Steroid Receptor Hormonal Actions of Lavender and Tea Tree Oil Components
Presentation Number: OR22-6
Date of Presentation: March 19, 2018, 2018
J. Tyler Ramsey, B.S., Yin Li, PhD, Yukitomo Arao, PhD, Kenneth Korach, PhD.
NIH-NIEHS, Res Triangle Pk, NC, USA.
Lavender oil (LO) and Tea Tree oil (TTO) are commonly found in multiple hygiene products whose presence has potential environmental health exposures and endocrine disrupting properties. The compositions of these oils are comprised of many components and their actions are purported to reduce stress, aid with sleep, and mitigate negative effects of multiple human diseases. Clinical studies have shown a linkage between prepubertal gynecomastia and LO or TTO commodities when used regularly in adolescent boys. Our previous study demonstrated that these two oils act as hormonal mimics through estrogen receptor alpha (ERα) and the androgen receptor (AR). However, there is still little known about the individual components that constitute these oils. In this study, we selected eight chemicals (Eucalyptol; Euc, 4-Terpineol; 4-Terp, Dipentene/Limonene; Di/Lim, α-Terpineol; α-Terpl, Linalyl acetate; LinA, Linalool; Lin, α-Terpinene; α-Terp, and γ-Terpinene; γ-Terp) which are found in the essential oils to investigate their estrogenic and anti-androgenic activity using in vitro cell models. MCF-7 cells were used to measure changes of endogenous ER-target genes when treated with these chemicals. We found that all chemicals significantly induced GREB1 and CTSD genes. HepG2 cells were transiently transfected with ERα expression and estrogen response element (ERE) reporter plasmids to detect ERα/ERE-mediated transcriptional activity. The results showed that all chemicals, except for Euc, can induce ERα/ERE-mediated activity. Interestingly, when co-transfected with an ER steroid receptor coactivator-2 (SRC-2), the weakly active chemical Euc now induced much greater ERE-mediated activity. Furthermore, to test if LO and TTO bind selectively to the ligand binding domain of ERα (LBD-ERα), HepG2 cells were transfected with the LBD-ERα containing SRC-2. The results for both oils increased co-activator recruitment of SRC-2, which activated the LBD-ERα comparable to estradiol. MDA-kb2 cells were used to measure changes of endogenous AR-target genes when treated with these chemicals. We found LinA, Lin, 4-Terp, and α-Terpl significantly downregulated CYP4F8, UGT2B28, SEC14L2, and C1orf116 when co-treated with Testosterone. Interestingly, α-Terp and γ-Terp significantly downregulated all genes except for UGT2B28 and no significant downregulation was observed with Euc except with C1orf116. Therefore, our study has identified eight components of LO and TTO as endocrine disruptor chemicals (EDCs). They demonstrate varying activities depending upon the assay, showing activation of ERα and antagonism of AR; thereby potentially contributing to stimulating clinically relevant mammary gland conditions involving hormonal EDCs.
J. Ramsey: None. Y. Li: None. Y. Arao: None. K. Korach: None.