Aberrant
aromatase expression in stromal cells of
endometriosis gives rise to conversion of circulating
androstenedione to
estrone in this tissue, whereas
aromatase expression is absent in the eutopic endometrium. In this study, we initially demonstrated by Northern blotting transcripts of the reductive
17beta-hydroxysteroid dehydrogenase (17betaHSD) type 1, which catalyzes the conversion of
estrone to 17beta-estradiol, in both eutopic endometrium and
endometriosis. Thus, it follows that the product of the
aromatase reaction, namely
estrone, that is weakly estrogenic can be converted to the potent
estrogen, 17beta-estradiol, in endometriotic tissues. It was previously demonstrated that
progesterone stimulates the inactivation of 17beta-estradiol through conversion to
estrone in eutopic endometrial epithelial cells. Subsequently, 17betaHSD type 2 was shown to catalyze this reaction, and its transcripts were detected in the epithelial cell component of the eutopic endometrium in secretory phase. Because 17beta-estradiol plays a critical role in the development and growth of
endometriosis, we studied 17betaHSD-2 expression in endometriotic tissues and eutopic endometrium. We demonstrated, by Northern blotting, 17betaHSD-2 messenger
ribonucleic acid (
RNA) in all
RNA samples of secretory eutopic endometrium (n=12) but not in secretory samples of endometriotic lesions (n=10), including paired samples of endometrium and
endometriosis obtained simultaneously from eight patients. This
messenger RNA was not detectable in any samples of proliferative eutopic endometrium or
endometriosis (n=4) as expected. Next, we confirmed these findings by demonstration of immunoreactive 17betaHSD-2 in epithelial cells of secretory eutopic endometrium in 11 of 13 samples employing a
monoclonal antibody against 17betaHSD-2, whereas 17betaHSD-2 was absent in paired secretory endometriotic tissues (n=4). Proliferative eutopic endometrial (n=8) and endometriotic (n=4) tissues were both negative for immunoreactive 17betaHSD-2, except for barely detectable levels in 1 eutopic endometrial sample. Finally, we sought to determine whether deficient 17betaHSD-2 expression in endometriotic tissues is due to impaired
progesterone action in
endometriosis. We determined by immunohistochemistry the expression of
progesterone and
estrogen receptors in these paired samples of secretory (n=4) and proliferative (n=4) eutopic endometrium and
endometriosis, and no differences could be demonstrated. In conclusion, inactivation of 17beta-estradiol is impaired in endometriotic tissues due to deficient expression of 17betaHSD-2, which is normally expressed in eutopic endometrium in response to
progesterone. The lack of 17betaHSD-2 expression in
endometriosis is not due to alterations in the levels of immunoreactive
progesterone or
estrogen receptors in this tissue and may be related to an inhibitory aberration in the signaling pathway that regulates 17betaHSD-2 expression.