Smells Like a Hormone?

Science Signaling  03 Nov 2009:
Vol. 2, Issue 95, pp. ec356
DOI: 10.1126/scisignal.295ec356

Odor perception depends on odorant binding to cell surface odorant receptors [OR, members of a large family of G protein–coupled receptors (GPCRs)] and the consequent stimulation of intracellular signaling pathways in sensory neurons. Noting that many odorants are small hydrophobic molecules that can permeate cell membranes, Pick et al. wondered whether odorants might also act intracellularly to trigger additional cellular responses. Screening an odorant library revealed that two structurally distinct classes of odorants [methyl 2,4-dihydroxy-3,6-dimethylbenzoate (or MC, for Mousse Cristal) and synthetic sandalwood compounds] stimulated the translocation of a fluorescently tagged form of estrogen receptor α (ER) from the cytoplasm to the nucleus and decreased its mobility, effects consistent with estrogenic activity. Moreover, both MC and the sandalwood-family odorants Javanol and Polysantol stimulated the ER-dependent transcription of a gene reporter in MCF7 breast cancer cells, as well as MCF7 cell proliferation, as did androstenol (a porcine pheromone with a musk- and sandalwood-like odor). MC also acted as an agonist for the mouse eugenol odorant receptor mOR-EC, stimulating a cAMP-dependent gene reporter as potently as the known mOR-EC ligand eugenol (an odorant in clove oil) did, whereas the sandalwood odorants did not. The authors thus conclude that some odorants can activate both ORs and ERs and, although the estrogenic potency of the odorants was far less than that of 17β-estradiol, noted potential concerns associated with ongoing exposure to compounds with estrogenic activity.

H. Pick, S. Etter, O. Baud, R. Schmauder, L. Bordoli, T. Schwede, H. Vogel, Dual activities of odorants on olfactory and nuclear hormone receptors. J. Biol. Chem. 284, 30547–30555 (2009). [Abstract] [Full Text]