Is the dose to inhibit the COX-2 enzyme in nude mice also adequate in ‘human’ endometrial tissues?

Sachiko Matsuzaki and Michel Canis

Department of Gynecology, Hôtel-Dieu,Polyclinique, CHU, Clermont-Ferrand, b.p. 69, 13 bd, L. Mafreyt, 63058, Clermont-Ferrand, France

Email: smatsuzaki{at}chu-clermontferrand.fr

Sir,

We read with great interest the paper by Hull et al. (2005)Go. The authors examined whether nimesulide, a COX-2 inhibitor, reduced the size and number of ectopic human endometrial lesions in a nude mouse model of endometriosis. The authors commented that the dose of nimesulide administered to the nude mice was adequate to inhibit the COX-2 enzyme in vivo.

However, we would like to question whether the dose administered to the nude mice was adequate to inhibit the COX-2 enzyme in ‘human’ endometrial tissues. The authors collected endometrial tissues from patients with endometriosis during the secretory phase and injected them into nude mice. Endometrial tissues from patients with endometriosis have higher levels of COX-2 protein than those of women without endometriosis during the secretory phase (Ota et al., 2001Go; Matsuzaki et al., 2004aGo). The authors detected positive COX-2 staining in ectopic human endometrial cells after treatment, whereas minimal COX-2 staining was detected in mouse uterine tissues. Although protein expression levels do not reflect COX-2 enzymatic activity, these results suggest that the dose of nimesulide was not adequate to inhibit the COX-2 enzyme in human endometrial tissues, whereas it was adequate in mouse uterine tissues. Surprisingly, the authors did not provide any results of COX-2 protein expression levels in ectopic endometrial tissues between COX-2 inhibitor-treated mice and controls, and those in the secretory human endometrial tissues before injection.

We recently reported that celecoxib, a COX-2-selective inhibitor treatment, significantly reduced size and number of implants (autotransplantated uterine tissues) in a rat model of endometriosis. Experimental approaches such as that taken in our study lack the power to determine whether observed effects result specifically from inhibition of COX-2 expression. Thus, we further analysed COX-2 expression in ectopic implants using an immunohistochemical technique. Expression of COX-2 in ectopic implants in treated rats was markedly reduced compared with that seen in controls (Matsuzaki et al., 2004bGo). The authors concluded that the COX-2 inhibitor nimesulide did not reduce lesion size or number in the nude mice model of endometriosis. However, before drawing any conclusions, it is obviously necessary to measure COX-2 enzymatic activity in ectopic human endometrial tissues both in COX-2 inhibitor-treated mice and controls in order to confirm that the dose administered to the nude mice was adequate to inhibit the COX-2 enzyme in human endometrial tissues.

References

Hull ML, Prentice A, Wang DY, Butt RP, Phillips SC, Smith SK and Charnock-Jones DS (2005) Nimesulide, a COX-2 inhibitor, does not reduce lesion size or number in a nude mouse model of endometriosis. Hum Reprod 20, 350–358.[Abstract/Free Full Text]

Matsuzaki S, Canis M, Pouly JL, Wattiez A, Okamura K and Mage G (2004a) Cyclooxygenase-2 expression in deep endometriosis and matched eutopic endometrium. Fertil Steril 82, 1309–1315.[CrossRef][ISI][Medline]

Matsuzaki S, Canis M, Darcha C, Dallel R, Okamura K and Mage G (2004b) Cyclooxygenase-2 selective inhibitor prevents implantation of eutopic endometrium to ectopic sites in rats. Fertil Steril 82, 1609–1615.[CrossRef][ISI][Medline]

Ota H, Igarashi S, Sasaki M and Tanaka T (2001) Distribution of cyclooxygenase-2 in eutopic and ectopic endometrium in endometriosis and adenomyosis. Hum Reprod 16, 561–566.[Abstract/Free Full Text]

Submitted on March 9, 2005; accepted on May 5, 2005.





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