EXPRESSION OF G1 CYCLINS, CYCLIN-DEPENDENT KINASES, AND CYCLIN-DEPENDENT KINASE INHIBITORS IN ANDROGEN-INDUCED PROSTATE PROLIFERATION IN CASTRATED RATS

Androgen induces prostate cell proliferation in the castrated rat, We hypothesized that G1 cyclins, cyclin-dependent kinases (cdk), and cdk inhibitors mediate this cellular response to mitogenic signals. In thi s study, induction of cyclins D1, D2, D3, E, and cdks 2, 4, and 6 expr ession was observed at various time points during testosterone replace ment in the ventral prostate of castrated rats. The induction followed prostate epithelium proliferation, which peaked at 48 h and decreased at 120 h during the treatment. The study of cyclin/cdk complex format ion revealed that more cyclin D1/cdk4 and cyclin D1/cdkG complexes wer e formed at 48 h than at 120 h of treatment, but cyclin D1/cdk2 comple xes remained the same. Furthermore, both hyperphosphorylated and hypop hosphorylated forms of Rb were detected at 48 h, but only the hypophos phorylated form was detected at 120 h of treatment, p21(Cip1), which w as very abundant in the ventral prostate of castrated and intact rats, was not detected when the prostate started proliferation and increase d gradually as proliferation decreased during the androgen treatment. Meanwhile, p27(Kip1) dramatically increased after androgen treatment, and the induction levels were less at the peak of prostate proliferati on and higher when proliferation was low. The results presented here s uggest that expression of G1 cyclins and their related kinases and kin ase inhibitors are well regulated after androgen replacement in the ve ntral prostate of castrated rats. The cooperation between these cell c ycle regulators leads to a well-controlled prostate regeneration.