Effect of estrogen therapy on vascular perlecan and metalloproteinases 2 and 9 in castrated rats.
OBJECTIVE
To study the effects of estrogen therapy on the expression of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) and perlecan in the vascular wall.


METHODS
Twenty 180-day-old Wistar rats were castrated and treated 1 week later for a period of 4 weeks with one of the following: (1) placebo; (2) 0.5 μg/day estradiol benzoate (E(2)B); (3) 5 μg/day E(2)B; (4) 50 μg/day E(2)B. A fifth group consisted of rats that had not been castrated. Following treatment, expression of MMP-2 and MMP-9 mRNA (MMP-2([RNA]) and MMP-9([RNA]), respectively) was analyzed by real-time PCR, and expression of MMP-2 (MMP-2([IH])), MMP-9 (MMP-9([IH])) and perlecan was quantified by immunohistochemistry, in carotid walls.


RESULTS
There were no differences among castrated groups for MMP-2([RNA]) (p = 0.1969) and for MMP-9([RNA]) (p = 0.1828); however, a correlation was observed between E(2)B dose and MMP-9([RNA]) levels (r = 0.471, p = 0.018). Differences among groups were observed for MMP-2([IH]), MMP-9([IH]) and perlecan (p < 0.0001), wherein higher levels were observed in animals treated with estrogen therapy, correlating with E(2)B doses in the case of MMP-9 (r = 0.441, p = 0.026) and perlecan (r = 0.574, p = 0.005).


CONCLUSIONS
Estrogen therapy correlates with higher levels of MMP-2, MMP-9 and perlecan in the extracellular matrix of carotid walls in castrated rats, in a dose-dependent manner. There was a dose-response effect of E(2)B on the expression of MMP-9 mRNA and, possibly, MMP-2 mRNA.
Department of Gynecology and Obstetrics, Faculdade de Medicina do ABC, Santo André, Brazil.
L M
LM
Pompei
M L
ML
Steiner
T R
TR
Theodoro
P Z
PZ
Souza
A C A
AC
Romanini
V
V
Coulson-Thomas
M A S
MA
Pinhal
C E
CE
Fernandes
D000704:Analysis of Variance; D000818:Animals; D002339:Carotid Arteries / Q000201:enzymology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
D004967:Estrogens; D019812:Heparan Sulfate Proteoglycans; D012333:RNA, Messenger; C071927:perlecan; C074283:estradiol 3-benzoate; D004958:Estradiol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9