Progesterone-dependent regulation of endometrial cannabinoid receptor type 1 (CB1-R) expression is disrupted in women with endometriosis and in isolated stromal cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Abstract

Objective: To examine the differentiation-related expression of cannabinoid receptor type 1 (CB1-R) messenger RNA (mRNA) and protein in endometrial tissue obtained from women with and without endometriosis and to determine the impact of acute 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on CB1-R gene expression in isolated endometrial stromal cells.

Design: Laboratory-based study.

Setting: University-affiliated medical center.

Patient(s): Women with and without endometriosis undergoing volunteer endometrial biopsies after informed consent.

Intervention(s): None.

Main outcome measure(s): Analysis of in vivo CB1-R mRNA and protein expression in human endometrial tissues and mRNA expression in isolated stromal cells after exposure to TCDD or a progesterone receptor antagonist (onapristone).

Result(s): Expression of CB1-R mRNA and protein was highest during the progesterone-dominated secretory phase in control samples, but expression was minimal in the 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 cotreatment with either TCDD or onapristone.

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