-
[show abstract]
[hide abstract]
ABSTRACT: Females and males are different in brain and behaviors. These differences are mediated by steroids and their nuclear receptors which require coactivators to regulate the transcription of target genes. Studies have shown that these coactivators are critical for modulating steroid hormone action in the brain. Steroid receptor coactivator-1 has been implied in the regulation of reproduction, stress, motor learning, and limited studies have reported the sex-specific difference of SRC-1 mRNA or protein expression in specific brain regions, but the expression and differences of SRC-1 immunoreactivities in adult female and male brain remain unclear. In this study we reported that in both sexes, high levels of SRC-1 immunoreactivities were detected in olfactory bulb, cerebral cortex, hippocampus, Purkinje cells, some limited diencephalon and brainstem nuclei. The immunopositive materials were predominantly detected in cell nucleus, but in some regions they were also detected in the processes or fiber-like structures. In most of the brain regions studied, males possessed significantly higher levels of SRC-1 immunoreactivities than that of females. Higher levels of SRC-1 were detected in some nuclei related to learning and memory, motor regulation and reproduction indicated its potential roles in neurodegeneration and sex-dependent behavior and structure; the region- and sex-specific localization of SRC-1 immunoreactivities in agreement with that of some steroid receptors, indicating this coactivator play important roles in these hormone-reactive regions and cell groups related to reproduction, learning and memory, integration of motor and sense.
Steroids 02/2011; 76(3):269-79. · 2.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Previous studies have shown that steroid receptor coactivator-1 (SRC-1) is involved in the regulation of Purkinje cell development and motor learning, neural stem cell differentiation and reproductive-related plasticity. It is widely distributed in the adult brain, but the aging-related changes in the brain remain unclear. In this study age-related alterations of SRC-1 expression in female brain were examined. The results showed that striking age-related decreases of SRC-1 were noticed in those regions related to central regulation of motor (substantia nigra, pontine nuclei, lateral reticular nucleus and Purkinje cells, etc.), learning and memory (olfactory bulb, hippocampus, Purkinje cells, etc.), and neural stem cell (olfactory, dentate gyrus, cerebral cortex, etc.). Surprisingly, although SRC-1 immunopositive materials were predominantly detected in the cell nuclei, they were also detected in the extra-nuclear components predominantly in these motor-regulation sub-regions. The above results showing age-related decrease of SRC-1 in specific motor, learning and memory nuclei suggested its potential roles in neurodegenerative disorders, which may be one of the underlying mechanisms of the vulnerability of the aged brain.
Brain research 01/2011; 1382:88-97. · 2.46 Impact Factor
-
[show abstract]
[hide abstract]
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.
Developmental Neuroscience 01/2011; 33(1):57-63. · 3.63 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Steroid receptor coactivator-3 (SRC-3) has been reported to be overexpressed in the development and progression of many tumor types. SRC-3 has been detected in several lung cancer cell lines, but its expression and clinical significance in non-small cell lung cancer (NSCLC) remain unclear. In this study, 48 NSCLC tissues were collected and tissue microarrays were performed. The expression of SRC-3 was examined using nickel-intensified IHC. The results showed that of these 48 cases, 18 (37.5%) exhibited high levels of SRC-3 immunoreactivity, 23 (47.9%) exhibited moderate levels of SRC-3 immunoreactivity, and 7 (14.6%) were negative; thus, the total frequency of SRC-3 overexpression was 85.4% (41/48). This SRC-3 overexpression frequency was similar to the overexpression frequency observed for squamous cell carcinoma and adenocarcinoma (82.1% vs 90%) and for metastasis and non-metastasis patients (84.6% vs 85.7%). Data analysis demonstrated a significantly higher overexpression frequency in male patients compared with that in female patients (88.6% vs 76.9%). However, female patients tended to have higher expression levels of SRC-3, as measured by immunoreactivity, than male patients. These results demonstrate a high frequency of SRC-3 overexpression in NSCLC with a gender difference, suggesting that there is a specific role for SRC-3 in the pathogenesis of NSCLC.
Journal of Histochemistry and Cytochemistry 12/2010; 58(12):1121-7. · 2.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Postsynaptic density protein-95 (PSD-95) is hypothesized to control the excitatory-to-inhibitory ratio and plays an important role in the regulation of hippocampal synaptic plasticity, synaptogenesis, and learning and memory. In this report, we used immunoblotting to study the effects of aging and ovariectomy (OVX) on the expression of PSD-95 in the hippocampus of female rats. The results indicated that postnatal expression of hippocampal PSD-95 correlated with the fluctuation of circulating female sex hormones such as estrogen. Neonatal PSD-95 level was very low, but dramatically increased within the first month. The highest expression of PSD-95 was detected at postnatal day 30 (P30) and significantly decreased by 18 months. In the adult hippocampus, OVX significantly decreased PSD-95 expression within the first week, but it had recovered to adult levels 2 weeks later. Taken together, we conclude that circulating ovarian hormones may play a crucial role in the regulation of excitatory synapses within the hippocampus. Depletion of ovarian hormones can transiently and dramatically decrease the level of excitatory synapses for a limited time.
Synapse 11/2010; 64(11):875-8. · 2.94 Impact Factor
