title: Δ9-Tetrahydrocannabinol targeting estrogen receptor signaling: the possible mechanism of action coupled with endocrine disruption.
abstract: Δ(9)-Tetrahydrocannabinol (Δ(9)-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 Δ(9)-THC's biological activities, its recognized anti-estrogenic activity has been the subject of investigations. Since Δ(9)-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 Δ(9)-THC; dronabinol), it is important to investigate the mechanistic basis underlying the anti-estrogenic activity of Δ(9)-THC. Since Δ(9)-THC has "no" binding potential for estrogen receptor α (ERα) which can be activated by estrogen (E2), the question of how Δ(9)-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 Δ(9)-THC abrogation of E2/ERα-mediated transcriptional activity. Here we discuss the possible mechanism(s) of the Δ(9)-THC-mediated disruption of E2/ERα signaling by presenting our recent findings as well.
authors.affiliation: Laboratory of Xenobiotic Metabolism and Environmental Toxicology, Faculty of Pharmaceutical Sciences, Hiroshima International University (HIU).
authors.forename: Shuso
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000818:Animals; D013759:Dronabinol / Q000494:pharmacology*; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C506487:ESR1 protein, human; D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004958:Estradiol; D013759:Dronabinol