Expression of Steroid Receptor Coactivator-1 Was Regulated by Postnatal Development but Not Ovariectomy in the Hippocampus of Rats

Abstract

Female steroids such as estrogens and progestins, through their nuclear receptors, play important roles in regulation of the structure and function of the hippocampus. Steroid receptor coactivator-1 (SRC-1) has been detected in embryonic and/or adult hippocampus of rodents, and SRC-1 null mice showed significantly longer escape latency in the Morris maze test, indicating a role of this coactivator in the regulation of hippocampus function. Whether this is regulated by development and circulating ovary hormones remains unclear. In this study, postnatal development and ovariectomy for regulation of hippocampal SRC-1 in female rats were investigated by Western blot and immunohistochemistry. The results showed that SRC-1-immunopositive materials were predominantly detected in the CA1 pyramidal cell layer and dentate gyrus granular cell layer. Very low levels of SRC-1 were detected at postnatal day 0, but they increased with development. The highest levels of SRC-1 were detected at postnatal day 14, then they decreased to adult levels from postnatal day 30; significantly lower levels of SRC-1 were detected in the middle-aged (18-month-old) hippocampus when compared with that of the adult. Western blot and immunohistochemistry demonstrated that hippocampal SRC-1 expression was unchanged after ovariectomy, no significant differences were noticed from day 3 to 8 weeks postsurgery when compared with sham animals. The above results showed that hippocampal SRC-1 is regulated by postnatal development but not ovariectomy, and that the exact role of SRC-1 in the estradiol regulation of hippocampus needs further investigation.

Steroid receptor coactivator-1 mediates letrozole induced downregulation of postsynaptic protein PSD-95 in the hippocampus of adult female rats

“…We also found that SRC-1 is regulated by development in both sexes and by orchidectomy [28][29] but not ovariectomy in the hippocampus of rats [29]. Furthermore, orchidectomy and letrozole treatment induced decrease of brain SRC-1 in a similar manner [10,30].…”

“…The Western blot analysis of SRC-1 and PSD-95 was carried out according to our previous description [28,31]. Proteins of hippocampus of the rats or cultured cells were extracted using a Protein Extract Kit (P0027, Beyotime Biotech; Beijing, China) and the protein concentration was determined using a BCA Assay Kit (P0010, Beyotime Biotech).…”

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

“…For orchidectomy, the skin of the scrotum of the male adult mice was opened, the epididymis was cut and the testes were removed (Harooni et al,2008). Ovariectomy was carried out according to our previous report (Zhang et al,2011a), a small midline incision (∼1.0 cm) was made in the skin halfway between the middle of the back and the base of the tail, starting at the last rib. The skin was moved to one side, and a small incision was made through the peritoneal lining on each side.…”

“…Several studies have reported the expression of SRC‐1 mRNA and/or protein in the hippocampus of mice (Bian et al,2011; Nishihara et al,2003) or rats (Meijer et al,2000; Ogawa et al,2001; Zhang et al,2011a, b). Higher SRC‐1 expression in the male hippocampus was reported under physiological conditions in the rats (Bousios et al,2001) and mice (Bian et al,2011).…”

“…Higher SRC‐1 expression in the male hippocampus was reported under physiological conditions in the rats (Bousios et al,2001) and mice (Bian et al,2011). We recently reported that in the female rats, hippocampal SRC‐1 and PSD‐95 were only transiently downregulated by ovariectomy (Zhang et al,2010, 2011a), significant sex differences of SRC‐1 in the adult brain of male and female mice were reported with male‐dominance (Bian et al,2011). However, currently we are still not clear whether there is any difference about the regulation of SRC‐1 and synaptic proteins by circulating male‐ and‐female sex hormones.…”