Nesfatin-1/NUCB2 is known to take part in the control of the appetite and energy metabolism. Recently, many reports have shown nesfatin-1/NUCB2 expression and function in various organs. We previously demonstrated that nesfatin-1/NUCB2 expression level is higher in the pituitary gland compared to other organs and its expression is regulated by 17β-estradiol and progesterone secreted from the ovary. However, currently no data exist on the expression of nesfatin-1/NUCB2 and its regulation mechanism in the pituitary of male mouse. Therefore, we examined whether nesfatin-1/NUCB2 is expressed in the male mouse pituitary and if its expression is regulated by testosterone. As a result of PCR and western blotting, we found that a large amount of nesfatin-1/NUCB2 was expressed in the pituitary and hypothalamus. The NUCB2 mRNA expression level in the pituitary was decreased after castration, but not in the hypothalamus. In addition, its mRNA expression level in the pituitary was increased after testosterone treatment in the castrated mice, whereas, the expression level in the hypothalamus was significantly decreased after the treatment with testosterone. The in vitro experiment to elucidate the direct effect of testosterone on NUCB2 mRNA expression showed that NUCB2 mRNA expression was significantly decreased with testosterone in cultured hypothalamus tissue, but increased with testosterone in cultured pituitary gland. The present study demonstrated that nesfatin-1/NUCB2 was highly expressed in the male mouse pituitary and was regulated by testosterone. This data suggests that reproductive-endocrine regulation through hypothalamus-pituitary-testis axis may contribute to NUCB2 mRNA expression in the mouse hypothalamus and pituitary gland.
The process of spontaneous abortion involves a complex mechanism with various cytokines, growth factors, and hormones during the pregnancy. However, the mechanism underlying spontaneous abortion by pro- and anti-inflammatory cytokines in the serum during the pregnancy is not fully understood. Therefore, the purpose of this study was to examine the relationship between the serum levels of pro- and anti-inflammatory cytokines and spontaneous abortion using the CBA/j × DBA/2 mouse model. Serum levels of pro-inflammatory cytokines, such as IFN-γ, IL-1α and TNF-α were not increased in abortion model mice, but anti-inflammatory cytokines, such as IL-4, IL-13 and IL-1ra were decreased compared to normal pregnant mice. In addition, serum levels of chemokine, such as SDF-1, G-CSF, M-CSF, IL-16, KC and MCP-1 were decreased in abortion model mice compared to normal pregnant mice. However, the expression levels of nesfatin-1/NUCB2 mRNA and protein in the uteri of implantation sites were significantly higher in abortion model mice than normal pregnant mice. These results suggest that uterine nesfatin-1/NUCB2 expression may be down-regulated by inflammatory cytokines and chemokines in the serum of pregnant mice. Moreover, this study suggests the possibility that nesfatin-1/NUCB2 expressed in the implantation sites may be associated with the maintenance of pregnancy.
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