HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 80/1/105    most recent biolreprod.108.070300v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal My Folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aghajanova, L. Articles by Giudice, L.C. Search for Related Content PubMed PubMed Citation Articles by Aghajanova, L. Articles by Giudice, L.C. Agricola Articles by Aghajanova, L. Articles by Giudice, L.C.

Steroidogenic Enzyme and Key Decidualization Marker Dysregulation in Endometrial Stromal Cells from Women with Versus Without Endometriosis¹

Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California 94143

ABSTRACT

Identification of mechanisms underlying endometriosis pathogenesis will facilitate understanding and treatment of infertility and pain associated with this disorder. Herein, we investigated the expression of steroidogenic pathway enzymes and key decidualization biomarkers in endometrial tissue and in eutopic endometrial stromal fibroblasts (hESFs) from women with vs. those without endometriosis, and subsequently treated in vitro with 8-bromo-cAMP (8-Br-cAMP) or progesterone (P₄). Real-time quantitative PCR, immunohistochemistry, ELISA, and radiometric aromatase activity assay were used. The results demonstrate significantly increased (14.5-fold; P = 0.037) expression of aromatase in eutopic endometrium of women with disease. In 8-Br-cAMP-treated hESF from eutopic endometrium of women with endometriosis, the balance in estradiol (E₂) and P₄ biosynthetic and metabolizing enzymes is disturbed (decreased HSD3B1 and HSD17B2, and increased HSD17B1 and aromatase), with the equilibrium being shifted towards an E₂-enriched milieu. However, hESF from the same group of women treated with P₄ did not demonstrate such responsiveness. Lower expression of IGFBP1 and prolactin mRNA and protein was observed in hESF from women with vs. those without endometriosis in response to 8-Br-cAMP, but not P₄, suggesting a blunted response of these decidual biomarkers to activation of the PKA pathway in eutopic endometrium in women with disease. The dichotomy of 8-Br-cAMP regulation of select steroidogenic enzymes leading to an enriched E₂ milieu within the endometrium and a blunted response of decidual biomarkers to this decidualizing agent of hESF from women with endometriosis suggests resistance to full decidualization of the stromal fibroblasts and mechanisms underlying implantation failure and the pathophysiology of this disorder.

endometrial fibroblasts, endometriosis, eutopic endometrium, steroidogenesis

¹Supported by the National Institute of Child Health and Human Development/National Institutes of Health through cooperative agreement 1U54HD055764-01 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research.

Correspondence: ²Linda C. Giudice, Department of Obstetrics, Gynecology and Reproductive Sciences, The Robert B. Jaffe, MD Endowed Professor in the Reproductive Sciences, University of California, San Francisco, 505 Parnassus Ave., M1496, Box 0132, San Francisco, CA 94143-0132. FAX: 415 476 1811; e-mail: giudice{at}obgyn.ucsf.edu

This article has been cited by other articles:

				S. Colette, J.C. Lousse, S. Defrere, M. Curaba, J.F. Heilier, A. Van Langendonckt, M. Mestdagt, J.M. Foidart, E. Loumaye, and J. Donnez Absence of aromatase protein and mRNA expression in endometriosis Hum. Reprod., June 2, 2009; (2009) dep199v1. [Abstract] [Full Text] [PDF]