Elevated levels of adrenomedullin in eutopic endometrium and plasma from women with endometriosis
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Brooke C. Matson, Ph.D., Kelsey E. Quinn, Ph.D., Bruce A. Lessey, M.D., Ph.D., Steven L. Young, M.D., Ph.D., Kathleen M. Caron, Ph.D.
To test adrenomedullin (Adm, ADM) as a downstream target of signal transducer and activator of transcription 3 (STAT3) in endometrial cells and to test midregional proadrenomedullin (MR-proADM) as a biomarker of endometriosis.
Cross-sectional analysis of Adm expression in eutopic endometrium and of MR-proADM in plasma from women with and without endometriosis; and prospective study of MR-proADM levels in women with endometriosis undergoing surgical resection of ectopic lesions.
Academic medical centers.
Fifteen patients with endometriosis and 11 healthy control subjects who donated eutopic endometrial biopsies; and 28 patients with endometriosis and 19 healthy control subjects who donated plasma for MR-proADM analysis.
Main Outcome Measure(s)
Adm mRNA levels according to quantitative real-time polymerase chain reaction after activation of STAT3 by interleukin-6 (IL-6) in Ishikawa cells; immunohistochemistry for ADM in eutopic endometrial biopsies from women with endometriosis compared with healthy donors; and MR-proADM levels measured by commercial immunoassay in plasma from healthy women and women with endometriosis who subsequently underwent surgical resection of ectopic lesions.
Activation of STAT3 by IL-6 up-regulated Adm mRNA expression in Ishikawa cells. ADM protein levels were elevated in the eutopic endometrium of women with endometriosis. MR-proADM concentrations were higher in women with endometriosis but were not correlated with disease stage, corrected by surgery, or predictive of fertility outcome.
MR-proADM may be able to serve as a biomarker of endometriosis, but it is unknown whether elevated MR-proADM levels are secondary to the estrogenic and inflammatory properties of endometriosis or an inciting pathogenic factor.