Protein kinase C alpha, epsilon and AP-1 mediate prolactin regulation of mitochondrial aspartate aminotransferase expression in the rat lateral prostate

Citrate accumulation and secretion are physiological functions of the prost ate gland that are regulated by testosterone and prolactin. The metabolic p athway for citrate production in the prostate involves the activity of mito chondrial aspartate aminotransferase (mAAT). The expression of mAAT in the prostate is regulated by prolactin through a signal transduction pathway me diated by protein kinase C (PKC). In this report we determined which PKC is oforms are expressed in rat lateral prostate epithelial cells and their act ivation by prolactin. Eight PKC isoforms are expressed in the ventral and l ateral prostate lobes. Although all eight isoforms are expressed, only PKC alpha and PKC epsilon were stimulated by prolactin and only in the lateral prostate lobe. Activator protein-1 (AP-1) appears to be the target of prola ctin-PKC signaling because prolactin stimulated nuclear protein binding to an AP-1 consensus oligodeoxynucleotide. Moreover, the nuclear binding prote in stimulated by prolactin also bound an mAAT oligodeoxynucleotide that con tained an AP-1 consensus sequence and which competed for binding with the c onsensus AP-1 oligodeoxynucleotide. A PKC epsilon antisense oligodeoxynucle otide blocked expression of mAAT mRNA. Thus, we conclude that PKC epsilon i s a specific PKC isoform that mediates via AP-1 the signal for prolactin re gulation of mAAT gene expression in rat lateral prostate epithelial cells. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.