title: Healthy human salivary glands contain a DHEA-sulphate processing intracrine machinery, which is deranged in primary Sjögren's syndrome.
abstract: Sjögren's syndrome (SS) patients have low salivary dehydroepiandrosterone (DHEA) and androgen biomarker levels, but high salivary oestrogen levels. The hypothesis was that the healthy glands contain DHEA-sulphate processing intracrine machinery; the local androgen/oestrogen imbalance suggests that this is disarranged in SS. Indirect immunofluorescence and quantitative real-time PCR (qRT-PCR) of steroid sulphatase, sulfotransferase, 3beta- and 17beta-hydroxysteroid dehydrogenases (3beta- and 17beta-HSD), 5alpha-reductase and aromatase were performed for labial salivary glands of healthy controls and persons with SS. In control acini steroid sulphatase and sulfotransferase immunoreactivities were located in the basolateral cell parts. 3Beta- and 17beta-HSD formed strong, interrupted bands along the basal cell parts. 5alpha-reductase was mainly located in acinar cell nuclei and aromatase in the apical cell membrane. All enzymes were more widespread in ducts. In SS, steroid sulphatase was weak and deranged, 3beta- and 17beta-HSD had lost their strict basal acinar cell localization and 5alpha-reductase was mainly found in the cytoplasm of the acinar cells, whereas aromatase showed similar staining in SS and controls. qRT-PCR of labial salivary glands disclosed all corresponding enzyme mRNAs with the levels of 3beta-HSD in SS being the lowest. Healthy tubuloacinar epithelial cells contain complete intracrine machineries for DHEA(-sulphate) pro-hormone processing. These enzymes have in healthy acini an organized architecture, which corresponds with DHEA uptake from the circulation, nuclear site of production of the active dihydrotestosterone (DHT) end product and production of oestrogens into saliva for export to ductal and oral epithelial cells. SS is characterized by low 3beta-HSD levels, which together with impaired subcellular compartmentalization of HSDs and 5alpha-reductase may explain the low local DHT and androgen biomarker levels in SS.
authors.affiliation: Department of Medicine/invärtes medicin, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Michelle
authors.initials: M
authors.lastname: Spaan
authors.forename: Pauliina
authors.initials: P
authors.lastname: Porola
authors.forename: Mikael
authors.initials: M
authors.lastname: Laine
authors.forename: Blaz
authors.initials: B
authors.lastname: Rozman
authors.forename: Masayuki
authors.initials: M
authors.lastname: Azuma
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D002450:Cell Communication; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006262:Health; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000201:enzymology / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D013194:Staining and Labeling; D043266:Steryl-Sulfatase / Q000235:genetics / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D019314:Dehydroepiandrosterone Sulfate; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001141:Aromatase; D015238:Sulfotransferases; D043266:Steryl-Sulfatase