The membrane-associated progesterone-binding protein 25-Dx: expression, cellular localisation and up-regulation after brain and spinal cord injuries

GUENNOUN R; MEFFRE D; LABOMBARDA F; GONZALEZ SL; GONZALEZ DENISELLE MC; STEIN DG; DE NICOLA A. F.; SCHUMMACHER M

BRAIN RESEARCH REVIEWS

ELSEVIER SCIENCE BV

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 (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 systemmay 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 downregulated 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.