ANDROGEN REGULATION OF RIBOSOMAL-RNA SYNTHESIS IN LNCAP CELLS AND RATPROSTATE

Androgen-dependent growth of prostate tissue has been well documented. An additional prerequisite for cellular growth is the accumulation of ribosomes. It is thus reasonable to hypothesize that ribosomal DNA (r DNA) transcription in prostate tissue must be stimulated by androgen e ither directly or indirectly. This hypothesis was tested using both LN CaP cells, an androgen-dependent tissue culture line and in a rat anim al model. Nuclear run-on assays confirmed that the administration of D HT to LNCaP cells resulted in a two- to three-fold increase in the rat e of rRNA synthesis when compared to cells maintained in the absence o f androgen. Enzymatic analysis and Western blots were carried out to m easure the amount (activity and mass) of RNA polymerase I in DHT treat ed LNCaP cells. These assays demonstrated that neither the catalytic a ctivity of RNA polymerase I nor the amount of the enzyme varied in res ponse to DHT. However, Western blots revealed that the amount of the a uxiliary RNA polymerase I transcription factor UBF, was significantly increased (two- to three-fold) in cells grown in the presence of DHT. Similar experiments were carried out with prostatic tissue obtained fr om orchiectomized rats maintained on either placebo or testosterone pe llets. In this model, both the catalytic activity as well as the amoun t of RNA polymerase I protein decreased. However, in agreement with th e tissue culture model, UBF protein decreased in prostates from orchie ctomized rats and was maintained in animals supplemented with testoste rone. These lines of evidence are consistent with the hypothesis that androgens stimulate rRNA synthesis by increasing the quantities of the components of the rDNA transcription system. Copyright (C) 1996 Elsev ier Science Ltd.