THE REGIONAL BRAIN DISTRIBUTION OF THE NEUROSTEROIDS PREGNENOLONE ANDPREGNENOLONE SULFATE FOLLOWING INTRAVENOUS-INFUSION

We have studied the distribution of the neurosteroids pregnenolone (Pe ) and pregnenolone sulfate (PeS) in seven brain regions, and plasma an d fat tissues in male adult rats following the intravenous infusion of 14 mg/kg Pe and 18 mg/kg PeS, respectively. After chromatographic sep aration of steroid sulfate esters and non-conjugated steroids by solid phase octadecyl C18 columns and celite column chromatographic separat ion of Pe from cross-reacted steroids, the concentrations of Pe and Pe S were determined by radioimmunoassay. We found that both Pe and PeS c oncentrations were significantly increased in plasma, fat and brain co mpared to the vehicle controls after i.v. infusion of Pe and PeS. In t he controls, Pe concentrations were highly correlated within brain reg ions and between fat and brain regions. Most correlations were lost af ter 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 oblongat a (57 +/- 9.6 and 55 +/- 7.6 ng/g, respectively) after Pe infusion. Th is study has yielded evidence that PeS injected i.v. can cross the blo od-brain barrier without being hydrolysed to the more lipophilic Pe, a nd can thus be taken up by the brain. (C) 1997 Elsevier Science Ltd.