The pyruvate dehydrogenase E1 alpha gene is testosterone and prolactin regulated in prostate epithelial cells

The prostate gland of humans and other animals has the unique function of a ccumulating and secreting extraordinarily high levels of citrate. The prost ate secretory epithelial cells synthesize citrate which, due to a limiting mitochondrial (m) aconitase, accumulates rather than being oxidized. Thus c itrate is essentially an end product of metabolism in prostate. For continu ed net citrate production, a continual source of oxaloacetate (OAA) and ace tyl CoA is required. Glucose via pyruvate oxidation provides the source of Acetyl CoA. In prostate cells, citrate production is regulated by testoster one and/or by prolactin. Both hormones selectively regulate the level and a ctivity of pyruvate dehydrogenase E1alpha (E1a) in animal prostate cells th ereby regulating the availability of acetyl CoA for citrate synthesis. Stud ies were conducted to determine if testosterone and prolactin might regulat e the expression of the E1a gene in prostate epithelial cells. Prolactin tr eatment of rat ventral and lateral prostate cells and human PC3 cells incre ased the levels of E1a mRNA and the rates of transcription of the E1a gene. Testosterone also increased the mRNA level and transcription of E1a in rat ventral prostate cells, and in PC3 cells transfected with androgen recepto r. However, testosterone treatment resulted in a repression of E1a gene exp ression in lateral prostate cells. Evidence is presented which supports the view that prolactin regulation of E1a is mediated via PKC. The rapidity of the effects of both hormones is representative of an immediate-early gene response. To our knowledge this represents the first report in any mammalia n cells that, in addition to its constitutive expression in all mammalian c ells, the E1a gene is a hormonally-regulated gene in specifically targeted prostate epithelial cells.