Androgen receptor: a new player associated with apoptosis and proliferation of pancreatic beta-cell in type 1 diabetes mellitus.
Androgen receptor (AR) mediates a wide range of cellular processes, such as proliferation, differentiation and apoptosis. Here we sought to identify whether AR was located in pancreatic beta-cells and investigate its functions in type 1 diabetes induced by multiple low doses of streptozotocin. Double/triple immunofluorescence, Western blot and semi-quantitative RT-PCR were carried out to determine variances of AR expression in beta-cells and correlation between AR and apoptosis/proliferation of beta-cells with progress of diabetes. In addition, in vitro primary beta-cells from control mice were cultured for 3 days or 6 days with compound stimulation in order to further identify effect of AR on beta-cell apoptosis and proliferation. AR expression in beta-cells peaked in control and 1-day diabetic mice, gradually and significantly decreased, even disappeared in diabetic mice with progress of diabetes. TUNEL-positive beta-cells were concomitant with overexpression of AR, and Ki67-positive beta-cells showed extremely weak, even negative AR staining. In vitro, AR could mediate beta-cell apoptosis, and AR antagonist flutamide contributed to beta-cell proliferation. In conclusion, AR is abundantly expressed in pancreatic beta-cell cytoplasm of control mice. With progress of type 1 diabetes, decrement of AR expression in diabetic mice contributes to prohibit beta-cells from apoptosis, and is strongly associated with beta-cell proliferation.
Department of Anatomy and Histo-Embryology, Key Laboratory of Environment and Genes Related to Disease (Ministry of Education), Medical School of Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, 710061, China.
Ru-Jiang
RJ
Li
Shu-Dong
SD
Qiu
Hai-Xu
HX
Wang
Hong
H
Tian
Li-Rong
LR
Wang
Yong-Wei
YW
Huo
D000726:Androgen Antagonists / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005455:Fluorescent Antibody Technique; D005485:Flutamide / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D011944:Receptors, Androgen; D005485:Flutamide