Progesterone dependent Regulation of Endometrial Cannabinoid Receptor Type 1 CB1-R mRNA Expression is Disrupted in Women with Endometriosis and in Isolated Stromal Cells Exposed to …

Capsule:
Endometrial cannabinoid receptor type 1 expression during the progesterone-dominant secretory phase is minimal in women with endometriosis, and exposure of endometrial cells to TCDD similarly disrupts cannabinoid signaling.

Authors:
David Resuehr, Ph.D., Dana Glore, B.S., Hugh S. Taylor, M.D., Ph.D., Kaylon L. Bruner-Tran, Ph.D., Kevin G. Osteen, Ph.D.

Volume 98, Issue 4, Pages 948-956.e1, October 2012

Abstract:

Objective:
To examine the differentiation-related expression of CB1-R mRNA and protein in endometrial tissue obtained from women with and without endometriosis and to determine the impact of acute TCDD exposure on CB1-R gene expression in isolated endometrial stromal cells.

Design:
Laboratory-based study.

Setting:
University-affiliated medical center.

Patients:
Women with and without endometriosis undergoing volunteer endometrial biopsies after informed consent.

Interventions:
None.

Main Outcome Measures:
Analysis of in vivo CB1-R mRNA and protein expression in human endometrial tissues and mRNA expression in isolated stromal cells following exposure to TCDD or a progesterone receptor antagonist (Onapristone).

Results:
Expression of CB1-R mRNA and protein was highest during the progesteronedominated secretory phase in control women, while expression was minimal in endometrial tissues acquired from women with endometriosis, regardless of the cycle phase. Although progesterone was found to induce CB1-R mRNA expression in endometrial stromal cells from control donors, steroid-induced expression of this gene was inhibited by co-treatment with either TCDD or Onapristone.

Conclusions:
Our studies reveal a role for the anti-inflammatory actions of progesterone in regulating endometrial cannabinoid signaling, which is disrupted in women with endometriosis. Significantly, our studies demonstrate, for the first time, that acute TCDD exposure disrupts cannabinoid signaling in the human endometrium.

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