Δ9-Tetrahydrocannabinol Targeting Estrogen Receptor Signaling : The Possible Mechanism of Action Coupled with Endocrine Disruption

• Published in: Biological and Pharmaceutical Bulletin Vol. 37; no. 9; pp. 1435 - 1438
• Main Author: Shuso Takeda
• Format: Journal Article
• Language: Japanese
• Published: Pharmaceutical Society of Japan 01.09.2014
• ISSN: 0918-6158

Δ9-Tetrahydrocannabinol (Δ9-THC), a biologically active constituent of marijuana, possesses a wide variety of pharmacological and toxicological effects (e.g., analgesia, hypotension, reduction of inflammation, and anti-cancer effects). Among Δ9-THC's biological activities, its recognized anti-estrogenic activity has been the subject of investigations. Since Δ9-THC is used as both a drug of abuse (marijuana) and as a preventive therapeutic to treat pain and nausea in cancer patients undergoing chemotherapy in the United States and other countries (synthesized Δ9-THC; dronabinol), it is important to investigate the mechanistic basis underlying the anti-estrogenic activity of Δ9-THC. Since Δ9-THC has "no" binding potential for estrogen receptor α (ERα) which can be activated by estrogen (E2), the question of how Δ9-THC exerts its inhibitory effect on ERα is not resolved. We have recently reported that ERβ, a second type of ER, is involved in the Δ9-THC abrogation of E2/ERα-mediated transcriptional activity. Here we discuss the possible mechanism(s) of the Δ9-THC-mediated disruption of E2/ERα signaling by presenting our recent findings as well.