Effects of castration on plasminogen activator activities and plasminogen activator inhibitor type 1 in the rat ventral prostate.
The involution of the prostate gland after castration is an active process which requires the induction of new proteins. The plasminogen activator urokinase has been proposed to be a gene repressed by androgen which is activated upon castration and thus participating in the atrophy of the gland. However, urokinase is secreted by the ventral lobe of the rat prostate and this should be positively affected by androgens. The purpose of this study was to examine further the effects of castration upon plasminogen activator (PA) activities in the rat prostate and to determine possible explanations to this apparent dilemma. Castration of young sexually mature adult rats resulted in a substantial increase in PA activities at 4 days after castration in the ventral prostate, but then the activities returned to within the range of untreated animals with a longer duration of castration. Urokinase was the predominant molecular form of PA in the normal ventral prostate and it was the molecular form increased after castration; based upon its sensitivity to amiloride and its molecular size determined in zymograms. In contrast to the effect of castration, there was no increase in PA activities in the ventral prostate with treatment of rats with the antiandrogen flutamide, but rather a decrease when specific activity was expressed per unit DNA. In addition, the effect of castration was specific for the ventral lobe for there was no change in the PA activity in the dorsolateral prostate after androgen ablation. The diminished PA activities in the ventral prostates of rats castrated for 7 days or longer appeared to be due at least in part to an increase in plasminogen activator inhibitor type-1 (PAI-1). Immunoreactive PAI-1 was found predominantly in high molecular weight forms which indicates that the inhibitor was complexed with PA. Daily treatment of rats upon castration with agents known to retard the rate of regression of the involuting prostate gave dichotomous results. Hydrocortisone prevented the increase in PA activity, whereas treatment with actinomycin D, an inhibitor of RNA synthesis, not only did not prevent an increase in PA activity, but actually produced a superinduction in PA activity at 4 days orchiectomy. These data may be interpreted to mean that hydrocortisone stimulated PAI activity and that actinomycin D treatment blocked its induction. However, the actinomycin D data may also indicate that an increase in urokinase protein and mRNA after castration may result from some mechanism to conserve these molecules suggesting that this inhibitor of RNA synthesis prevented the transcription of messages for proteins involved in the degradation of urokinase message.
Wilson
M J
MJ
VA Medical Center, Minneapolis, MN 55417, USA.
Ludowese
C
C
Sinha
A A
AA
Estensen
R D
RD
D000584:Amiloride / Q000494:pharmacology; D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005485:Flutamide / Q000494:pharmacology; D005786:Gene Expression Regulation; D006854:Hydrocortisone / Q000494:pharmacology; D015151:Immunoblotting; D008297:Male; D009919:Orchiectomy; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D010960:Plasminogen Activators / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D011467:Prostate / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology; D014148:Tranexamic Acid / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology
D000726:Androgen Antagonists; D000893:Anti-Inflammatory Agents; D004232:Diuretics; D017395:Plasminogen Activator Inhibitor 1; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D013739:Testosterone; D014148:Tranexamic Acid; D005485:Flutamide; D000584:Amiloride; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D006854:Hydrocortisone