Molecular and Cellular\nCharacterization of the Glutathione\nTransferases Involved in the Olfactory Metabolism of the Mammary Pheromone

Odorant metabolizing enzymes, considered as critical\nolfactory\nperireceptor actors, control the odor molecules reaching the olfactory\nepithelium by biotransforming them. As an odorant, the mammary pheromone,\ni.e., 2-methylbut-2-enal (2MB2), emitted in the milk of lactating\nfemale rabbits triggers typical nipple searching-grasping behavior\nthrough orocephalic movements in newborn rabbits but not in weaned\nrabbits. We previously showed that 2MB2 perception is significantly\nmodified when its glutathione transferase-dependent olfactory metabolism\nis affected in newborns. Here, enzymatic assays of the recombinant\nenzymes GSTA1, M1, and P1 revealed the activity of these enzymes toward\nthe mammary pheromone. Histological experiments revealed strong expression\nof the GSTA class restricted to the Bowman glands and of GSTP1 in\nthe nuclei of sustentacular cells. Moreover, some modulations of GSTs\nhave been demonstrated, including a significant increase in GSTP1\nexpression (2-fold in mRNA, <i>p</i> value < 0.001; protein, <i>p</i> value: 0.031) after 45 min of mammary pheromone exposure\nat 10<sup>–2</sup> g/mL and an increase in GSTA expression\nin weaned rabbits compared with newborn rabbits (3-fold in mRNA, <i>p</i> value: 0.011; protein, <i>p</i> value: 0.001).\nOur results provide new insights into the activity, cellular expression,\nand modulation of the mammary pheromone GST-metabolizing enzymes and\nclues about their olfactory function.