{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:26:40Z","timestamp":1791163600043,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2007,7,30]],"date-time":"2007-07-30T00:00:00Z","timestamp":1185753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Sj\u00f6gren's syndrome (SS), an autoimmune disease of exocrine glands, typically starts at the time of adrenopause. We undertook this study to test the hypothesis that SS is characterized by an insufficient androgen effect at the target tissue level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched for androgen response elements (AREs) in the cysteine\u2010rich secretory protein 3 (<jats:italic>crisp\u20103<\/jats:italic>) gene. Dehydroepiandrosterone (DHEA) responsiveness was experimentally studied using quantitative reverse transcriptase\u2013polymerase chain reaction and immunofluorescence staining of human submandibular gland\u2013derived acinar cells and labial salivary gland explants with or without DHEA. Finally, glandular and salivary CRISP\u20103 in healthy controls and SS patients was analyzed using immunohistochemistry, in situ hybridization, and enzyme\u2010linked immunosorbent assay. Serum DHEA sulfate (DHEAS) and salivary DHEA levels were measured using a radioimmunometric method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Literature analysis and a search for AREs in gene banks suggested androgen dependency of human CRISP\u20103, and this was verified by studies of human submandibular gland acinar cells cultured with or without DHEA, in which DHEA increased CRISP\u20103 messenger RNA (mRNA) levels (<jats:italic>P<\/jats:italic> = 0.018). This finding was confirmed by the results of DHEA stimulation of labial salivary gland explants. Glandular CRISP\u20103 mRNA and protein labeling was weak and diffuse, coupled with low secretion in saliva (mean \u00b1 SEM 21.1 \u00b1 2.7 \u03bcg CRISP\u20103\/15 minutes in SS patients versus 97.6 \u00b1 12.0 \u03bcg CRISP\u20103\/15 minutes in healthy controls; <jats:italic>P<\/jats:italic> &lt; 0.0001). Compared with healthy controls, SS patients had low serum levels of DHEAS (<jats:italic>P<\/jats:italic> = 0.008) and also low salivary levels of DHEA (mean \u00b1 SEM 224 \u00b1 33 pmoles versus 419 \u00b1 98 pmoles; <jats:italic>P<\/jats:italic> = 0.005).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CRISP\u20103 pathology was seen in acini remote from lymphocyte foci and is apparently not secondary to local inflammation, but may represent some systemic effect in SS. Indeed, androgen deprivation in the salivary glands of SS patients is evidenced both by low salivary levels of DHEA and by low levels of DHEA\u2010regulated CRISP\u20103. This may explain some of the characteristic features of SS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22828","type":"journal-article","created":{"date-parts":[[2007,7,30]],"date-time":"2007-07-30T16:17:35Z","timestamp":1185812255000},"page":"2575-2584","source":"Crossref","is-referenced-by-count":60,"title":["Low salivary dehydroepiandrosterone and androgen\u2010regulated cysteine\u2010rich secretory protein 3 levels in Sj\u00f6gren's syndrome"],"prefix":"10.1002","volume":"56","author":[{"given":"Mikael","family":"Laine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauliina","family":"Porola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lene","family":"Udby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Kjeldsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack 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