Terazosin modifies the content of glycosaminoglycans and the activity of matrix metalloproteinase 2 in the rat ventral prostate.
OBJECTIVE
We have investigated the effects of terazosin on the content of glycosaminoglycans (GAGs), the activity of matrix metalloproteinase 2 (MMP-2) and MMP-9, and the content of tissue inhibitors of MMP (TIMP) in the ventral prostate of Wistar rats.


METHODS
Rats were treated with terazosin (0.12, 1.2mg/kg orally every second day) for 120 d. GAGs were isolated and purified from ventral prostate homogenates by lipid extraction, ethanol precipitation, and extensive digestion with pronase and DNAse, separated by electrophoresis, and characterised using specific enzymes. The activity of MMP-2 and MMP-9 was estimated using gelatin zymography and TIMP-1 and TIMP-2 were measured by enzyme-linked immunosorbent assay.


RESULTS
Terazosin treatment did not affect the weight of the ventral prostate gland. The prostate contains hyaluronic acid, chondroitin sulfate (CS), dermatan sulfate (DS), and heparan sulfate (HS), MMP-2, TIMP-1, and TIMP-2, but not MMP-9. Terazosin caused a significant increase in the relative content of DS and a significant decrease in the relative content of CS and to a lesser extent of HS. Terazosin evoked a significant increase in the activity of proMMP-2 and MMP-2 but did not affect TIMP.


CONCLUSIONS
The differential effect of terazosin treatment in GAG molecules of the rat prostate may be beneficial because CS is known to induce and DS to inhibit cell proliferation. The effect of terazosin on GAGs and MMP-2 may contribute in the molecular mechanisms of terazosin-induced apoptosis because HS and CS have a proapoptotic effect, whereas DS and MMP-2 are antiapoptotic.
Mitropoulos
Dionisios
D
1st Department of Urology, University of Athens Medical School, Athens, Greece.
Papakonstantinou
Eleni
E
Aletras
Alexios J
AJ
Kalinderis
Nikolaos
N
Zervas
Anastasios
A
Hatzichristou
Dimitrios
D
Karakiulakis
George
G
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D006025:Glycosaminoglycans / Q000032:analysis*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects* / Q000378:metabolism*; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011467:Prostate / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000317:Adrenergic alpha-Antagonists; D006025:Glycosaminoglycans; C041226:Terazosin; D020778:Matrix Metalloproteinase 2; D011224:Prazosin