Role of aromatase in endometrial disease

Bulun, Serdar E.; Yang, Shiyong; Fang, Zongjuan; Gürateş, Bilgin; Tamura, Mitsutoshi; Zhou, Jianfeng; Sebastian, Siby

doi:10.1016/s0960-0760(01)00134-0

Cited by 124 publications

(81 citation statements)

References 27 publications

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“…Since we found no differences in the expression of VEGF-A or its receptors (data not shown), or in the content of VEGF-A in peritoneal fluid or serum, between the proliferative and secretory menstrual phases, other reasons for this may need to be sought. Possible explanatory mechanisms include the ectopic site of growth, the presence of endogenous aromatase activity in the endometriotic lesions (Bulun et al 2001) and the continuous exposure to peritoneal fluid with its content of pro-inflammatory and pro-angiogenic substances, factors that might override or bias the control of proliferation and function that is normally exerted by the ovarian sex steroid hormones. In a previous study, no difference was found in the microvessel density of endometriotic lesions between the different phases of the menstrual cycle (Matsuzaki et al 1998).…”

Section: Angiogenic Activity In Endometriotic Lesionsmentioning

confidence: 99%

The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions

Bourlev¹,

Volkov²,

Pavlovitch

et al. 2006

Reproduction

162

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Studies were performed to elucidate the possible relationship between microvessel density, proliferative activity and angiogenesis in eutopic endometrium from women with and without endometriosis and peritoneal endometriotic lesions. The question whether changes in these parameters in endometriotic lesions were reflected by the level of vascular endothelial growth factor-A (VEGF-A) in serum and peritoneal fluid was also studied. Biopsy specimens of both eutopic endometrium and peritoneal endometriotic lesions from women with endometriosis (nZ25) as well as eutopic endometrium from women without endometriosis (nZ14) were analysed immunohistochemically regarding microvessel density, proliferative activity, and expression of VEGF-A and its receptors vascular endothelial growth factor receptors 1 and 2 (VEGFR-1 and VEGFR-2) in stroma, glands and blood vessels. The VEGF-A concentration was measured in peritoneal fluid and serum. Secretory phase eutopic endometrium from women with endometriosis had significantly higher microvessel density, expression of VEGF-A in glandular epithelium and VEGFR-2 in endometrial blood vessels than those from women without endometriosis. Endometriotic lesions with high proliferative activity had a higher microvessel density and showed higher vascular expression of VEGFR-2 as well as being accompanied by higher levels of VEGF-A in peritoneal fluid and serum, compared with lesions with low proliferative activity. In conclusion, there seems to be a dysregulation of angiogenic activity in the eutopic endometrium of women with endometriosis and endometriotic lesions with high proliferative activity were accompanied by higher local angiogenic activity and higher levels of VEGF in serum and peritoneal fluid.

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Section: Angiogenic Activity In Endometriotic Lesionsmentioning

confidence: 99%

The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions

Bourlev¹,

Volkov²,

Pavlovitch

et al. 2006

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162

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“…With the exception of patient 23, all aromatase-negative lowgrade endometrial stromal sarcomas corresponded to stage I disease (pts. [10][11][12]. Of the five patients with recurrent disease (pts.…”

Section: Resultsmentioning

confidence: 99%

Aromatase expression in low-grade endometrial stromal sarcomas: an immunohistochemical study

Reich

Regauer

2003

Mod Pathol

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Aromatase expression has been described in stromal cells of endometriosis, adenomyosis and endometrial cancer. We analyzed aromatase expression in a series of 23 low-grade endometrial stromal sarcomas. Archival formalin-fixed and paraffin-embedded material was analyzed with immunohistochemistry. Aromatase expression was evaluated with a monoclonal and a polyclonal antibody using the peroxidase-antiperoxidase method. A score was calculated based on the percentage of positive tumor cells and the staining intensity. Aromatase was seen in 19 (83%) of 23 tumors with monoclonal antibody and 20 (87%) of 23 tumors with polyclonal antibody. Aromatase expression using the monoclonal antibody was scored as high in five (22%), moderate in nine (39%) and low in five (22%) tumors. Four (17%) low-grade endometrial stromal sarcomas did not stain for aromatase. Aromatase expression with the polyclonal antibody was scored as high in seven (31%), moderate in four (17%) and low in nine (39%) tumors. Three (13%) low-grade endometrial stromal sarcomas did not stain for aromatase. Little or no aromatase expression tended to correlate with stage I disease, while higher scores were more frequently associated with advanced disease. Our results demonstrate that most low-grade endometrial stromal sarcomas express aromatase. The staining pattern, however, is heterogeneous. The high percentage of aromatase positivity in low-grade endometrial stromal sarcomas may have implications in the management of these tumors and offer new treatment modalities such as hormonal therapy with aromatase inhibitors.

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“…In premenopausal women the ovaries are the primary source of E2, but E2 can also be produced in peripheral tissue from inactive precursors (Labrie et al, 2000). Locally, in endometriotic tissue, E2 can be synthesised in two ways: by the aromatase pathway, which includes conversion of ovarian or adrenal androstenedione to the weakly estrogenic estron (E1); this is further converted to active E2 (Bulun et al, 1999, Bulun et al, 2001) by 17β-hydroxysteroid dehydrogenases (17β-HDSs) types 1, 7 and 12. The reverse reaction is catalyzed by the oxidative 17β-HSDs types 2, 4 and 8 (Luu-The 2001, Penning 2003, Midnich et al, 2004, Vikho et al, 2004, LuuThe et al, 2006.…”

Section: Introductionmentioning

confidence: 99%

“…The reverse reaction is catalyzed by the oxidative 17β-HSDs types 2, 4 and 8 (Luu-The 2001, Penning 2003, Midnich et al, 2004, Vikho et al, 2004, LuuThe et al, 2006. The use of aromatase inhibitors for the treatment of endometriosis has been successful, as this is the rate-limiting step in local E2 production (Bulun et al, 2001, Patwardhan et al, 2008. The other pathway, the so called sulfatase pathway, includes sulfatase and sulfotransferase.…”

Section: Introductionmentioning

confidence: 99%

Disturbed estrogen and progesterone action in ovarian endometriosis

Šmuc

Hevir

Ribič-Pucelj

et al. 2009

Molecular and Cellular Endocrinology

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Please cite this article as:Šmuc, T., Hevir, N., Ribič-Pucelj, M., Husen, B., Thole, H., Rižner, T.L., Disturbed estrogen and progesterone action in ovarian endometriosis, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. SummaryEndometriosis is a very common disease in pre-menopausal women, where defective metabolism of steroid hormones plays an important role in its development and promotion. In the present study, we have examined the expression of 11 estrogen and progesterone metabolizing enzymes and their corresponding receptors in samples of ovarian endometriomas and control endometrium. Expression analysis revealed significant up-regulation of enzymes involved in estradiol formation (aromatase, sulfatase and all reductive 17β-hydroxysteroid dehydrogenases) and in progesterone inactivation (AKR1C1 and AKR1C3). Among the estrogen and progesterone receptors, ERα was down-regulated, ERβ was up-regulated, and there was no significant difference in expression of progesterone receptors A and B (PRAB). Our data indicate that several enzymes of estrogen and progesterone metabolism are aberrantly expressed in endometriosis, which can lead to increased local levels of mitogenic estradiol and decreased levels of protective progesterone. Changes in estrogen receptor expression suggest that estradiol may also act via non-estrogen-receptor-mediated pathways, while expression of progesterone receptors still needs further investigation.

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Role of aromatase in endometrial disease

Cited by 124 publications

References 27 publications

The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions

The relationship between microvessel density, proliferative activity and expression of vascular endothelial growth factor-A and its receptors in eutopic endometrium and endometriotic lesions

Aromatase expression in low-grade endometrial stromal sarcomas: an immunohistochemical study

Disturbed estrogen and progesterone action in ovarian endometriosis

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