title: Steroid sulfatase (STS) expression in the human temporal lobe: enzyme activity, mRNA expression and immunohistochemistry study.
abstract: Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are suggested to be important neurosteroids. We investigated steroid sulfatase (STS) in human temporal lobe biopsies in the context of possible cerebral DHEA(S) de novo biosynthesis. Formation of DHEA(S) in mature human brain tissue has not yet been studied. 17 alpha-Hydroxylase/C17-20-lyase and hydroxysteroid sulfotransferase catalyze the formation of DHEA from pregnenolone and the subsequent sulfoconjugation, respectively. Neither their mRNA nor activity were detected, indicating that DHEA(S) are not produced within the human temporal lobe. Conversely, strong activity and mRNA expression of DHEAS desulfating STS was found, twice as high in cerebral neocortex than in subcortical white matter. Cerebral STS resembled the characteristics of the known placental enzyme. Immunohistochemistry revealed STS in adult cortical neurons as well as in fetal and adult Cajal-Retzius cells. Organic anion transporting proteins OATP-A, -B, -D, and -E showed high mRNA expression levels with distinct patterns in cerebral neocortex and subcortical white matter. Although it is not clear whether they are expressed at the blood-brain barrier and facilitate an influx rather than an efflux, they might well be involved in the transport of steroid sulfates from the blood. Therefore, we hypothesize that DHEAS and/or other sulfated 3beta-hydroxysteroids might enter the human temporal lobe from the circulation where they would be readily converted via neuronal STS activity.
authors.affiliation: Department of Pharmacology, University of Pennsylvannia, Philadelphia, Pennsylvannia 19104-6084, USA. st_steckelbroeck@hotmail.com
authors.forename: Stephan
authors.initials: S
authors.lastname: Steckelbroeck
authors.forename: Alexander
authors.initials: A
authors.lastname: Nassen
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ugele
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.forename: Matthias
authors.initials: M
authors.lastname: Watzka
authors.forename: Annette
authors.initials: A
authors.lastname: Reissinger
authors.forename: Hans
authors.initials: H
authors.lastname: Clusmann
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.forename: Lothar
authors.initials: L
authors.lastname: Siekmann
authors.forename: Dietrich
authors.initials: D
authors.lastname: Klingmüller
authors.forename: Volkmar H
authors.initials: VH
authors.lastname: Hans
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis*; D012737:Sex Factors; D043266:Steryl-Sulfatase / Q000235:genetics* / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism; D013702:Temporal Lobe / Q000201:enzymology*
chemical_list: D012333:RNA, Messenger; D019314:Dehydroepiandrosterone Sulfate; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; D043266:Steryl-Sulfatase