Da. Johnson et al., CHRONIC STEROID SULFATASE INHIBITION BY (P-O-SULFAMOYL)-N-TETRADECANOYL TYRAMINE INCREASES DEHYDROEPIANDROSTERONE-SULFATE IN WHOLE-BRAIN, Life sciences, 61(24), 1997, pp. 355-359
Citations number
14
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
Dehydroepiandrosterone sulfate (DHEAS) is a neurosteroid which functio
ns as a negative allosteric modulator of the GABA(A) receptor-gated ch
loride channel. Steroid sulfatase inhibitors including (p-O-sulfamoyl)
-N-tetradecanoyl tyramine (DU-14), can potentiate the blockade of the
amnestic effects of scopolamine by exogenously administered DHEAS. Mor
eover, when administered over a 15 day period, DU-14 can block scopola
mine amnesia without the concurrent administration of DHEAS. Since the
enzyme, steroid sulfatase, facilitates the hydrolysis of the sulfate
moiety from DHEAS, the intent of this study was to determine whether c
hronic administration of DU-14 could increase whole brain concentratio
ns of endogenous DHEAS. Rats were administered DU-14 or corn oil vehic
le for 15 days. Following the last day the animals were sacrificed and
the brains were removed and analyzed for DHEAS content. DU-14 increas
ed the whole brain concentration of DHEAS 77.6%, from 0.65 +/- 0.06 to
1.15 +/- 0.12 mu g/g (mean +/- SEM). This result suggests that steroi
d sulfatase inhibitors may enhance cognitive function following chroni
c treatment by increasing the concentration of excitatory neurosteroid
s such as DHEAS in the brain. Steroid sulfatase inhibitors, therefore,
may provide a novel mechanism for facilitating central nervous system
function. (C) 1997 Elsevier Science Inc.