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Sex‐specific Effect of Androgen on SFSWAP Expression in the Developing Mouse Cortex and Hippocampus
Author(s) -
Ridder Aaron,
Lee YuanYu,
Tsai HoungWei
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.991.5
Subject(s) - testosterone propionate , hippocampus , endocrinology , medicine , testosterone (patch) , hippocampal formation , androgen , cerebral cortex , sexual dimorphism , cortex (anatomy) , hypothalamus , biology , neuroscience , hormone
The cortex and hippocampus both are important for the control of complex cognitive and social behaviors, and considerable evidence suggests that these functions are sexually dimorphic. However, neural mechanisms underlying these differences are still not well understood. We have previously used immunoblotting to detect splicing factor suppressor of white apricot (SFSWAP) protein at a molecular weight of 105 kDa in the developing mouse cortex/hippocampus. We then measured cortical/hippocampal SFSWAP levels in male and female mice collected on the day of birth (PN0), and 7 (PN7), and 14 (PN14), and 21 (PN21) days after birth and found higher SFSWAP expression in females than males at all ages except PN0. Since androgens masculinize the brain nuclei of the hypothalamus and amygdala underlying male‐specific behaviors, we thus hypothesized that sexually dimorphic SFSWAP expression in the cerebral cortex/hippocampus might be similarly regulated by testosterone. To test our hypothesis, we treated male and female pups with either vehicle (0.05 ml sesame oil) or testosterone propionate (TP, 0.1 mg dissolved in 0.05 ml sesame oil) daily for three days starting on PN21. Their cortex/hippocampus (n= 6 per group) was collected 3–5 h after the last injection, followed by protein extraction and immunoblotting for SFSWAP. While a trend of female‐biased SFSWAP upregulation was found in vehicle‐treated groups, our results showed that TP decreased SFSWAP levels in female pups (0.67 ± 0.07 vs. 1.00 ± 0.08, p<0.05), not males. The observation of pharmacological effects of testosterone on SFSWAP downregulation in females suggests that SFSWAP expression might be mediated directly by androgen receptor or indirectly by estrogen receptors after it is converted to estradiol locally by aromatase. Further, the sex‐specific androgenic regulation of SFSWAP expression in the cortex/hippocampus could be due to the sex chromosome complement and/or the organizational effect of perinatal steroids occurring around birth. Support or Funding Information This work was supported by National Institutes of Health Grant SC3‐GM102051.