Differential effect of keratinocyte growth factor (KGF) on aromatase activity in cultured canine prostatic epithelial cells.

We have recently cloned the mRNA encoding KGF from canine prostate and produced recombinant canine KGF (rcKGF) which specifically acts on cultured canine prostatic epithelial cells (CCPECs) which possess KGF receptors (Canatan et al., 1996; DNA Cell Biol. 15:247). In the present study, the effect of rcKGF on aromatase activity in CCPECs from young (6-month-old) and mature (3-year-old) dogs was examined. Release of (H2O)-H-3 from labeled substrate was used as the indicator of aromatase activity. CCPECs were pulsed with [1-beta-H-3]-androstenedione (1 mu Ci/ml, 6 hr). The amounts of (H2O)-H-3 released into culture medium were measured (dpm) and total cellular proteins were determined. Aromatase activity was expressed as (H2O)-H-3 dpm/mg cellular protein (mean+/-SEM). The basal level of aromatase activity in CCPECs from mature dogs was approximately 4 times higher (p<0.05) than that in cells from young dogs. Aromatase activity in CCPECs from mature dogs increased in a dose-dependent manner upon treatment with rcKGF. Interestingly, rcKGF, at any of the concentrations tested, had no significant effect on aromatase activity in CCPECs from young dogs. These results are the first to indicate that aromatase activity is affected by KGF in mature CCPECs, suggesting that KGF may be involved indirectly in the etiology of benign prostatic hyperplasia by increasing aromatase activity and thus increasing aromatization of androgens. Aromatase induction by KGF may explain at least in part, the increased aromatization of androgens observed in aged dogs. The exact mechanism of how KGF induces aromatase activity in CCPECs is needed to be addressed further.