Steroid profiling in brain and plasma of male and pseudopregnant female rats after traumatic brain injury: Analysis by gas chromatography/mass spectrometry

Abstract

Steroids in brain arise from the peripheral endocrine glands and local synthesis. In traumatic brain injury (TBI), the endogenous circulating hormones at the time of injury are important for neuroprotection. In particular, pseudopregnant females recover better than males from TBI. We investigated the effect of pseudopregnancy and TBI on steroid levels in plasma and in three brain regions (within, adjacent, and distal to the lesion site), 6 and 24 h after prefrontal cortex injury. The following steroids were analyzed by gas chromatography/ mass spectrometry: pregnenolone, progesterone, 5α-dihydroprogesterone, 3α,5α-tetrahydroprogesterone, 3α,5α-tetrahydroprogesterone, dehydroepiandrosterone, Δ4-androstenedione, testosterone, 5α-dihydrotestosterone, 3α,5α-tetrahydrotestosterone, 3β,5α- tetrahydrotestosterone, and 17β-estradiol. Corticosteronewasassayed in plasma to account for stress in the rats. We found different steroid profiles in brain and plasma of male and pseudopregnant female rats and specific profile changes after TBI. In sham-operated pseudopregnant females, much higher levels of progesterone, 5α-dihydroprogesterone, 3α,5α- tetrahydroprogesterone, and 3β,5α-tetrahydroprogesterone were measured in both brain and plasma, compared with shamoperated males. Plasma levels of corticosterone were high in all groups, indicating that the surgeries induced acute stress. Six hours after TBI, the levels of pregnenolone, progesterone, and 5α-dihydroprogesterone increased, and those of testosterone decreased in male brain, whereas levels of 5α- dihydroprogesterone and 3β,5α-tetrahydroprogesterone increased in brain of pseudopregnant female rats. Plasma levels of 5α- dihydroprogesterone did not change after TBI, suggesting a local activation of the 5α-reduction pathway of progesterone in both male and pseudopregnant female brain. The significant increase in neurosteroid levels in the male brain after TBI is consistent with their role in neuroprotection. In pseudopregnant females, high levels of circulating progestagens may provide protection against TBI. Copyright © 2007 by The Endocrine Society.