Androgenic effects on protein kinases and cyclic AMP-binding protein in the ventral prostate.

Androgenic deprivation resulted in marked impairment of prostate weight and significant alterations in cytosolic and particulate protein kinase activities and cyclic AMP-binding capacity of this tissue. Whereas rats orchidectomized for 7 days exhibited significant enhancement in the specific activity of cytosolic cyclic AMP-dependent (73%) and -independent (45%) protein kinases as well as cyclic AMP-binding protein (196%), administration of testosterone (5.0 mg/100 g, i.m., 5 days) exerted little or no effect in reversing these responses. In contrast, when expressed as total enzyme activity per prostate, castration led to marked decreases in protein kinase activity assayed in the presence (87%) and absence of the cyclic nucleotide (91%). Likewise, the cyclic AMP-binding capacity of the soluble enzyme was depressed (77%) following androgenic deprivation. Although testosterone treatment for 3 days significantly reversed these effects, complete restoration was not achieved even after 5 days of androgen replacement therapy. Moreover, while exogenous cyclic AMP had no effect on protein kinase activity from crude nuclear preparations, the phosphorylation of endogenous nuclear substrates was dependent on androgenic status of the animals. Whereas castration produced decreases in the specific and total activity of prostatic particulate protein kinase as well as the cyclic AMP-binding protein, testosterone replenishment was effective in abolishing these alterations seen in orchidectomized rats. Data from the present study provide additional support to the concept that changes in cyclic AMP-adenylate cyclase-protein kinase system play an important role in the overall mechanism(s) by which male sex steroids exert their diverse anabolic effects on male accessory sex tissues.