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2009 ; 13
(7
): 1261-70
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Healthy human salivary glands contain a DHEA-sulphate processing intracrine
machinery, which is deranged in primary Sjögren s syndrome
#MMPMID19298523
Spaan M
; Porola P
; Laine M
; Rozman B
; Azuma M
; Konttinen YT
J Cell Mol Med
2009[Jul]; 13
(7
): 1261-70
PMID19298523
show ga
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.