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

Healthy human salivary glands contain a DHEA-sulphate processing intracrine machinery, which is deranged in primary Sjögren's syndrome.
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DOI:
10.1111/j.1582-4934.2009.00727.x
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发表时间:
2009-07
影响因子:
5.3
通讯作者:
Konttinen YT
Konttinen YT
中科院分区:
医学2区
文献类型:
--
作者:
Spaan M;Porola P;Laine M;Rozman B;Azuma M;Konttinen YT

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干燥综合征(SS)患者唾液中的脱氢表雄酮(DHEA)和雄激素生物标志物水平较低,但唾液中的雌激素水平较高。假设是健康的腺体含有DHEA-硫酸处理内分泌机制;局部雄激素/雌激素失衡表明SS中这是紊乱的。对健康对照和SS患者的唇唾液腺进行类固醇硫酸酯酶、磺基转移酶、3 β-和17 β-羟基类固醇脱氢酶(3 β-和17 β-HSD)、5 α-还原酶和芳香化酶的间接免疫荧光和定量实时PCR(qRT-PCR)。在控制腺泡类固醇硫酸酯酶和磺基转移酶免疫反应位于基底外侧细胞部分。3 β-和17 β-HSD沿基底细胞部分形成强的间断带。5 α-还原酶主要定位于腺泡细胞核,芳香化酶主要定位于顶端细胞膜。所有酶在导管中分布更广。SS患者的类固醇硫酸酯酶较弱且紊乱,3 β-和17 β-HSD失去了其严格的基底腺泡细胞定位,5 α-还原酶主要见于腺泡细胞的胞浆中,而芳香化酶在SS和对照组中显示相似的染色。qRT-PCR检测结果显示,唇腺中3 β-HSD的表达量最低,而唇腺中3 β-HSD的表达量最低。健康的小管腺泡上皮细胞含有完整的DHEA(硫酸盐)激素原加工内分泌机制。这些酶在健康的腺泡中具有有组织的结构,其对应于从循环中摄取DHEA、产生活性二氢睾酮(DHT)终产物的核位点和产生雌激素进入唾液以输出到导管和口腔上皮细胞。SS的特征是3 β-HSD水平低,这与HSD和5 α-还原酶亚细胞区室化受损一起可以解释SS中局部DHT和雄激素生物标志物水平低。
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, 3β- and 17β-hydroxysteroid dehydrogenases (3β- and 17β-HSD), 5α-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. 3β- and 17β-HSD formed strong, interrupted bands along the basal cell parts. 5α-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, 3β- and 17β-HSD had lost their strict basal acinar cell localization and 5α-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 3β-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 3β-HSD levels, which together with impaired subcellular compartmentalization of HSDs and 5α-reductase may explain the low local DHT and androgen biomarker levels in SS.
DOI: 10.1136/ard.55.2.116
发表时间: 1996-02-01
影响因子: 27.4
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发表时间: 2007-01-01
期刊: AUTOIMMUNITY, PT D
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DOI: 10.1111/j.1749-6632.2002.tb04210.x
发表时间: 2002-01-01
期刊: NEUROENDOCRINE IMMUNE BASIS OF THE RHEUMATIC DISEASES II, PROCEEDINGS
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