Abstract | CONTEXT:
Endometriosis, the growth of endometrial tissue outside the uterus, is principally an estrogen-dependent disease. In contrast, exposure to progesterone during pregnancy or therapeutically has been shown to provide benefit to some women with this disease. However, recent research suggests that the presence of endometriosis impairs the capacity of the eutopic endometrium to respond to endogenous progesterone. OBJECTIVE: SETTING: This study was performed at a university-based medical center. PARTICIPANTS: Asymptomatic volunteers and patients with endometriosis were studied. MAIN OUTCOME MEASURES: We examined the ability of TNPR to down-regulate endometrial MMP expression in vitro compared with that of natural progesterone and two currently marketed synthetic steroidal progestins. Using a human/mouse model of endometriosis, we also tested the in vivo ability of TNPR to regress ectopic lesions established by tissues with reduced progesterone sensitivity. RESULTS: TNPR effectively down-regulated MMP expression in vitro and induced significant reduction of lesions in mice with disease established by tissues from endometriosis patients. CONCLUSION: Given the positive preclinical pharmacological profile of TNPR that has recently been reported, additional development of this compound for the treatment of endometriosis is warranted.
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Authors | Kaylon L Bruner-Tran, Zhiming Zhang, Esther Eisenberg, Richard C Winneker, Kevin G Osteen |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 91
Issue 4
Pg. 1554-60
(Apr 2006)
ISSN: 0021-972X [Print] United States |
PMID | 16418212
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Benzoxazines
- Receptors, Progesterone
- Thiones
- Matrix Metalloproteinase 3
- Matrix Metalloproteinase 7
- tanaproget
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Topics |
- Adolescent
- Adult
- Benzoxazines
(pharmacology, therapeutic use)
- Blotting, Western
- Cells, Cultured
- Down-Regulation
(drug effects)
- Endometriosis
(drug therapy, pathology)
- Endometrium
(drug effects, metabolism, pathology)
- Female
- Humans
- Matrix Metalloproteinase 3
(biosynthesis, genetics)
- Matrix Metalloproteinase 7
(biosynthesis, genetics)
- Middle Aged
- Organ Culture Techniques
- Receptors, Progesterone
(agonists)
- Stromal Cells
(metabolism)
- Thiones
(pharmacology, therapeutic use)
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