Elevated levels of adrenomedullin in eutopic endometrium and plasma from women with endometriosis

Adrenomedullin and mid-regional pro-adrenomedullin levels are elevated in the eutopic endometrium and in plasma of women with endometriosis.

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Volume 109, Issue 6, Pages 1072–1078

Authors:

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.

Abstract:

Objective

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.

Design

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.

Setting

Academic medical centers.

Patient(s)

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.

Intervention(s)

None.

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.

Result(s)

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.

Conclusion(s)

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.


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