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

Expression of 5α-reductase and aromatase in labial salivary glands. In healthy labial salivary glands, 5α-reductase staining was strong in the nuclei of the acinar cells, whereas it had a more diffuse localization in the ductal epithelial cells (A, arrow head). This partial nuclear localization of 5α-reductase is very evident with nuclear DAPI counterstain (A). In contrast, aromatase immunoreactivity was polarized in the acinar cells so that it was expressed strongly on apical and lateral cell membrane domains (C, arrowhead) but was barely seen in the basal cell membrane (C, arrow) (C). Insert in (C): In salivary ducts aromatase was often seen also on the basal aspects of the ductal epithelial cells. In labial salivary glands of patients with SS, 5α-reductase staining was mostly cytoplasmic (B, compared to A). For the expression of aromatase in SS salivary glands, a similar expression was found as in healthy controls (D, compared to C). (E) and (F): The negative staining controls with normal, non-immune goat IgG, used instead of and at the same concentration as the specific primary antibodies, confirm the specificity of the stainings. Objective magnification ×200 in all panels and ×400 in the insert.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4496140&req=5

fig06: Expression of 5α-reductase and aromatase in labial salivary glands. In healthy labial salivary glands, 5α-reductase staining was strong in the nuclei of the acinar cells, whereas it had a more diffuse localization in the ductal epithelial cells (A, arrow head). This partial nuclear localization of 5α-reductase is very evident with nuclear DAPI counterstain (A). In contrast, aromatase immunoreactivity was polarized in the acinar cells so that it was expressed strongly on apical and lateral cell membrane domains (C, arrowhead) but was barely seen in the basal cell membrane (C, arrow) (C). Insert in (C): In salivary ducts aromatase was often seen also on the basal aspects of the ductal epithelial cells. In labial salivary glands of patients with SS, 5α-reductase staining was mostly cytoplasmic (B, compared to A). For the expression of aromatase in SS salivary glands, a similar expression was found as in healthy controls (D, compared to C). (E) and (F): The negative staining controls with normal, non-immune goat IgG, used instead of and at the same concentration as the specific primary antibodies, confirm the specificity of the stainings. Objective magnification ×200 in all panels and ×400 in the insert.

Mentions: 5α-reductase was mainly located in the nuclei of the acinar cells so that cytoplasmic staining was relatively weak. This nuclear localization was clearly seen in nuclear DAPI counterstained sections (Fig. 6A), whereas its localization was more diffuse in the ductal cells (arrowhead). Aromatase showed a very intimate association with the apical (and apolateral) acinar cell plasma membrane; it was not found on the basal plasma membrane domains of the acinar cells (Fig. 6C). In contrast, in ductal cells it was located on both the apical and basal plasma membrane domains (insert in Fig. 6C). Aromatase was not found in the cell cytoplasm or in the nuclei of any of the acinar or ductal cells.


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)

Expression of 5α-reductase and aromatase in labial salivary glands. In healthy labial salivary glands, 5α-reductase staining was strong in the nuclei of the acinar cells, whereas it had a more diffuse localization in the ductal epithelial cells (A, arrow head). This partial nuclear localization of 5α-reductase is very evident with nuclear DAPI counterstain (A). In contrast, aromatase immunoreactivity was polarized in the acinar cells so that it was expressed strongly on apical and lateral cell membrane domains (C, arrowhead) but was barely seen in the basal cell membrane (C, arrow) (C). Insert in (C): In salivary ducts aromatase was often seen also on the basal aspects of the ductal epithelial cells. In labial salivary glands of patients with SS, 5α-reductase staining was mostly cytoplasmic (B, compared to A). For the expression of aromatase in SS salivary glands, a similar expression was found as in healthy controls (D, compared to C). (E) and (F): The negative staining controls with normal, non-immune goat IgG, used instead of and at the same concentration as the specific primary antibodies, confirm the specificity of the stainings. Objective magnification ×200 in all panels and ×400 in the insert.
© Copyright Policy
Related In: Results  -  Collection

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

fig06: Expression of 5α-reductase and aromatase in labial salivary glands. In healthy labial salivary glands, 5α-reductase staining was strong in the nuclei of the acinar cells, whereas it had a more diffuse localization in the ductal epithelial cells (A, arrow head). This partial nuclear localization of 5α-reductase is very evident with nuclear DAPI counterstain (A). In contrast, aromatase immunoreactivity was polarized in the acinar cells so that it was expressed strongly on apical and lateral cell membrane domains (C, arrowhead) but was barely seen in the basal cell membrane (C, arrow) (C). Insert in (C): In salivary ducts aromatase was often seen also on the basal aspects of the ductal epithelial cells. In labial salivary glands of patients with SS, 5α-reductase staining was mostly cytoplasmic (B, compared to A). For the expression of aromatase in SS salivary glands, a similar expression was found as in healthy controls (D, compared to C). (E) and (F): The negative staining controls with normal, non-immune goat IgG, used instead of and at the same concentration as the specific primary antibodies, confirm the specificity of the stainings. Objective magnification ×200 in all panels and ×400 in the insert.
Mentions: 5α-reductase was mainly located in the nuclei of the acinar cells so that cytoplasmic staining was relatively weak. This nuclear localization was clearly seen in nuclear DAPI counterstained sections (Fig. 6A), whereas its localization was more diffuse in the ductal cells (arrowhead). Aromatase showed a very intimate association with the apical (and apolateral) acinar cell plasma membrane; it was not found on the basal plasma membrane domains of the acinar cells (Fig. 6C). In contrast, in ductal cells it was located on both the apical and basal plasma membrane domains (insert in Fig. 6C). Aromatase was not found in the cell cytoplasm or in the nuclei of any of the acinar or ductal cells.

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