Molecular and Cellular Characterization of the Glutathione Transferases Involved in the Olfactory Metabolism of the Mammary Pheromone

Odorant metabolizing enzymes, considered as critical olfactory perireceptor actors, control the odor molecules reaching the olfactory epithelium by biotransforming them. As an odorant, the mammary pheromone, i.e., 2-methylbut-2-enal (2MB2), emitted in the milk of lactating female rabbits triggers typical nipple searching-grasping behavior through orocephalic movements in newborn rabbits but not in weaned rabbits. We previously showed that 2MB2 perception is significantly modified when its glutathione transferase-dependent olfactory metabolism is affected in newborns. Here, enzymatic assays of the recombinant enzymes GSTA1, M1, and P1 revealed the activity of these enzymes toward the mammary pheromone. Histological experiments revealed strong expression of the GSTA class restricted to the Bowman glands and of GSTP1 in the nuclei of sustentacular cells. Moreover, some modulations of GSTs have been demonstrated, including a significant increase in GSTP1 expression (2-fold in mRNA, pvalue < 0.001; protein, pvalue: 0.031) after 45 min of mammary pheromone exposure at 10–2g/mL and an increase in GSTA expression in weaned rabbits compared with newborn rabbits (3-fold in mRNA, pvalue: 0.011; protein, pvalue: 0.001). Our results provide new insights into the activity, cellular expression, and modulation of the mammary pheromone GST-metabolizing enzymes and clues about their olfactory function.