The membrane-associated progesterone-binding protein 25-Dx: Expression, cellular

GUENNOUN R.; MEFFRE D.; LABOMBARDA F.; GONZALEZ S.; GONZALEZ DENISELLE M.C.; STEIN D.; DE NICOLA A.F.; SCHUMACHER M

BRAIN RESEARCH REVIEWS

Elsevier

Lugar: Holanda; Año: 2008 vol. 57 p. 493 - 505

0165-0173

Progesterone has neuroprotective effects in the injured and diseased spinal cord and after traumatic brain injury (TBI). In addition to intracellular progesterone receptors, 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 first cloned from rat and porcine liver. Homologous proteins were cloned in rat (named 25-Dx), mice (PGRMC1) and humans (Hpr.6). We shall refer to this progesterone binding protein as 25-Dx, to distinguish it from the progesterone membrane receptors (mPRs) which have later been cloned. The distribution and regulation of 25-Dx in the nervous system may provide some clues concerning its functions. In spinal cord, 25-Dx is localised in cell membranes of dorsal horn neurones and ependymal cells lining the central canal. A role of 25-Dx in mediating 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. On the contrary, the classical intracellular progesterone receptors (PR) were down-regulated under these conditions. In brain, 25-Dx is present in the microsomal and mitochondrial cell fractions. 25-Dx is particularly abundant in the hypothalamic area, circumventricular organs, ependymal cells of the ventricular walls, and in the meninges. Interestingly, it is co-expressed with vasopressin in neurones of the paraventricular, supraoptic and retrochiasmatic nuclei. In response to TBI, 25-Dx expression is up-regulated in neurones and induced in astrocytes. The expression of 25-Dx in structures involved in cerebrospinal fluid production and in 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 actions may involve different signalling 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.