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

MEFFRE D.; LABOMBARDA F; DELESPIERRE B.; CHASTRE A.; DE NICOLA A.F.; STEIN D.; SCHUMACHER M; GUENNOUN R

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2013 vol. 231 p. 111 - 124

0306-4522

Abstract—Progesterone has been shown to exert pleiotropicactions in the brain of both male and females. In particular,after traumatic brain injury (TBI), progesterone hasimportant neuroprotective effects. In addition to intracellularprogesterone receptors, membrane receptors of the hormonesuch as membrane progesterone receptor (mPR)may also be involved in neuroprotection. Three mPR subtypes(mPRa, mPRb, and mPRc) have been described andmPRa is best characterized pharmacologically. In the presentstudy we investigated the distribution, cellular localizationand the regulation of mPRa in male mouse and ratbrain. We showed by reverse transcription-PCR that mPRais expressed at similar levels in the male and female mousebrain suggesting that its expression may not be influencedby steroid levels. Treatment of males by estradiol or progesteronedid not modify the level of expression of mPRa asshown by Western blot analysis. In situ hybridization andimmunohistochemistry analysis showed a wide expressionof mPRa in particular in the olfactory bulb, striatum, cortex,thalamus, hypothalamus, septum, hippocampus and cerebellum.Double immunofluorescence and confocal microscopyanalysis showed that mPRa is expressed by neuronsbut not by oligodendrocytes and astrocytes. In the rat brain,the distribution of mPRa was similar to that observed inmouse brain; and after TBI, mPRa expression was inducedin oligodendrocytes, astrocytes and reactive microglia.The wide neuroanatomical distribution of mPRa suggeststhat this receptor may play a role beyond neuroendocrineand reproductive functions. However, in the absence ofinjury its role might be restricted to neurons. The inductionof mPRa after TBI in microglia, astrocytes and oligodendrocytes,points to a potential role in mediating the modulatoryeffects of progesterone in inflammation, ion and waterhomeostasis and myelin repair in the injured brain. 2012 IBRO. Published by Elsevier Ltd. All rights reserved.Key words: membrane progesterone receptor (mPR), neurons,astrocytes, oligodendrocytes, microglia, traumatic braininjury (TBI).