RESUMEN
Evidence that endogenous progesterone (PROG) is neuroprotective after traumatic brain injury (TBI) is supported by the findings that pseudopregnant female rats present less edema and achieve better functional recovery than do male rats. PROG in the nervous system may originate from steroidogenic glands or can be locally synthesized. 3beta-Hydroxysteroid dehydrogenase/5-ene-4-ene isomerase (3beta-HSD) is the key enzyme in the biosynthesis of PROG. In the present study, we investigated the effects of pseudopregnancy and TBI on brain 3beta-HSD mRNA expression and on PROG levels. Twenty-four hours after bilateral contusion of the medial prefrontal cortex of rats, 3beta-HSD mRNA expression was analyzed by in situ hybridization while PROG levels were measured by gas chromatography/mass spectrometry. Similar levels of 3beta-HSD mRNA expression were observed in males and pseudopregnant females in the non-injured groups. At this time point, there was a significant decrease in the 3beta-HSD mRNA expression in the contusion site within the frontal cortex in both males and pseudopregnant females. In all other regions analyzed, 3beta-HSD mRNA expression was not affected by TBI and there was no difference between males and pseudopregnant females. The high decrease in the expression of the 3beta-HSD mRNA in the lesion site 24 h after TBI suggests a possible decrease in locally synthesized PROG in lesion site without change in the other brain regions. This decrease has less impact in pseudopregnant females since they have high plasmatic and brain levels of PROG compared to males.
Asunto(s)
Lesiones Encefálicas/enzimología , Encéfalo/enzimología , Complejos Multienzimáticos/genética , Progesterona Reductasa/genética , Seudoembarazo/enzimología , Esteroide Isomerasas/genética , Animales , Encéfalo/metabolismo , Química Encefálica , Lesiones Encefálicas/patología , Femenino , Regulación Enzimológica de la Expresión Génica , Masculino , Modelos Biológicos , Complejos Multienzimáticos/metabolismo , Progesterona/análisis , Progesterona/sangre , Progesterona Reductasa/metabolismo , Seudoembarazo/patología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Esteroide Isomerasas/metabolismoRESUMEN
After traumatic brain injury, progesterone has important neuroprotective effects in the nervous system. There is better functional outcome and less oedema formation in pseudopregnant rat females (high levels of endogenous progesterone) than in males. In addition to intracellular progesterone receptors, membrane binding sites of the hormone such as 25-Dx may also be involved in neuroprotection. In the present study we investigated the distribution of the membrane-associated progesterone-binding protein 25-Dx in rat brain. Immunohistochemical analysis showed that 25-Dx is particularly abundant in the hypothalamic area, circumventricular organs, and ependymal cells of the lateral walls of the third and lateral ventricles. A strong signal was also detected in the meninges. Double immunofluorescence immunolabelling and confocal microscopy showed that 25-Dx is co-expressed with vasopressin in neurones of the paraventricular, supraoptic and retrochiasmatic nuclei. Levels of 25-Dx expression were higher in pseudopregnant females than in males. After traumatic brain injury, 25-Dx expression was up-regulated in neurones and induced in astrocytes, which play an important role in regulating water and ion homeostasis. The expression of 25-Dx in structures involved in CSF production (choroid plexus) and in osmoregulation (circumventricular organs, hypothalamus and meninges), and its up-regulation after brain damage, point to a novel and potentially important role of this progesterone-binding protein in the maintenance of water homeostasis after traumatic brain injury.
