Effects of adult female rat androgenization on brain morphology and metabolomic profile

Androgenization in adult natal women, as in transsexual men (TM), affects brain cortical thickness and the volume of subcortical structures. In order to understand the mechanism underlying these changes we have developed an adult female rat model of androgenization. Magnetic resonance imaging and spectroscopy were used to monitor brain volume changes, white matter microstructure and ex vivo metabolic profiles over 32 days in androgenized and control subjects. Supraphysiological doses of testosterone prevents aging decrease of fractional anisotropy values, decreased general cortical volume and the relative concentrations of glutamine (Gln) and myo-Inositol (mI). An increase in the N-acetylaspartate (NAA)/mI ratio was detected d. Since mI and Gln are astrocyte markers and osmolytes, we suspect that the anabolic effects of testosterone change astrocyte osmolarity so as to extrude Mi and Gln from these cells in order to maintain osmotic homeostasis. This mechanism could explain the brain changes observed in TM and other individuals receiving androgenic anabolic steroids.Grants (MICINN-PSI2014-58004-P to A.G.), and grant (SAF-2014-53739-R to S.C.).Peer reviewe