Expression of Aromatase Cytochrome P450 Protein and Messenger Ribonucleic Acid in Human Endometriotic and Adenomyotic Tissues but not in Normal Endometrium1

Abstract

To determine whether local estrogen production takes place in endometriotic or adenomyotic tissues, in eutopic endometrium from patients with endometriosis or adenomyosis, and in normal endometrium, tissue specimens were examined by immunohistochemistry, catalytic activity, and mRNA expression for aromatase cytochrome P450 (P450arom). P450arom was immunohistochemically localized in the cytoplasm of glandular cells of endometriotic and adenomyotic tissues, and of eutopic endometrium from patients with the respective diseases, whereas estrogen receptors and progesterone receptors were localized in the nuclei of the glandular cells and stroma. Aromatase activity in the microsomal fraction of adenomyotic tissues was inhibited by the addition of danazol, aromatase inhibitors, and anti-human placental P450arom monoclonal antibody (mAb3-2C2) in a manner similar to such inhibition in other human tissues. Reverse transcription polymerase chain reaction and Southern blot analysis also revealed P450arom mRNA in these tissues. However, neither P450arom protein activity nor mRNA was detected in endometrial specimens obtained from normal menstruating women with cervical carcinoma in situ but without any other gynecological disease. These results suggest that at a local level, endometriotic and adenomyotic tissues produce estrogens, which may be involved in the tissue growth through interacting with the estrogen receptor.

The effects of dietary phytoestrogens on aromatase activity in human endometrial stromal cells

“…In addition, aromatase activity of vehicle treated endometrial cells was at background levels for the assay and thus supports the view that aromatase is either absent or inhibited in the endometrium from women without endometriosis. Our findings are in agreement with prior studies in which aromatase cytochrome P450 has been reported to be expressed in the endometrium of women with endometriosis but is either absent [4], or expressed at low levels in the endometrium of women without endometriosis [30]. Therefore, the patients in the current study were grouped into two categories: endometriotic and non-endometriotic.…”

“…While the ovaries are the primary source of estrogen in the body, local production of estrogen by other tissues has also been demonstrated in estrogen dependent diseases such as breast cancer [1,2] and endometriosis [3][4][5]. Endometriosis is a common gynecologic disorder that is characterized by the presence of endometrial glands and stroma outside of the uterine cavity.…”

Identification of an Invasive, N-Cadherin-Expressing Epithelial Cell Type in Endometriosis Using a New Cell Culture Model

“…Thus, the presence of aromatase cytochrome P-450 suggests a local estrogen production that may influence the disease. 45,46 Furthermore, endometriotic cell lines also express gp130, the common chain of the interleukin-6 receptor family that is typically found in sections of peritoneal endometriotic lesions (A. Mayer and A. Schreiner, unpublished observation).…”

“…So far, this question can only be answered concerning molecules also found in endometriotic lesions in vivo. Such marker molecules included cytokeratin, 84,85 aromatase P-450, 45,46 estrogen receptor-␣ and -␤, and progesterone receptor. 43 Not only were all three steroid hormone receptors detected by RT-PCR in most of the endometriotic cell lines, but as in endometriotic lesions, they are expressed in low amounts.…”

Polymorphisms and haplotypes of the gene encoding the estrogen-metabolizing CYP19 gene in Korean women: no association with advanced-stage endometriosis

“…Ectopic endometriotic implants respond to ovarian hormonal changes. Local estrogen production in conjunction with circulating estrogen stimulates the growth of endometriosis, which is mediated by the estrogen receptor (Kitawaki et al 1997).…”