Reduction of insulin signalling pathway IRS‐1/IRS‐2/AKT/mTOR and decrease of epithelial cell proliferation in the prostate of glucocorticoid‐treated rats

International Journal of Experimental Pathology - Tập 93 Số 3 - Trang 188-195 - 2012
Marina Bitencourt Costa1, Natália Moretti Violato1, Sebastião Roberto Taboga2, Rejane M. Góes2, José Roberto Bosqueiro1
1Department of Physical Education, Faculty of Sciences, São Paulo State University-Unesp, Bauru, São Paulo, Brazil
2Department of Biology, Institute of Biosciences, Letters and Exact Sciences, São Paulo State University-Unesp, São José do Rio Preto, São Paulo, Brazil

Tóm tắt

SummaryPrevious studies by our research group using a model of insulin resistance induced by dexamethasone (DEX) showed that in the rat ventral prostate there was epithelial and smooth muscle cell atrophy and there were also alterations in fibroblasts. Proteins of the insulin signalling pathway are known to be very important for cell proliferation and development. Thus, we investigated the insulin signalling pathway and epithelial proliferation in the rat ventral prostate in this model and correlated the findings with expression of glucocorticoid (GR) and androgen (AR) receptors. Insulin resistance was induced in adult male Wistar rats by injection of DEX (1 mg/kg, ip for 5 consecutive days), whereas control (CTL) rats received saline. DEX treatment resulted in a significant decrease in body weight, but not in prostate weight. Reductions in insulin receptor 1 (IRS‐1) (CTL 1.11 ± 0.06; DEX 0.85 ± 0.03), IRS‐2 (CTL 0.95 ± 0.05; DEX 0.49 ± 0.04), AKT (CTL 0.98 ± 0.03; DEX 0.78 ± 0.02), mammalian target of rapamycin (mTOR; CTL 0.65 ± 0.08; DEX 0.22 ± 0.05), GR (CTL 1.30 ± 0.09; DEX 0.57 ± 0.10) and AR (CTL 1.83 ± 0.16; DEX 0.55 ± 0.08) protein levels were observed in the prostate of DEX‐treated rats. The expression of the IRα‐subunit, phosphoinositide 3‐kinase, p‐AKT, p70S6K, extracellular signal‐regulated kinase (ERK) and p‐ERK was not altered. The frequency of AR‐positive cells in the epithelium of the prostate decreased in the glucocorticoid‐treated group, and the intensity of the reaction for this receptor in the cell nuclei was lower in this group. Furthermore, the treatment with DEX reduced the frequency of proliferating cell nuclear antigen‐positive (PCNA) cells 30‐fold. This study suggests that the reduction in the insulin signalling pathway proteins IRS‐1/IRS‐2/AKT/mTOR in the prostate of DEX‐treated rats may be associated with the morphological alterations observed previously.

Từ khóa


Tài liệu tham khảo

10.1111/j.1365-2613.2009.00696.x

10.2337/diabetes.52.4.974

Burén J., 2002, Dexamethasone impairs insulin signalling and glucose transport by depletion of insulin receptor substrate‐1, phosphatidylinositol 3‐kinase and protein kinase B in primary cultured rat adipocytes, J. Endocrinol., 146, 419

10.1054/tice.2000.0123

10.1210/en.2003-0788

Cheatham B., 1995, Insulin action and the insulin signaling network, Endocr. Rev., 16, 117

10.1074/jbc.272.22.14087

10.1074/jbc.C100271200

10.1002/j.1939-4640.1992.tb00338.x

10.1016/S0955-0674(98)80149-X

10.1016/j.bbrc.2003.09.132

10.1158/1535-7163.MCT-07-2408

Jackson F.L., 1984, Altered responses to androgens in diabetic male rats, Diabetes, 33, 819, 10.2337/diab.33.9.819

10.1172/JCI5971

Kaarbo M., 2010, PI3K‐AKT‐mTOR pathway is dominant over androgen receptor signaling in prostate cancer cells, Cell Oncol., 32, 11

10.1146/annurev.me.36.020185.002241

10.1074/jbc.M503158200

10.1210/en.2010-0722

10.1016/S0012-1606(02)00031-3

10.2174/156800909787580999

10.1093/jnci/93.22.1739

10.1385/ENDO:8:2:193

10.1210/en.130.6.3703

10.1097/MPA.0b013e31815ba826

10.1152/ajpendo.90931.2008

10.1007/s00441-008-0581-0

10.1210/jcem-54-1-131

10.1385/ENDO:21:2:115

10.1210/jc.77.5.1180

10.1016/j.jvs.2007.03.001

10.1172/JCI116060

10.1172/JCI116803

10.1038/nrc1974

10.1016/0014-2999(96)00422-0

10.1111/j.1365-2605.2006.00682.x

10.1007/BF00257788

10.1016/S0022-5347(17)43042-4

10.1007/s00125-004-1662-6

10.1111/j.1365-2613.2011.00772.x

10.1002/pros.21041

10.1210/en.2007-1259

10.1002/bies.950190608

10.1038/emboj.2011.277

10.1016/j.urolonc.2008.03.021

Thông tin
Thông tin xuất bản

International Journal of Experimental Pathology

Tập 93 Số 3

188-195

Thông tin tác giả