Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Effects of castration on plasminogen activator activities and plasminogen activator inhibitor type 1 in the rat ventral prostate. 860

Addition of basic fibroblast growth factor (bFGF) to a rat mammary gland myoepithelial cell line (25.5-G4.2.3) resulted in a six- to eightfold increase in cellular and secreted urokinase-type plasminogen activator (uPA) activity after a lag phase of 5-8 h. bFGF had no effect on the uPA activity of mammary epithelial cells. bFGF was active on myoepithelial cells over a narrow concentration range (0.5-2 ng/ml). The bFGF-induced increase in uPA activity was inhibited in a dose-dependent manner by hydrocortisone and transforming growth factor-beta1 (TGF-beta1). Hydrocortisone also inhibited the basal secretion of uPA, as did interleukin-1beta and phorbol myristate acetate, both of which increase uPA levels in other cell systems. The effects of bFGF could also be inhibited by factors which bind bFGF, e.g., heparin and methylamine a2-macroglobulin. TGF-beta1, but not bFGF, induced the synthesis of plasminogen activator inhibitor-1 in the myoepithelial cell line. Mammary gland myoepithelial cells contribute to the synthesis of and are located next to the basement membrane. Myoepithelial-derived uPA is probably associated with basement membrane turnover. The mammary gland basement membrane undergoes many cycles of remodeling and multiple mechanisms may be required to regulate uPA activity.
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PMID:Regulation of urokinase-type plasminogen activator production by rat mammary myoepithelial cells. 889 73