GOSSYPOL INDUCES SPERMIDINE SPERMINE N-1-ACETYLTRANSFERASE IN CANINE PROSTATE EPITHELIAL-CELLS/

Gossypol is an antisteroidogenic compound naturally found in cottonsee d. Gossypol has been shown to inhibit steroidogenesis in the canine pr ostate and may inhibit canine prostate growth. Its mechanism of action , however, is largely unknown. Our laboratory has previously demonstra ted that in vivo administration of gossypol to male dogs can reduce ci rculating levels of testosterone and estradiol. Gossypol also showed a n ability to reduce prostate weights. To search for genes regulated by gossypol in the canine prostate, differential display RT-PCR was perf ormed on total RNAs isolated from control and gossypol-treated male do gs. Grossypol was demonstrated to induce expression of spermidine/sper mine-N-1-acetyltransferase (SSAT), the major catabolic enzyme for poly amines. This induction was confirmed by Northern hybridization analysi s of total RNA isolated from prostates of mature dogs treated with gos sypol for 2 months. Gossypol was also shown to inhibit the progression of cells into the S phase mediated by spermidine. Our findings suppor t the notion that gossypol can inhibit prostate cell proliferation and may be a potential therapeutic agent for use in controlling overgrowt h of the prostate. (C) 1997 Academic Press.