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*Endometriosis

Journal of Clinical Endocrinology & Metabolism, Vol 81, 174-179, Copyright © 1996 by Endocrine Society

ARTICLES

Aromatase expression in endometriosis

LS Noble, ER Simpson, A Johns and SE Bulun
Cecil H, and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas 75235, USA.

The conversion of C19 steroids to estrogens occurs in a number of tissues, such as the ovary and placenta, and is catalyzed by aromatase P450 (P450arom; the product of the CYP19 gene). P450arom expression has also been detected in a number of uterine tumors, such as leiomyomas and endometrial cancer. On the other hand, P450arom expression was undetectable in normal endometrial and myometrial tissues. The present study was conducted to determine the presence or absence of aromatase expression in peritoneal endometriotic implants and in the eutopic endometrium of women with endometriosis. Endometriotic implants in pelvic peritoneum (n = 17; e.g. posterior culdesac, bladder, and anterior culdesac) and eutopic endometrial curettings (n = 11) of 14 patients with histologically documented pelvic endometriosis were obtained at the time of laparoscopy or laparotomy. Pelvic peritoneal biopsies distal to endometriotic implants as well as normal endometrial tissues (n = 7) from disease-free women were used as negative controls. We used competitive RT-PCR technology employing an internal standard to amplify P450arom transcripts in total ribonucleic acid (RNA) isolated from these tissues. P450arom transcripts were detected in all endometriotic implants and in all eutopic endometrial tissues from patients with endometriosis. P450arom messenger RNA species were not detectable in endometrial tissues from disease-free women or in endometriosis-free peritoneal tissues. The highest levels of transcripts were detected in an endometriotic implant that involved the full thickness of the anterior abdominal wall. The P450arom transcript level within the core of this endometriotic mass was 4-fold higher than that in the surrounding adipose tissue. It has been shown recently that aromatase expression in various human tissues is regulated by the use of tissue-specific promoters via alternative splicing. To analyze promoter usage, we amplified by RT-PCR the most likely promoter- specific untranslated 5'-termini of P450arom transcripts in 2 endometriotic implants. It appears that these endometriotic implants use both the adipose-type promoter I.4 and gonadal-type promoter II for aromatase expression. The use of promoter I.4 for aromatase expression in adipose tissue has been recently observed to be regulated by members of the interleukin-6 (IL-6) cytokine family. Based on these findings, we examined by RT-PCR, IL-6 and IL-11 messenger RNA expression in 5 endometriotic tissues and 1 eutopic endometrial sample from a patient with endometriosis. We detected IL-6 and IL-11 transcripts in all endometriotic tissues and in the eutopic endometrial tissue sample studied. Our findings indicate that both eutopic endometrial tissues and endometriotic implants from patients with endometriosis are biochemically different from normal endometrial tissues of disease-free women. The presence of aromatase expression in eutopic endometrial tissues from patients with endometriosis may be related to the capability of implantation of these tissues on peritoneal surfaces. Furthermore, the possibility of estrogen production in these implants may serve to promote their growth. Increased IL-6 and IL-11 expression in these tissues suggests that P450arom expression in endometriosis may be regulated in part by these cytokines.


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Hum. Reprod., April 1, 2000; 15(4): 767 - 771.
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A. Akoum, C. Jolicoeur, and A. Boucher
Estradiol Amplifies Interleukin-1-Induced Monocyte Chemotactic Protein-1 Expression by Ectopic Endometrial Cells of Women with Endometriosis
J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 896 - 904.
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G. Leyendecker
Redefining endometriosis: Endometriosis is an entity with extreme pleiomorphism
Hum. Reprod., January 1, 2000; 15(1): 4 - 7.
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G. Kunz, D. Beil, P. Huppert, and G. Leyendecker
Structural abnormalities of the uterine wall in women with endometriosis and infertility visualized by vaginal sonography and magnetic resonance imaging
Hum. Reprod., January 1, 2000; 15(1): 76 - 82.
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H. S. Taylor, C. Bagot, A. Kardana, D. Olive, and A. Arici
HOX gene expression is altered in the endometrium of women with endometriosis
Hum. Reprod., May 1, 1999; 14(5): 1328 - 1331.
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K. Zeitoun, K. Takayama, M. D. Michael, and S. E. Bulun
Stimulation of Aromatase P450 Promoter (II) Activity in Endometriosis and Its Inhibition in Endometrium Are Regulated by Competitive Binding of Steroidogenic Factor-1 and Chicken Ovalbumin Upstream Promoter Transcription Factor to the Same cis-Acting Element
Mol. Endocrinol., February 1, 1999; 13(2): 239 - 253.
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M. Piva and K.L. Sharpe-Timms
Peritoneal endometriotic lesions differentially express a haptoglobin-like gene*
Mol. Hum. Reprod., January 1, 1999; 5(1): 71 - 78.
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K. Zeitoun, K. Takayama, H. Sasano, T. Suzuki, N. Moghrabi, S. Andersson, A. Johns, L. Meng, M. Putman, B. Carr, et al.
Deficient 17{beta}-Hydroxysteroid Dehydrogenase Type 2 Expression in Endometriosis: Failure to Metabolize 17{beta}-Estradiol
J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4474 - 4480.
[Abstract] [Full Text]

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H. Sasano and N. Harada
Intratumoral Aromatase in Human Breast, Endometrial, and Ovarian Malignancies
Endocr. Rev., October 1, 1998; 19(5): 593 - 607.
[Abstract] [Full Text]

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L. Dalla Valle, A. Ramina, S. Vianello, A. Fassina, P. Belvedere, and L. Colombo
Potential for Estrogen Synthesis and Action in Human Normal and Neoplastic Thyroid Tissues
J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3702 - 3709.
[Abstract] [Full Text]

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 EndocrinologyHome page
M. Shozu, Y. Zhao, S. E. Bulun, and E. R. Simpson
Multiple Splicing Events Involved in Regulation of Human Aromatase Expression by a Novel Promoter, I.6
Endocrinology, April 1, 1998; 139(4): 1610 - 1617.
[Abstract] [Full Text] [PDF]

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 BloodHome page
X. Du and D. A. Williams
Interleukin-11: Review of Molecular, Cell Biology, and Clinical Use
Blood, June 1, 1997; 89(11): 3897 - 3908.
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L. S. Noble, K. Takayama, K. M. Zeitoun, J. M. Putman, D. A. Johns, M. M. Hinshelwood, V. R. Agarwal, Y. Zhao, B. R. Carr, and S. E. Bulun
Prostaglandin E2 Stimulates Aromatase Expression in Endometriosis-Derived Stromal Cells
J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 600 - 606.
[Abstract] [Full Text] [PDF]


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