Deficient 17 beta-hydroxysteroid dehydrogenase type 2 expression in endometriosis: Failure to metabolize 17 beta-estradiol

Aberrant aromatase expression in stromal cells of endometriosis gives rise to conversion of circulating androstenedione to estrone in this tissue, whe reas aromatase expression is absent in the eutopic endometrium. In this stu dy, we initially demonstrated by Northern blotting transcripts of the reduc tive 17 beta-hydroxysteroid dehydrogenase (17 beta HSD) type 1, which catal yzes the conversion of estrone to 17 beta-estradiol, in both eutopic endome trium and endometriosis. Thus, it follows that the product of the aromatase reaction, namely estrone, that is weakly estrogenic can be converted to th e patent estrogen, 17 beta-estradiol, in endometriotic tissues. It was previously demonstrated that progesterone stimulates the inactivatio n of 17 beta-estradiol through conversion to estrone in eutopic endometrial epithelial cells. Subsequently, 17 beta HSD type 2 was shown to catalyze t his reaction, and its transcripts were detected in the epithelial cell comp onent of the eutopic endometrium in secretory phase. Because 17 beta-estrad iol plays a critical role in the development and growth of endometriosis, w e studied 17 beta HSD-2 expression in endometriotic tissues and eutopic end ometrium. We demonstrated, by Northern blotting, 17 beta HSD-2 messenger ri bonucleic acid (RNA) in all RNA samples of secretory eutopic endometrium (n = 12) but not in secretory samples of endometriotic lesions (n = 10), incl uding paired samples of endometrium and endometriosis obtained simultaneous ly from eight patients. This messenger RNA was not detectable in any sample s of proliferative eutopic endometrium or endometriosis (n = 4) as expected . Next, we confirmed these findings by demonstration of immunoreactive 17 b eta HSD-2 in epithelial cells of secretory eutopic endometrium in 11 of 13 samples employing a monoclonal antibody against 17 beta HSD-2, whereas 17 b eta HSD-2 was absent in paired secretory endometriotic tissues (n = 4). Pro liferative eutopic endometrial (n = 8) and endometriotic (n = 4) tissues we re both negative for immunoreactive 17 beta HSD-2, except for barely detect able levels in 1 eutopic endometrial sample. Finally, we sought to determin e whether deficient 17 beta HSD-2 expression in endometriotic tissues is du e to impaired progesterone action in endometriosis. We determined by immuno histochemistry the expression of progesterone and estrogen receptors in the se paired samples of secretory (n = 4) and proliferative (n = 4) eutopic en dometrium and endometriosis, and no differences could be demonstrated. In c onclusion, inactivation of 17 beta-estradiol is impaired in endometriotic t issues due to deficient expression of 17 beta HSD-2, which is normally expr essed in eutopic endometrium in response to progesterone. The lack of 17 be ta HSD-2 expression in endometriosis is not due to alterations in the level s of immunoreactive progesterone or estrogen receptors in this tissue and m ay be related to an inhibitory aberration in the signaling pathway that reg ulates 17 beta HSD-2 expression.