PMID- 26607693 OWN - NLM STAT- MEDLINE DCOM- 20160505 LR - 20220408 IS - 1879-1220 (Electronic) IS - 0960-0760 (Linking) VI - 156 DP - 2016 Feb TI - Dose-dependent regulation of steroid receptor coactivator-1 and steroid receptors by testosterone propionate in the hippocampus of adult male mice. PG - 23-31 LID - S0960-0760(15)30138-2 [pii] LID - 10.1016/j.jsbmb.2015.11.012 [doi] AB - Androgens have been proposed to play important roles in the regulation of hippocampus function either directly, through the androgen receptor (AR), or indirectly, through estrogen receptors (ERs), after aromatization into estradiol. Steroid receptor coactivator-1 (SRC-1) is present in the hippocampus of several species, and its expression is regulated by development and aging, as well as by orchidectomy and aromatase inhibitor letrozole administration, while ovariectomy only transiently downregulated hippocampal SRC-1. However, whether the expression of hippocampal SRC-1 can be directly regulated by testosterone, the principal male sex hormone, remains unclear. In the present study, we investigated the expression of hippocampal SRC-1 after orchidectomy and testosterone treatment using immunohistochemistry and Western blot analysis. We found that while hippocampal SRC-1 was significantly downregulated by orchidectomy (ORX), its expression was rescued by treatment with testosterone in a dose-dependent manner. Furthermore, we noticed that the decreased expression of hippocampal AR, ERs and the synaptic proteins GluR-1 and PSD-95 induced by ORX was also rescued by testosterone treatment in a dose-dependent manner. However, we found that hippocampal membrane estrogen receptor GPR30 and dendritic spine marker spinophilin were not altered by ORX or testosterone treatment. Together, the above results provided the first direct evidence for the androgenic regulation on hippocampal SRC-1, indicating that SRC-1 may be a direct target of androgenic regulation on the hippocampus. Furthermore, because AR and ERs can be differentially regulated by testosterone, and the transcriptional activity requires the involvement of local SRC-1, and considering the complicated regulatory pathway of each individual receptor, the converged hub regulator SRC-1 of these nuclear receptor networks is worthy of further investigation. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Qiu, Linli AU - Qiu L AD - Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China; Department of Filed Nursing, School of Nursing, Third Military Medical University, Chongqing 400038, China. FAU - Zhao, Yangang AU - Zhao Y AD - Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China. FAU - Guo, Qiang AU - Guo Q AD - Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China. FAU - Zhang, Yuanyuan AU - Zhang Y AD - Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China. FAU - He, Li AU - He L AD - Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China; Department of Filed Nursing, School of Nursing, Third Military Medical University, Chongqing 400038, China. FAU - Li, Wei AU - Li W AD - Department of Filed Nursing, School of Nursing, Third Military Medical University, Chongqing 400038, China. Electronic address: weilee2020@163.com. FAU - Zhang, Jiqiang AU - Zhang J AD - Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China. Electronic address: zhangjqtmmu@yahoo.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151126 PL - England TA - J Steroid Biochem Mol Biol JT - The Journal of steroid biochemistry and molecular biology JID - 9015483 RN - 0 (Androgens) RN - 0 (Receptors, Androgen) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Steroid) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) RN - WI93Z9138A (Testosterone Propionate) SB - IM MH - Androgens/metabolism MH - Animals MH - Hippocampus/*metabolism/ultrastructure MH - Male MH - Mice, Inbred C57BL MH - Nuclear Receptor Coactivator 1/*metabolism MH - Orchiectomy MH - Receptors, Androgen/metabolism MH - Receptors, Estrogen/metabolism MH - Receptors, Steroid/*metabolism MH - Synapses/metabolism/ultrastructure MH - Testosterone Propionate/*metabolism OTO - NOTNLM OT - Androgens OT - Hippocampus OT - Steroid receptor OT - Steroid receptor coactivator-1 OT - Synaptic protein OT - Testosterone EDAT- 2015/11/27 06:00 MHDA- 2016/05/06 06:00 CRDT- 2015/11/27 06:00 PHST- 2015/08/18 00:00 [received] PHST- 2015/11/13 00:00 [revised] PHST- 2015/11/16 00:00 [accepted] PHST- 2015/11/27 06:00 [entrez] PHST- 2015/11/27 06:00 [pubmed] PHST- 2016/05/06 06:00 [medline] AID - S0960-0760(15)30138-2 [pii] AID - 10.1016/j.jsbmb.2015.11.012 [doi] PST - ppublish SO - J Steroid Biochem Mol Biol. 2016 Feb;156:23-31. doi: 10.1016/j.jsbmb.2015.11.012. Epub 2015 Nov 26.