The regional brain distribution of the neurosteroids pregnenolone and pregnenolone sulfate following intravenous infusion

Abstract

We have studied the distribution of the neurosteroids pregnenolone (Pe) and pregnenolone sulfate (PeS) in seven brain regions, and plasma and fat tissues in male adult rats following the intravenous infusion of 14 mg/kg Pe and 18 mg/kg PeS, respectively. After chromatographic separation of steroid sulfate esters and non-conjugated steroids by solid phase octadecyl C18 columns and celite column chromatographic separation of Pe from cross-reacted steroids, the concentrations of Pe and PeS were determined by radioimmunoassay. We found that both Pe and PeS concentrations were significantly increased in plasma, fat and brain compared to the vehicle controls after i.v. infusion of Pe and PeS. In the controls, Pe concentrations were highly correlated within brain regions and between fat and brain regions. Most correlations were lost after Pe and PeS infusions. The content of Pe and PeS was not uniformly distributed in the brain. The hypothalamus contained the highest level of Pe in controls, Pe-infused and PeS-infused rats (12 ± 3.1, 3500 ± 180 and 590 ± 54 ng/g, respectively). The highest concentration of PeS was detected in the hypothalamus (26 ± 8.2 ng/g) and striatum (17 ± 4.1 ng/g) in controls in the hypothalamus (200 ± 24 ng/g) after PeS infusion as well as in the hypothalamus and medulla oblongata (57 ± 9.6 and 55 ± 7.6 ng/g, respectively) after Pe infusion. This study has yielded evidence that PeS injected i.v. can cross the blood-brain barrier without being hydrolysed to the more lipophilic Pe, and can thus be taken up by the brain.