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

• Published in: Biology of reproduction 2009, Vol.80 (1), p.105-114
• Main Authors: Aghajanova, L, Hamilton, A, Kwintkiewicz, J, Vo, K.C, Giudice, L.C
• Format: Article
• Language: English
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Adult; Aromatase - biosynthesis; Aromatase - genetics; Aromatase - metabolism; Biological and medical sciences; Decidua - enzymology; Decidua - metabolism; Endometriosis - enzymology; Endometriosis - metabolism; Endometriosis - pathology; Endometrium - cytology; Endometrium - drug effects; Endometrium - enzymology; Endometrium - metabolism; Enzyme-Linked Immunosorbent Assay; Estradiol - biosynthesis; Estradiol Dehydrogenases - biosynthesis; Estradiol Dehydrogenases - genetics; Estradiol Dehydrogenases - metabolism; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Insulin-Like Growth Factor Binding Protein 1 - metabolism; Medical sciences; Middle Aged; Non tumoral diseases; Progesterone - biosynthesis; Progesterone - pharmacology; Prolactin - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Stromal Cells - drug effects; Stromal Cells - enzymology; Stromal Cells - metabolism; Stromal Cells - pathology; Young Adult
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.108.070300

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.