Healthy human salivary glands contain a DHEA-sulphate processing intracrine machinery, which is deranged in primary Sjogren's syndrome
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Salivary glands express STS, SULT2B1, HSD3B1, AKR1C3, SRD5A1 and CYP19A1, and the activity of the encoded enzymes allows for the conversion of circulating DHEAS and DHEA to DHT and oestrogens.
“Salivary glands express STS, SULT2B1, HSD3B1, AKR1C3, SRD5A1 and CYP19A1 and the activity of the encoded enzymes allows for the conversion of circulating DHEAS and DHEA to DHT and oestrogens (Spaan et al., 2009).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Spaan et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Vitali, C., Bombardieri, S., Jonsson, R., Moutsopoulos, H. M., Alexander, E. L., Carsons, S. E., Daniels, T. E., Fox, P. C., Fox, R. I., Kassan, S. S., et al. (2002) · Annals of the Rheumatic Diseases · doi:10.1136/ard.61.6.554 · Cited by 5,285 · see citing works
Labrie, F. (1991) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(91)90116-a · Cited by 685 · see citing works
Vitali, C., Bombardieri, S., Moutsopoulos, H. Μ., Coll, J., Gerli, R., Hatron, P., Kater, L., Konttinen, Y. T., Manthorpe, R., Meyer, O., et al. (1996) · Annals of the Rheumatic Diseases · doi:10.1136/ard.55.2.116 · Cited by 454 · see citing works
Self-citationLabrie, F., Luu-The, V., Labrie, C., & Simard, J. (2001) · Frontiers in Neuroendocrinology · doi:10.1006/frne.2001.0216 · Cited by 366 · see citing works
Salivary proteomic and genomic biomarkers for primary Sjögren's syndrome
Hu, S., Wang, J., Meijer, J. M., Ieong, S., Xie, Y., Yu, T., Zhou, H. F., Henry, S., Vissink, A., Pijpe, J., et al. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22954 · Cited by 362 · see citing works
Possible underlying mechanisms of sexual dimorphism in the immune response, fact and hypothesis
Grossman, C. J. (1989) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(89)90088-5 · Cited by 341 · see citing works
Välimaa, H., Savolainen, S., Soukka, T., et al. (2004) · Journal of Endocrinology · doi:10.1677/joe.0.1800055 · Cited by 230 · see citing works
Bowman, S., Gh, I., Holmes, G., Hamburger, J., & Ainsworth, J. R. (2004) · Scandinavian Journal of Rheumatology · doi:10.1080/03009740310004676 · Cited by 215 · see citing works
Ryu, O. H., Atkinson, J. C., Hoehn, G., et al. (2006) · Lara D. Veeken · doi:10.1093/rheumatology/kei212 · Cited by 215 · see citing works
Androgens and Estrogens Modulate the Immune and Inflammatory Responses in Rheumatoid Arthritis
CUTOLO, M., SERIOLO, B., VILLAGGIO, B., PIZZORNI, C., CRAVIOTTO, C., & SULLI, A. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04210.x · Cited by 194 · see citing works
Pharmacologic Basis for the Enhanced Efficacy of Dutasteride against Prostatic Cancers
Xu, Y. J., Dalrymple, S. L., Becker, R. E., Denmeade, S. R., & Isaacs, J. T. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0184 · Cited by 102 · see citing works
Neuroendocrine–immune interactions in synovitis
Cutolo, M., Straub, R. H., & Bijlsma, J. W. J. (2007) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0601 · Cited by 92 · see citing works
Valtýsdóttir, S. T., Wide, L., & Hällgren, R. (2001) · PubMed · Cited by 88 · see citing works
Laine, M., Porola, P., Udby, L., Kjeldsen, L., Cowland, J. B., Borregaard, N., Hietanen, J. H. P., Ståhle, M., Pihakari, A., & Konttinen, Y. T. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22828 · Cited by 75 · see citing works
Self-citationDifferent subcellular localization of sulphotransferase 2B1b in human placenta and prostate
He, D., Meloche, C. A., DUMAS, N. A., Frost, A. R., & Falany, C. N. (2004) · Biochemical Journal · doi:10.1042/bj20031524 · Cited by 72 · see citing works
Porola, P., VIRKKI, L., PRZYBYLA, B. D., Laine, M., Patterson, T. A., Pihakari, A., & Konttinen, Y. T. (2008) · The Journal of Rheumatology · doi:10.3899/jrheum.080220 · Cited by 59 · see citing works
Self-citationOestrogens in rheumatic diseases: friend or foe?
Cutolo, M., Capellino, S., & Straub, R. H. (2008) · Lara D. Veeken · doi:10.1093/rheumatology/ken150 · Cited by 59 · see citing works
Community management of knee pain in older people: is knee pain the new back pain?
Underwood, M. R. (2003) · British journal of rheumatology · doi:10.1093/rheumatology/keg439 · Cited by 53 · see citing works
The Influence of Sex Steroids on Sjögren's Syndrome
Porola, P., Laine, M., VIRKKI, L., et al. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1422.045 · Cited by 48 · see citing works
Self-citationImmunohistopathology of Sjögren's syndrome
Konttinen, Y. T., Porola, P., Konttinen, L., et al. (2006) · Autoimmunity Reviews · doi:10.1016/j.autrev.2006.03.003 · Cited by 42 · see citing works
Self-citationSjögren's syndrome: viewpoint on pathogenesis
Konttinen, Y. T., & Käsnä-Ronkainen, L. (2002) · Scandinavian Journal of Rheumatology · doi:10.1080/030097402317474883 · Cited by 36 · see citing works
Self-citationLactoferrin in Sjögren's Syndrome
Konttinen, Y. T., Kulomaa, M. S., Malmström, M., et al. (1984) · Arthritis & Rheumatism · doi:10.1002/art.1780270416 · Cited by 36 · see citing works
Self-citationExpression and activity of dehydroepiandrosterone sulfotransferase in human gastric mucosa
Tashiro, A., Sasano, H., Nishikawa, T., et al. (2000) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(00)00020-0 · Cited by 25 · see citing works
Konttinen, Y. T., & Käsnä-Ronkainen, L. (2002) · PubMed · Cited by 24 · see citing works
Self-citationLam, K., Zhang, L., Yamada, K. M., et al. (2001) · Journal of Cellular Physiology · doi:10.1002/jcp.1142 · Cited by 20 · see citing works
Onodera, K., Sasano, H., Ichinohasama, R., & Ooya, K. (1998) · Pathology International · doi:10.1111/j.1440-1827.1998.tb03838.x · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Intracrine androgen biosynthesis, metabolism and action revisited
Schiffer, L., Arlt, W., & Storbeck, K.-H. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.08.016 · Cited by 217 · see citing works
“Numerous studies have shown that androgen levels are higher within breast tissue than in circulation and are generally higher in benign tissue than cancerous tissue, demonstrating the relevance of intracrinology in breast and its dysregulation in cancer (Stanczyk et al., 2015).”
- Authors
- Spaan, M., Porola, P., Laine, M., Rozman, B., Azuma, M., & Konttinen, Y. T.
- Affiliations
- Helsinki University Hospital (FI)
- University of Helsinki (FI)
- Tokushima University (JP)
- Corresponding author
- Konttinen, Yrjö T.
- ORCID
- Spaan, Michelle
- Venue
- Journal of Cellular and Molecular Medicine
- Publisher
- Wiley
- Published
- 2009-07
- Volume
- 13
- Issue
- 7
- Pages
- 1261-1270
- ISSN
- 1582-1838 (ISSN-L)
- 1582-4934
- PMC
- PMC4496140
- OpenAlex
- W1984489773
- Cited by
- 43
- References
- 26
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 3 · 2017: 3 · 2016: 7 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 6
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cellular and Molecular Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Finska Läkaresällskapet
- European Commission
- Kansainvälisen Liikkuvuuden ja Yhteistyön Keskus
- Suomen Hammaslääkäriseura Apollonia
- Orionin Tutkimussäätiö
- Topics
- Health Sciences › Medicine › Physiology › Salivary Gland Disorders and Functions
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
- Keywords
- Sjögren's syndrome, salivary glands, DHEA sulfate, 3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, 5α-reductase, aromatase, steroid sulphatase, sulfotransferase, androgen metabolism, dihydrotestosterone, estrogen, labial salivary glands
- MeSH terms
- Aromatase, Cell Communication, Health, Humans, RNA, Messenger, Salivary Glands, Sjogren's Syndrome, Staining and Labeling, 17-Hydroxysteroid Dehydrogenases, Sulfotransferases, Gene Expression Regulation, Enzymologic, Case-Control Studies, Dehydroepiandrosterone Sulfate, Steryl-Sulfatase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
