears to provide at least one of the mechanisms by which testosterone regulates prostate citrate production.
Qian
K
K
University of Maryland Dental School, Department of Physiology, Baltimore 21201.
Franklin
R B
RB
Costello
L C
LC
D000818:Animals; D001219:Aspartate Aminotransferases / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D009919:Orchiectomy; D011467:Prostate / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D013739:Testosterone / Q000502:physiology*
D012333:RNA, Messenger; D013739:Testosterone; D001219:Aspartate Aminotransferases