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

Khaled Zeitoun, Kazuto Takayama, Hironobu Sasano, Takashi Suzuki, Nabil Moghrabi, Stefan Andersson, Alan Johns, Li Meng, Michael Putman, Bruce Carr, Serdar E. Bulun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

329 Scopus citations


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 17β-hydroxysteroid dehydrogenase (17βHSD) type 1, which catalyzes the conversion of estrone to 17β-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, 17β-estradiol, in endometriotic tissues. It was previously demonstrated that progesterone stimulates the inactivation of 17β-estradiol through conversion to estrone in eutopic endometrial epithelial cells. Subsequently, 17βHSD 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 17β-estradiol plays a critical role in the development and growth of endometriosis, we studied 17βHSD-2 expression in endometriotic tissues and europic endometrium. We demonstrated, by Northern blotting, 17βHSD-2 messenger ribonucleic acid (RNA) in all RNA samples of secretory entopic 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 europic endometrium or endometriosis (n = 4) as expected. Next, we confirmed these findings by demonstration of immunoreactive 17βHSD-2 in epithelial cells of secretory eutopic endometrium in 11 of 13 samples employing a monoclonal antibody against 17βHSD-2, whereas 17βHSD-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 17βHSD- 2, except for barely detectable levels in I eutopic endometrial sample. Finally, we sought to determine whether deficient 17βHSD-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 17β- estradiol is impaired in endometriotic tissues due to deficient expression of 17βHSD-2, which is normally expressed in eutopic endometrium in response to progesterone. The lack of 17βHSD-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 17βHSD-2 express.

Original languageEnglish (US)
Pages (from-to)4474-4480
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Issue number12
StatePublished - 1998

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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