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

Spaan M, Porola P, Laine M, Rozman B, Azuma M, Konttinen YT - J. Cell. Mol. Med. (2009)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine/invärtes medicin, Helsinki University Central Hospital, Helsinki, Finland.

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.

Show MeSH

Related in: MedlinePlus

Intracrine metabolism of the dehydroepiandrosterone sulphate (DHEA-S) pro-hormone to various sex steroids. DHEA-sulphate can be subjected to desulphation by steroid sulphatase, but the desulphated DHEA can again be resulphated by sulfotransferase. DHEA is further metabolized by the following key enzymes as shown in the figure: 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase (3β-HSD), 17β-HSD, 5α-reductase and/or aromatase.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4496140&req=5

fig01: Intracrine metabolism of the dehydroepiandrosterone sulphate (DHEA-S) pro-hormone to various sex steroids. DHEA-sulphate can be subjected to desulphation by steroid sulphatase, but the desulphated DHEA can again be resulphated by sulfotransferase. DHEA is further metabolized by the following key enzymes as shown in the figure: 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase (3β-HSD), 17β-HSD, 5α-reductase and/or aromatase.

Mentions: Primates are unique in having adrenals with a reticular zone that secretes large quantities of the precursor sex steroids DHEA and its sulphate. Precursor sex steroids can be tailor-made to various active sex steroids according to the local tissue needs. The role of DHEA metabolism in different models of autoimmune diseases cannot therefore be easily studied in lower species, such as rodents. Intracrine DHEA-sulphate metabolism into androgens and/or oestrogens, as known in female breast and uterus or male prostate, is shown in Fig. 1[14], but has not been studied in salivary glands except for two single enzymes [15, 16]. This Fig. 1 also lays the groundwork to our two-part working hypothesis. Based on the local oestrogen/androgen imbalance in SS and the differences in the serum and salivary sex steroid profiles in healthy controls and patients [4], it was suggested that (i) there is a local DHEA processing intracrine machinery in healthy human salivary glands and (ii) that this is deranged in SS.


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

Spaan M, Porola P, Laine M, Rozman B, Azuma M, Konttinen YT - J. Cell. Mol. Med. (2009)

Intracrine metabolism of the dehydroepiandrosterone sulphate (DHEA-S) pro-hormone to various sex steroids. DHEA-sulphate can be subjected to desulphation by steroid sulphatase, but the desulphated DHEA can again be resulphated by sulfotransferase. DHEA is further metabolized by the following key enzymes as shown in the figure: 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase (3β-HSD), 17β-HSD, 5α-reductase and/or aromatase.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4496140&req=5

fig01: Intracrine metabolism of the dehydroepiandrosterone sulphate (DHEA-S) pro-hormone to various sex steroids. DHEA-sulphate can be subjected to desulphation by steroid sulphatase, but the desulphated DHEA can again be resulphated by sulfotransferase. DHEA is further metabolized by the following key enzymes as shown in the figure: 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase (3β-HSD), 17β-HSD, 5α-reductase and/or aromatase.
Mentions: Primates are unique in having adrenals with a reticular zone that secretes large quantities of the precursor sex steroids DHEA and its sulphate. Precursor sex steroids can be tailor-made to various active sex steroids according to the local tissue needs. The role of DHEA metabolism in different models of autoimmune diseases cannot therefore be easily studied in lower species, such as rodents. Intracrine DHEA-sulphate metabolism into androgens and/or oestrogens, as known in female breast and uterus or male prostate, is shown in Fig. 1[14], but has not been studied in salivary glands except for two single enzymes [15, 16]. This Fig. 1 also lays the groundwork to our two-part working hypothesis. Based on the local oestrogen/androgen imbalance in SS and the differences in the serum and salivary sex steroid profiles in healthy controls and patients [4], it was suggested that (i) there is a local DHEA processing intracrine machinery in healthy human salivary glands and (ii) that this is deranged in SS.

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine/invärtes medicin, Helsinki University Central Hospital, Helsinki, Finland.

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.

Show MeSH
Related in: MedlinePlus