Healthy human salivary glands contain a DHEA-sulphate processing intracrine machinery, which is deranged in primary Sjogren's syndrome

Sjogren'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, 3 beta- and 17 beta-hydroxysteroid dehydrogenases (3 beta- and 17 beta-HSD), 5 alpha-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. 3 beta- and 17 beta-HSD formed strong, interrupted bands along the basal cell parts. 5 alpha-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, 3 beta- and 17 beta-HSD had lost their strict basal acinar cell localization and 5 alpha-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 3 beta-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 3 beta-HSD levels, which together with impaired subcellular compartmentalization of HSDs and 5 alpha-reductase may explain the low local DHT and androgen biomarker levels in SS.