title: Urokinase- and tissue-type plasminogen activators are suppressed by cortisol in the involuting prostate of castrated rats.
abstract: The effects of cortisol on the inhibition of cell-death processes and suppression of plasminogen-activator (PA) activity during involution of the rat ventral prostate gland were investigated to determine the principal type of PA activated by castration and inhibited by this hormone and whether the mechanism responsible for decreased PA activity involved reductions in enzyme synthesis or increased activity of a PA inhibitor. By using the technique of fibrin-agarose zymography, three bands of PA activity were detected at 4 and 7 days after castration: a major band with a molecular mass of approx. 30 kDa and two minor bands of 48 kDa and 64 kDa. Both the 30 kDa and 48 kDa activities were inhibited with anti-[urokinase-type PA (u-PA)] IgG. The 64 kDa activity was inhibited by anti-[tissue-type PA (t-PA)] IgG. In addition to retarding prostatic involution, daily administration of cortisol to the castrated animals suppressed all three bands of PA activity. A comparison of the pattern of total PA activity and of e.l.i.s.a. estimates of u-PA concentration during the castration-induced rise and after cortisol inhibition indicated a near perfect correlation between the two parameters. Northern-blot analysis using prostatic polyadenylated RNA revealed that the level of u-PA mRNA was highest at 4 and 7 days after castration and that cortisol treatment repressed u-PA mRNA to a level similar to that in non-castrated controls. Neither Northern hybridizations nor reverse zymography detected RNA transcripts or activity corresponding to the PA inhibitor PAI-1 in any of the prostate samples. Western-blot analysis revealed that, although the amount of arginine esterase A, another prostatic proteinase, also increased after castration, the rise in concentration of this protein was not blocked by glucocorticoid administration. Together our findings indicate the following: (1) the predominant form of PA activity induced in the prostate after castration and inhibited by cortisol is a 30 kDa form of u-PA. Although less prominent, t-PA and a 48 kDa form of u-PA follow a similar pattern of induction and inhibition; (2) changes in u-PA activity in response to castration and cortisol treatment are due to alterations in the level of u-PA mRNA and protein rather than in the activity of PAI-1; (3) not all castration-induced proteinases in the prostate are inhibited by cortisol.
authors.affiliation: Department of Cancer Endocrinology, Cancer Control Agency of British Columbia, Vancouver, Canada.
authors.forename: S N
authors.initials: SN
authors.lastname: Freeman
authors.forename: P S
authors.initials: PS
authors.lastname: Rennie
authors.forename: J
authors.initials: J
authors.lastname: Chao
authors.forename: L R
authors.initials: LR
authors.lastname: Lund
authors.forename: P A
authors.initials: PA
authors.lastname: Andreasen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006854:Hydrocortisone / Q000494:pharmacology*; D008297:Male; D008970:Molecular Weight; D009693:Nucleic Acid Hybridization; D009919:Orchiectomy; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C019724:arginine esterase; D002265:Carboxylic Ester Hydrolases; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D006854:Hydrocortisone