Reference : Prolactin Suppresses Glucocorticoid-Induced Thymocyte Apoptosis in Vivo
Scientific journals : Article
Life sciences : Anatomy (cytology, histology, embryology...) & physiology
http://hdl.handle.net/2268/177745
Prolactin Suppresses Glucocorticoid-Induced Thymocyte Apoptosis in Vivo
English
Krishnan, Nithya [University of Cincinnati (OH, USA) > College of Pharmacy > > >]
Thellin, Olivier mailto [University of Cincinnati (OH, USA) > Department of Molecular and Cellular Physiology > > >]
Buckley, Donna J. [University of Cincinnati (OH, USA) > College of Pharmacy > > >]
Horseman, Nelson D. [University of Cincinnati (OH, USA) > Department of Molecular and Cellular Physiology > > >]
Buckley, Arthur R. [University of Cincinnati (OH, USA) > College of Pharmacy > > >]
2003
Endocrinology
Endocrine Society
144
5
2102-2110
Yes (verified by ORBi)
International
0013-7227
1945-7170
Chevy Chase
MD
[en] The hypothesis that prolactin (PRL) functions as an immunomodulator was based on studies showing lymphocyte PRL receptors, and its effects on growth, differentiation, and apoptosis in lymphoid cells. However, studies of PRL (PRL-/-) and PRL receptor knockout mice indicated that PRL was not required for immune system development or function under basal conditions. Because PRL maintains survival in glucocorticoid (GC)-treated Nb2-T lymphocytes in vitro, and PRL and GCs are elevated during stress, we investigated whether PRL protected T cells in vivo from GC-induced apoptosis. Adrenalectomized mice [PRL -/-, undetectable PRL; pituitary grafted PRL-/- (PRL-/-Graft), elevated PRL; and PRL+/-, normal PRL] were treated with dexamethasone (DEX) or PBS. Thymocytes and splenocytes were isolated and annexin V labeling of phosphatidylserine, DNA fragmentation, and caspase-3 activation were assessed as indices of apoptosis. Total thymocytes and CD4+ and CD8+ T cells obtained from DEX-treated PRL-/- mice exhibited significantly increased annexin V binding. In contrast, binding was not altered by DEX in PRL-/-Graft thymocytes. In addition, DEX induced classic DNA fragmentation in PRL-/- thymocytes. Elevated serum PRL reduced this effect. Thymocytes from DEX-treated PRL-/- mice exhibited increased caspase-3 activation, which was inhibited in cells from PRL-/-Graft mice. Finally, elevated expression of X-linked inhibitor of apoptosis, XIAP, was observed in thymi from DEX-treated PRL -/-Graft mice. This is the first demonstration that elevated PRL antagonizes apoptosis in thymocytes exposed to GCs in vivo. These observations suggest that, under conditions of increased GCs, such as during stress, elevated PRL functions physiologically to maintain survival and function of T-lymphocytes.
University of Cincinnati (OH, USA), Department of Molecular and Cellular Physiology
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/177745
10.1210/en.2003-0053

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