Effects of injury and progesterone treatment on progesterone receptor and progesterone binding protein 25-Dx expression in the rat spinal cord.

LABOMBARDA F; GONZALEZ SL; GONZALEZ DENISELLE, MC; VINSON GP; SCHUMACHER M; DE NICOLA AF; GUENNOUN R

JOURNAL OF NEUROCHEMISTRY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2003 p. 902 - 913

0022-3042

Progesterone provides neuroprotection after spinal cord injury,but the molecular mechanisms involved in this effect are notcompletely understood. In this work, expression of two bindingproteins for progesterone was studied in intact and injured ratspinal cord: the classical intracellular progesterone receptor(PR) and 25-Dx, a recently discovered progesterone membranebinding site. RT-PCR was employed to determine theirrelative mRNA levels, whereas cellular localization and relativeprotein levels were investigated by immunocytochemistry. Weobserved that spinal cord PR mRNA was not up-regulated byestrogen in contrast to what is observed in many brain areasand in the uterus, but was abundant as it amounted to a third ofthat measured in the estradiol-stimulated uterus. In male ratswith complete spinal cord transection, levels of PR mRNA weresignificantly decreased, while those of 25-Dx mRNA remainedunchanged with respect to control animals. When spinal cordinjuredanimals received progesterone treatment during 72 h,PR mRNA levels were not affected and remained low, whereas25-Dx mRNA levels were significantly increased. Immunostainingof PR showed its intracellular localization in bothneurons and glial cells, whereas 25-Dx immunoreactivity waslocalized to cell membranes of dorsal horn and central canalneurons. As the two binding proteins for progesterone differwith respect to their response to lesion, their regulation byprogesterone, their cellular and subcellular localizations, theirfunctions may differ under normal and pathological conditions.These observations point to a novel and potentially importantrole of the progesterone binding protein 25-Dx after injury ofthe nervous system and suggest that the neuroprotective effectsof progesterone may not necessarily be mediated by theclassical progesterone receptor but may involve distinctmembrane binding sites.