Effects of testosterone on Interleukin-6 expression in astrocytes

BELLINI MJ; LÓPEZ IBAÑEZ DE ALDECOA A; GARCIA-SEGURA LM

TORINO, ITALIA

Congreso; 6th International Meeting STEROIDS AND NERVOUS SYSTEM; 2011

Astrocyte-derived interleukin-6 (IL-6) is involved in the control of glial and neuronal differentiation and reactive gliosis [1-3]. Previous studies have shown that testosterone reduces reactive gliosis in the brain after a stab wound injury [4]. In this study we have assessed whether testosterone regulates the expression of IL-6 in primary cultures of astrocytes. Methods: Astrocyte cultures were prepared by mechanical dissociation of the cerebral cortex from newborn CD1 mice [5]. One day after seeding, astrocytes were treated for 24 h with 10-9 to 10-6 testosterone or vehicle. In addition, some cultures were treated with 10-6 testosterone in presence or absence of 10-6 flutamide (antagonist of androgen receptors), 10-5 finasteride (5-alpha reductase inhibitor) or 10-6 letrozole (aromatase inhibitor). Results: Testosterone reduced IL-6 mRNA levels in astrocytes. The effect of testosterone was dose dependent and was not affected by flutamide, finasteride or letrozole. Flutamide per se reduced IL-6 levels while letrozole per se increased IL-6 levels. Conclusions: Our findings suggest that testosterone regulates IL-6 expression in astrocytes by a mechanism that is independent of its conversion to estradiol or dihidrotestosterone and that is not mediated by classical androgen receptors.1. Islam O, Gong X, Rose-John S, Heese K. Interleukin-6 and neural stem cells: more than gliogenesis. Mol Biol Cell. 2009 Jan;20(1):188-99.2. Oh J, McCloskey MA, Blong CC, Bendickson L, Nilsen-Hamilton M, Sakaguchi DS. Astrocyte-derived interleukin-6 promotes specific neuronal differentiation of neural progenitor cells from adult hippocampus. J Neurosci Res. 2010 Oct;88(13):2798-809.3. Vallières L, Campbell IL, Gage FH, Sawchenko PE. Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6. J Neurosci. 2002 Jan 15;22(2):486-92.4. Barreto G, Veiga S, Azcoitia I, Garcia-Segura LM, Garcia-Ovejero D.Testosterone decreases reactive astroglia and reactive microglia after brain injury in male rats: role of its metabolites, oestradiol and dihydrotestosterone. Eur J Neurosci. 2007 May;25(10):3039-46.5. Cerciat M, Unkila M, Garcia-Segura LM, Arevalo MA. Selective estrogen receptor modulators decrease the production of interleukin-6 and interferon-gamma-inducible protein-10 by astrocytes exposed to inflammatory challenge in vitro. Glia. 2010 Jan 1;58(1):93-102.