The relationship between inhibition of plasminogen-activator activity and prostatic involution.
The role of plasminogen activators (PAs) as potential mediators of involution of the rat ventral prostate was investigated by using an approach involving the administration in vivo of anti-PA drugs. The prostates of castrated rats, which had been injected daily for 7 days with the anti-PA drugs 6-aminohexanoic acid, tranexamic acid, aprotinin and cortisol, were assayed for PA activity, weight and cell number. In the prostates from the castrated controls, there was a 10-fold increase in the mean PA activity and a 7-fold decrease in cell number relative to that of the non-castrated animals. Although this rise in enzyme activity could be decreased to some extent by all the drugs except aprotinin, only treatment with high doses of tranexamic acid or cortisol had a statistically significant effect. A similar pattern was observed with respect to the relative potency of the drugs in preventing the loss of prostatic weight and cell number after castration. The effects of cortisol were dose-dependent, with complete inhibition of both the rise in PA activity and cell loss occurring at a dose of about 15 mg/day. Since the concentration of the principal intranuclear androgen, dihydrotestosterone, was the same in the prostates from treated and untreated castrated rats, the effects of cortisol are not due to increased retention of this androgen. Rather, the high inverse correlation (r = 0.86) between the cellular concentration of PA activity and the cell population of the prostate implies that PAs are directly associated with prostatic involution and that cortisol, and to a lesser extent tranexamic acid, blocks the involution process through inhibition of PAs.
Rennie
P S
PS
Department of Cancer Endocrinology, Cancer Control Agency of British Columbia, Vancouver, Canada.
Bowden
J F
JF
Bruchovsky
N
N
Cheng
H
H
D000614:Aminocaproates / Q000494:pharmacology*; D015119:Aminocaproic Acid / Q000494:pharmacology*; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011469:Prostatic Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D014148:Tranexamic Acid / Q000494:pharmacology*
D000614:Aminocaproates; D003509:Cyclohexanecarboxylic Acids; D015849:Plasminogen Inactivators; D014148:Tranexamic Acid; D007611:Aprotinin; D010960:Plasminogen Activators; D015119:Aminocaproic Acid; D006854:Hydrocortisone