{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:07:21Z","timestamp":1767139641426},"reference-count":43,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2012,10,15]]},"abstract":"<jats:p> Ovariectomy\/estrogen deficiency causes selective apoptosis of the serous epithelial cells of the submandibular glands (SMG) in female mice. Because such apoptosis does not occur in healthy, estrogen-deficient male mice, it was hypothesized that dihydrotestosterone (DHT) protects epithelial SMG cells against apoptosis. The antiapoptotic effect of DHT on human epithelial HSG cells exposed to tumor necrosis factor-\u03b1 and cycloheximide was studied. Correspondingly, the proapoptotic effect of androgen deficiency was studied in orchiectomized (ORX) androgen-knockout (ARKO) and wild-type (WT) mice. The health state of the SMG cells was studied with Alcian blue-periodic acid Schiff (AB-PAS) and amylase staining and transmission electron microscopy (TEM). The eventual protective antiapoptotic effect of dehydroepiandrosterone (DHEA) treatment was tested in this model. Apoptosis was assessed using immunohistochemisty of cleaved effector caspase-3 and its activator caspase-8 and the TUNEL assay. To test for the bioavailability, intracrine metabolism and sex steroid effects of DHEA, cystein-rich secretory protein-3 (CRISP-3), and leucine-isoleucine-valine transport system 1 (LIV-1) were used as androgen- and estrogen-regulated biomarkers, respectively. DHT protected HSG cells against induced apoptosis. In mice, androgen deficiency resulted in extensive activation of apoptotic caspase-8\/3 cascade in serous epithelial cells. However, in salivary glands, active caspases were not translocated to nuclei but secreted to salivary ducts in exosome-like particles, which are associated with weak AB-PAS and amylase staining of the androgen-deprived cells and reduced number of intracellular secretory granules. DHEA treatment suppressed induction of proapoptotic caspases and almost normalized mucins and amylase and ultramophology of the serous epithelial cells in WT ORX but not ARKO ORX mice. According to the CRISP-3 and LIV-1 markers, DHEA probably exerted its effects via intracrine conversion to DHT. <\/jats:p>","DOI":"10.1152\/ajpendo.00139.2012","type":"journal-article","created":{"date-parts":[[2012,8,22]],"date-time":"2012-08-22T02:05:58Z","timestamp":1345601158000},"page":"E1015-E1024","source":"Crossref","is-referenced-by-count":10,"title":["Exosomal secretion of death bullets: a new way of apoptotic escape?"],"prefix":"10.1152","volume":"303","author":[{"given":"Nina","family":"Trokovic","sequence":"first","affiliation":[{"name":"Department of Medicine, Helsinki University Hospital, Helsinki, Finland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raimo","family":"P\u00f6ll\u00e4nen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Helsinki University Hospital, Helsinki, Finland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauliina","family":"Porola","sequence":"additional","affiliation":[{"name":"Department of Medicine, Helsinki University Hospital, Helsinki, Finland;"},{"name":"Department of Anatomy, University of Helsinki, Helsinki, Finland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasily","family":"Stegaev","sequence":"additional","affiliation":[{"name":"Department of Medicine, Helsinki University Hospital, Helsinki, Finland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Udo","family":"Hetzel","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Helsinki, Helsinki, Finland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c5sa","family":"Tivesten","sequence":"additional","affiliation":[{"name":"Wallenberg Laboratory for Cardiovascular Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Engdahl","sequence":"additional","affiliation":[{"name":"The Sahlgrenska Academy, Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Carlsten","sequence":"additional","affiliation":[{"name":"The Sahlgrenska Academy, Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena","family":"Forsblad-d'Elia","sequence":"additional","affiliation":[{"name":"The Sahlgrenska Academy, Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan Bourghardt","family":"Fagman","sequence":"additional","affiliation":[{"name":"Wallenberg Laboratory for Cardiovascular Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Lagerquist","sequence":"additional","affiliation":[{"name":"The Sahlgrenska Academy, Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yrj\u00f6 T.","family":"Konttinen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Helsinki University Hospital, Helsinki, Finland;"},{"name":"Department of Anatomy, University of Helsinki, Helsinki, Finland;"},{"name":"Orton Orthopaedic Hospital of the ORTON Foundation, Helsinki, Finland; and"},{"name":"COXA Hospital for Joint Replacement, Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2008.10.016"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1807"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2217\/imt.10.18"},{"key":"B4","first-page":"197","volume-title":"The Theory and Practice of Histological Techniques","author":"Bancroft JD","year":"2002","edition":"5"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1177\/28.8.7003006"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(92)90236-I"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308114100"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1021\/pr800658c"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.1070270102"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1210\/endo.133.1.8319566"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.0440a.x"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/01.bor.0000135450.78047.78"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65111-5"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63505-5"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/41.3.338"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400538200"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/art.21005"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400113"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2006.03.003"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2152\/jmi.56.290"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(93)90136-A"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/art.22828"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06264"},{"key":"B24","first-page":"2259","volume":"34","author":"Laroche M","year":"2007","journal-title":"J Rheumatol"},{"key":"B24a","first-page":"1552","volume":"24","author":"Manganelli P","year":"1997","journal-title":"J Rheumatol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200103)44:3<693::AID-ANR119>3.0.CO;2-7"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1053\/berh.1999.0078"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2617"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914843107"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.080220"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2010.02342.x"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2108\/zsj.12.243"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1042\/bj3090831"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405099101"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307915100"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19810801)48:3<745::AID-CNCR2820480314>3.0.CO;2-7"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2009.00727.x"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5381.1312"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e3181fe535b"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.6.554"},{"key":"B41","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.archoralbio.2009.07.011","volume":"54","author":"Wang Y","year":"2009","journal-title":"Arch Oral Biol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.43.30651"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/BF02331407"}],"container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpendo.00139.2012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T16:01:01Z","timestamp":1567958461000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpendo.00139.2012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,15]]},"references-count":43,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2012,10,15]]}},"alternative-id":["10.1152\/ajpendo.00139.2012"],"URL":"https:\/\/doi.org\/10.1152\/ajpendo.00139.2012","relation":{},"ISSN":["0193-1849","1522-1555"],"issn-type":[{"value":"0193-1849","type":"print"},{"value":"1522-1555","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10,15]]}}}