title: The membrane-associated progesterone-binding protein 25-Dx: expression, cellular localization and up-regulation after brain and spinal cord injuries.
abstract: Progesterone has neuroprotective effects in the injured and diseased spinal cord and after traumatic brain injury (TBI). In addition to intracellular progesterone receptors (PR), membrane-binding sites of progesterone may be involved in neuroprotection. A first putative membrane receptor of progesterone, distinct from the classical intracellular PR isoforms, with a single membrane-spanning domain, has been cloned from porcine liver. Homologous proteins were cloned in rats (25-Dx), mice (PGRMC1) and humans (Hpr.6). We will refer to this progesterone-binding protein as 25-Dx. The distribution and regulation of 25-Dx in the nervous system may provide some clues to its functions. In spinal cord, 25-Dx is localized in cell membranes of dorsal horn neurons and ependymal cells lining the central canal. A role of 25-Dx in mediating the protective effects of progesterone in the spinal cord is supported by the observation that its mRNA and protein are up-regulated by progesterone in dorsal horn of the injured spinal cord. In contrast, the classical intracellular PRs were down-regulated under these conditions. In brain, 25-Dx is particularly abundant in the hypothalamic area, circumventricular organs, ependymal cells of the ventricular walls, and the meninges. Interestingly, it is co-expressed with vasopressin in neurons of the paraventricular, supraoptic and retrochiasmatic nuclei. In response to TBI, 25-Dx expression is up-regulated in neurons and induced in astrocytes. The expression of 25-Dx in structures involved in cerebrospinal fluid production and osmoregulation, and its up-regulation after brain damage, point to a potentially important role of this progesterone-binding protein in the maintenance of water homeostasis after TBI. Our observations suggest that progesterone's actions may involve different signaling mechanisms depending on the pathophysiological context, and that 25-Dx may be involved in the neuroprotective effect of progesterone in the injured brain and spinal cord.
authors.affiliation: Inserm UMR788 and University Paris 11, Kremlin-Bicêtre, France. Rachida.Guennoun@kb.inserm.fr
authors.forename: R
authors.initials: R
authors.lastname: Guennoun
authors.forename: D
authors.initials: D
authors.lastname: Meffre
authors.forename: F
authors.initials: F
authors.lastname: Labombarda
authors.forename: S L
authors.initials: SL
authors.lastname: Gonzalez
authors.forename: M C
authors.initials: MC
authors.lastname: Gonzalez Deniselle
authors.forename: D G
authors.initials: DG
authors.lastname: Stein
authors.forename: A F
authors.initials: AF
authors.lastname: De Nicola
authors.forename: M
authors.initials: M
authors.lastname: Schumacher
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008565:Membrane Proteins; D018696:Neuroprotective Agents; D011980:Receptors, Progesterone; D011374:Progesterone