Gonadectomy differentially regulates steroid receptor coactivator-1 and synaptic proteins in the hippocampus of adult female and male C57BL/6 mice

Hippocampus is one of the most important structures that mediates learning and memory, cognition, and mental behaviors and profoundly regulated by sex hormones in a sex‐specific manner, but the mechanism of underlying sex differences regulation is still unclear. We have previously reported that in the male and female mice, steroid receptor coactivator‐1 (SRC‐1) and some key synaptic proteins share similar developmental profile in the hippocampus, but how circulating sex hormones affect hippocampal SRC‐1 as well as these synaptic proteins remain unclear. In this study, we examined how gonad sex hormones regulate hippocampal SRC‐1, synaptophysin, PSD‐95, and AMPA receptor subtype GluR1 by using immunohistochemistry and Western blot. The results showed that in the female mice, ovariectomy affected hippocampal SRC‐1 and GluR1 were only detected at 2 weeks post operation, then it recovered to sham level; synaptophysin was unaffected at any timepoint examined; significant decrease of PSD‐95 was only detected at 4 weeks post operation. However, in the male hippocampus, SRC‐1 and PSD‐95 were decreased from one week and lasted to 4 weeks after orchidectomy, GluR1 decreased from 2 weeks after orchidectomy, but synaptophysin remained unchanged as in the females. Correlation analysis showed the profiles of SRC‐1 were positively correlated with GluR1 of the females, PSD‐95 and GluR1 of the males, respectively. The above results suggested a distinct regulatory mode between female and male gonad hormones in the regulation of hippocampal SRC‐1 and synaptic proteins, which may be one of the mechanisms contributing to the dimorphism of hippocampus during development and ageing. Synapse, 2012. © 2012 Wiley Periodicals, Inc.