Effects Of Letrozole On The Expression Of Aromatase Cytochrome P450and Cyclooxygenase-2in Rat Models Of Endometriosis

Objective To establish rat models of endometriosis, treated them with Letrozole.To analyze the effection of letrozole on endometriosis, and its pathogenesy.Methodsl.40healthy non-pregnant Sprague Dawley (SD) female rats were treated in accordance. The ones which exhibited two consecutive regular estrous cycles were choosed to establish models of endometriosis surgically by using autologous transplantation of endometrium in estruation.2. After four weeks of implantation, the second laparotomy was performed to observe the shape of ectopic implants in estrus.The successful rat models of endometriosis were divided randomly into two groups.The one was the treatment group (n=15) which was given letrozole (0.26mg/kg/d) by oral gavage. The other was the control group (n=15)which was given the same doses of saline, instead of letrozole.Measured the size of the ectopic implants.3. After three weeks’letrozole treatment, the third laparotomy was performed in estrus. Compared the volumes and the histopathology of ectopic implants in each group, Detected the expression of P450arom and COX-2in the tissues by Immunohistochemistry and RT-PCR.Results1. The rate of establishing successful rat models of endometriosis achieved75%.2. The pretreatment volumes of ectopic implants in two groups was siminal to each other (P>0.05). After treatment, the volumes of ectopic implants in treatment group was markedly reduced (P<0.05).While there has no significant changes in control group (P>0.05).3. After letrozole treatment, the glandular epithelium of ectopic endometrium atrophied, the number of glands reduced significantly, interstitial cells arranged in loose and the vascular reduced in the treatment group compared with the control group.4. After letrozole treatment, the levels of protein or mRNA of P450arom and COX-2in treatmet group were both significantly lower in eutopic endometrium than the levels in control group, detected by Immunohistochemistry and RT-PCR respectively(P<0.05). The Pearson correlation analysis that P450arom is positively correlated to COX-2in protein or mRNA in endometriosis progression.Conclusionl. P450arom and COX-2are positively correlated, promoting the development of endometriosis together.2. Letrozole can inhibit the expression of P450arom, control the secretion of estrogen, and decrease the expression of COX-2, reducing the size of ectopic implants directly. It supports that letrozole may act as an efficacious therapy for endometriosis.