Caspase-3 and -6 expression and activation are targeted by hormone action in the rat ventral prostate during the apoptotic cell death process.

Abstract

Although the apoptotic cell death process in the prostate is known to be under the control of androgens, the key components targeted by the hormones remain to be investigated. In the present study, we report that the expression and the activation of the effector caspases-3 and -6 are under the control of testosterone in the adult rat ventral prostate. By using a model of adult castrated rats supplemented (or not) with androgens, we observed an increase in caspase-3 (3-fold) and -6 (4-fold) mRNA (P < 0.0001) and procaspase-3 (32 kDa) and -6 (34 kDa) protein levels by 3 days and 1 wk, respectively, after castration in the ventral prostate. Castration also induced an increase in the activation of the procaspases in the ventral prostate, since active (cleaved) caspase-3 (17 kDa) and -6 (12 kDa) forms reached maximal levels by 1 wk after castration. Testosterone administration to castrated adult rats prevented the increase in caspase-3 and -6 mRNA as well as in procaspase-3 and -6 and active caspase-3 and -6 levels in the ventral prostate lobe. In contrast, no changes were observed in the initiator caspase-8 mRNA and protein (procaspase and active) levels after castration. No changes in caspase-3 and -6 expression and activation were observed in the dorsolateral and anterior prostate lobes after castration and testosterone supplementation. Together, the present results show that testosterone inhibits apoptosis in the ventral prostate by potentially targeting the transcriptional activity of effector caspase-3 and -6 genes (but not of casapase-8 gene) as well as the cleavage of procaspase-3 and -6 into active enzymes.