DISTRIBUTION OF MEMBRANE PROGESTERONE RECEPTOR ALPHA IN THE MALE MOUSE AND RAT BRAIN AND ITS REGULATION AFTER TRAUMATIC BRAIN INJURY

Progesterone has been shown to exert pleiotropic actions in the brain of both male and females. In particular, after traumatic brain injury (TBI), progesterone has important neuroprotective effects. In addition to intracellular progesterone receptors, membrane receptors of the hormone such as membrane progesterone receptor (mPR) may also be involved in neuroprotection. Three mPR subtypes (mPR alpha, mPR beta and mPR gamma) have been described and mPR alpha is best characterized pharmacologically. In the present study we investigated the distribution, cellular localization and the regulation of mPR alpha in male mouse and rat brain. We showed by reverse transcription-PCR that mPR alpha is expressed at similar levels in the male and female mouse brain suggesting that its expression may not be influenced by steroid levels. Treatment of males by estradiol or progesterone did not modify the level of expression of mPR alpha as shown by Western blot analysis. In situ hybridization and immunohistochemistry analysis showed a wide expression of mPR alpha in particular in the olfactory bulb, striatum, cortex, thalamus, hypothalamus, septum, hippocampus and cerebellum. Double immunofluorescence and confocal microscopy analysis showed that mPR alpha is expressed by neurons but not by oligodendrocytes and astrocytes. In the rat brain, the distribution of mPR alpha was similar to that observed in mouse brain; and after TBI, mPR alpha expression was induced in oligodendrocytes, astrocytes and reactive microglia. The wide neuroanatomical distribution of mPR alpha suggests that this receptor may play a role beyond neuroendocrine and reproductive functions. However, in the absence of injury its role might be restricted to neurons. The induction of mPR alpha after TBI in microglia, astrocytes and oligodendrocytes, points to a potential role in mediating the modulatory effects of progesterone in inflammation, ion and water homeostasis and myelin repair in the injured brain. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.