Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat.

ABSTRACT: Little is known about the origin of the neuroactive steroids dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulphate (PregS) in the brain or of their subsequent metabolism. Using rat brain perfusion in situ, we have found ³ H-PregS to enter more rapidly than ³ H-DHEAS and both to undergo extensive (> 50%) desulphation within 0.5 min of uptake. Enzyme activity for the steroid sulphatase catalysing this deconjugation was enriched in the capillary fraction of the blood-brain barrier and its mRNA expressed in cultures of rat brain endothelial cells and astrocytes. Although permeability measurements suggested a net efflux, addition of the efflux inhibitors GF120918 and/or MK571 to the perfusate reduced rather than enhanced the uptake of ³ H-DHEAS and <

SUBMITTER: Qaiser MZ 

PROVIDER: S-EPMC5601180 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature