CONICET | Buscador de Institutos y Recursos Humanos

The recent molecular cloning of membrane receptorsfor progesterone (mPRs) has tremendous implicationsfor understanding the multiple actions of the hormone in thenervous system. The three isoforms which have been clonedfrom several species, mPR, mPR and mPR, have seventransmembranedomains, are G protein-coupled and maythus account for the rapid modulation of many intracellularsignaling cascades by progesterone. However, in order toelucidate the precise functions of mPRs within the nervoussystem it is first necessary to determine their expressionpatterns and also to develop new pharmacological and moleculartools. The aim of the present study was to profile mPRexpression in the mouse spinal cord, where progesteronehas been shown to exert pleiotropic actions on neurons andglial cells, and where the hormone can also be locally synthesized.Our results show a wide distribution of mPR,which is expressed in most neurons, astrocytes, oligodendrocytes,and also in a large proportion of NG2 progenitorcells. This mPR isoform is thus likely to play a major role inthe neuroprotective and promyelinating effects of progesterone.On the contrary, mPR showed a more restricted distribution,and was mainly present in ventral horn motoneuronsand in neurites, consistent with an important role in neuronaltransmission and plasticity. Interestingly, mPR was notpresent in glial cells. These observations suggest that thetwo mPR isoforms mediate distinct and specific functions ofprogesterone in the spinal cord. A significant observationwas their very stable expression, which was similar in bothsexes and not influenced by the presence or absence of theclassical progesterone receptors. Although mPR mRNAcould be detected in spinal cord tissue by reverse transcriptasepolymerase chain reaction (RTPCR), in situ hybridizationanalysis did not allow us to verify and to map its presence,probably due to its relatively low expression. Thepresent study is the first precise map of the regional andcellular distribution of mPR expression in the nervous system,a prior requirement for in vivo molecular and pharmacologicalstrategies aimed to elucidate their precise functions.It thus represents a first important step towards a newunderstanding of progesterone actions in the nervous systemwithin a precise neuroanatomical context.