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.

  • Raul Gomez, PhD, IUIVI

    Wow, terrific work, congratulations to the authors. Their results show such dramatic decrease of CB1 receptor mRNA in response to TCDD and link so well with the “progesterone resistance” effect observed in endometriosis women that I have missed very badly not to see in htis paper the effects exerted by TCDD on CB1 receptors PROTEIN levels.
    1) Might the authors perhaps be willing to discuss OR provide some extra information regarding the effects of TCDD or PR disruption on CB1 protein levels in cultured stromal cells?
    2) What about functionality of CB1 receptor protein? Did the authors check or are they aiming to test whether any of the the compounds assayed affected CB1-R signaling in endometrial cells?
    3) Endocannabinoids have been largely proposed to be effective in pain relief in endometriosis women, on the basis of your findings (decreased CB1 mRNA levels in endometriosis) do you think the therapeutic role of endocannabinoids must be challenged? to which extent?
    Thanks
    Raul Gomez PhD IUIVI

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