Membrane progesterone receptors (mPRs) localisation in the mouse spinal. Neuroscience

• Autores: Labombarda, Maria Florencia; Meffre, D; Delespierre, B; Krivokapic Blondiaux, S.; Chastre, A.; Thomas, P.; Pang, Y.; Lydon, J. P.; Gonzalez, Susana Laura; de Nicola, Alejandro Federico; Schumacher, Michael; Gennoun, Rachida
• Año de publicación: 2010
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Membrane Progesterone Receptor; Progesterone; Spinal Cord
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

The recent molecular cloning of membrane receptors for progesterone (mPRs) has tremendous implications for understanding the multiple actions of the hormone in the nervous system. The three isoforms which have been cloned from several species, mPRalpha, mPRbeta and mPRgamma, have seven-transmembrane domains, are G protein-coupled and may thus account for the rapid modulation of many intracellular signaling cascades by progesterone. However, in order to elucidate the precise functions of mPRs within the nervous system it is first necessary to determine their expression patterns and also to develop new pharmacological and molecular tools. The aim of the present study was to profile mPR expression in the mouse spinal cord, where progesterone has been shown to exert pleiotropic actions on neurons and glial cells, and where the hormone can also be locally synthesized. Our results show a wide distribution of mPRalpha, which is expressed in most neurons, astrocytes, oligodendrocytes, and also in a large proportion of NG2(+) progenitor cells. This mPR isoform is thus likely to play a major role in the neuroprotective and promyelinating effects of progesterone. On the contrary, mPRbeta showed a more restricted distribution, and was mainly present in ventral horn motoneurons and in neurites, consistent with an important role in neuronal transmission and plasticity. Interestingly, mPRbeta was not present in glial cells. These observations suggest that the two mPR isoforms mediate distinct and specific functions of progesterone in the spinal cord. A significant observation was their very stable expression, which was similar in both sexes and not influenced by the presence or absence of the classical progesterone receptors. Although mPRgamma mRNA could be detected in spinal cord tissue by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization analysis did not allow us to verify and to map its presence, probably due to its relatively low expression. The present study is the first precise map of the regional and cellular distribution of mPR expression in the nervous system, a prior requirement for in vivo molecular and pharmacological strategies aimed to elucidate their precise functions. It thus represents a first important step towards a new understanding of progesterone actions in the nervous system within a precise neuroanatomical context.
Fil: Labombarda, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Inserm; Francia. Universite Paris Sud; Francia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Meffre, D. Inserm; Francia. Universite Paris Sud; Francia
Fil: Delespierre, B. Inserm; Francia. Universite Paris Sud; Francia
Fil: Krivokapic Blondiaux, S.. Inserm; Francia. Universite Paris Sud; Francia
Fil: Chastre, A.. Inserm; Francia. Universite Paris Sud; Francia
Fil: Thomas, P.. University of Texas at Austin; Estados Unidos
Fil: Pang, Y.. University of Texas at Austin; Estados Unidos
Fil: Lydon, J. P.. Baylor College of Medicine; Estados Unidos
Fil: Gonzalez, Susana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: de Nicola, Alejandro Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina
Fil: Schumacher, Michael. Inserm; Francia. Universite Paris Sud; Francia
Fil: Gennoun, Rachida. Inserm; Francia. Universite Paris Sud; Francia