Testosterone Regulates NUCB2 mRNA Expression in Male Mouse Hypothalamus and Pituitary Gland

선소정,전다운,김희정,Yiwa Chung,최나래,양현원 한국발생생물학회 2017 발생과 생식 Vol.21 No.1

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.

Tissue-Specific Localization NUCB2/nesfatin-1 in the Liver and Heart of Mouse Fetus

선소정,양현원 한국발생생물학회 2018 발생과 생식 Vol.22 No.4

NUCB2/nesfatin-1 is first known to be expressed in the hypothalamus while controlling appetite and energy metabolism. However, recent studies have shown that NUCB2/nesfatin-1 was expressed in the various or-gans as well as the hypothalamus. Our previous reports also demonstrated that NUCB2/nesfatin-1 was expressed in the ovary, testis, pituitary gland, lung, kidney, and stomach of fetal and adult mice. However, the role of NUCB2/nesfatin-1 in mouse fetus remains unknown. Thus, the aim of this study was to investigate whether NUCB2/nestatin-1 is expressed in mouse fetus at the developmental stage in which organogenesis begins. To do this, we performed in situ hybridization (ISH) and immunohistochemistry (IHC) staining to examine the distribu-tion of NUCB2 mRNA and nesfatin-1 protein in the mouse fetal organs during early developmental stages, espe-cially at embryonic day (E) 10.5. As a result of ISH, NUCB2 mRNA positive signals were more frequent in the liver, but there were relatively few positive signals in heart. On the other hand, no positive signals were detected in other organs. These ISH results were validated by IHC staining and qRT-PCR analysis. Expression of nesfatin-1 protein detected by IHC staining was similar to that of NUCB2 mRNA detected by ISH in the liver and heart. In addition, the levels of NUCB2 mRNA expression analyzed by qRT-PCR were significantly increased in the liver and heart compared to other organs of the mouse fetus at E13.5, whereas its level was extensively decreased in the liver, but increased in the lung, stomach, and kidney of the mouse fetus at E17.5. These results suggest that NUCB2/nesfatin-1 may play an important role in liver and heart development and physiological functions in the developmental process of mouse fetus. Further studies are needed on the function of NUCB2/nesfatin-1, which is highly expressed in the various organs, including liver and heart during mouse development.

일반대학 유지충원율에 영향을 미치는 요인 분석

설가인,선소정,박나경,정제영 한국교육행정학회 2022 敎育行政學硏究 Vol.40 No.3

This study considers the ratio of new entrants and enrolled students to the institutional entrance quota as an important indicator of the subsistence of universities. Furthermore, it examines the patterns of the academic and research environment and performances at high- to low-ranking universities for this ratio by analyzing trends in 2017-2020. Universities were classified into three categories of A (high), B (middle), and C (low) ranks according to their ratio of new entrants and enrolled students to the institutional entrance quota for 2021. A hierarchical multiple regression analysis was conducted using the mean value of rankings for each university in 2017-2019 to investigate the factors that affect the ratio of new entrants and enrolled students to the institutional entrance quota. According to university trends by ranking, while all variables did not show consistent patterns, there were more national/public universities and capital area universities in the A rank than in the B or C ranks, and the size of these universities tended to be larger than in the other two ranks. The analysis results for the factors affecting the ratio of new entrants and enrolled students to the institutional entrance quota show that national/public universities, universities in the capital area, and larger universities tend to have a positive effect on the ratio, and the impact of the variables of university characteristics was quite large. Conversely, the distinct influence of the variables of the academic and research environment was relatively small, but that of the variables of performance was relatively strong. This study verified that due to the great impacts of the variables of university characteristics that are determined since the institutions’ establishment and the variables of academic and research performance among universities with fixed rankings, the ratio of new entrants and enrolled students to the institutional entrance quota could act as another factor that solidifies the standing of universities. Therefore, this study suggests that policy efforts should be made to close the gap between these higher education institutions. 본 연구에서는 유지충원율을 대학 존속 여부를 가늠할 주요 지표로 간주하고, 유지충원율 상위~하위 대학이 교육·연구 여건 및 성과에서 어떤 양상을 보였는지 2017~2020년의 추이를 분석하였다. 이를 위해 2021년 기준 유지충원율에 따라 일반대학을 A(상), B(중), C(하)등급으로 구분하였고, 유지충원율에 영향을 미치는 요인을 밝히기 위해 2017~2019년 대학별 평균치를 활용하여 위계적 중다회귀분석을 실시하였다. 등급에 따른 대학의 추이를 살펴본 결과, 모든 변수가 동일한 패턴을 보이지 않았지만 A등급은 B, C등급에 비해 국·공립대학과 수도권 대학의 비중이 높았고, 대학의 규모가 큰 편이었다. 그리고 교사시설 확보율, 전임교원 확보율, 학생 1인당 교육비, 전임교원 1인당 연구비, 취업률, 전임교원 1인당 연구실적, 학생 1인당 재정지원사업 수혜액이 가장 높았고, 특히 전임교원 1인당 연구비 및 학생 1인당 재정지원사업 수혜액의 등급 간 격차가 매우 컸다. 한편, 유지충원율에 영향을 미치는 요인을 분석한 결과, 국·공립대학일수록, 수도권 대학일수록, 대학의 규모가 클수록 유지충원율에 정적인 영향을 미쳤고, 대학 특성 변수의 영향력이 상당하였다. 반면 교육·연구 여건 변수의 고유한 영향력은 상대적으로 작았고, 전임교원 확보율이 높을수록, 학생 1인당 교육비가 낮을수록 유지충원율에 정적인 영향을 미쳤다. 교육·연구 성과 변수의 경우, 취업률과 전임교원 1인당 연구실적이 높을수록, 학생 1인당 재정지원사업 수혜액이 많을수록 유지충원율에 정적인 영향을 미쳤고, 성과 변수의 고유한 영향력은 비교적 컸다. 본 연구를 통해 비수도권 소규모 사립대학일수록 학생 충원에 어려움을 겪고 있음이 실증되었다. 그리고 대학 설립 당시부터 고정된 대학 특성 변수와 이미 상·하위 대학 간 격차가 고착화 된 교육·연구 성과 변수의 영향력이 커 유지충원율 또한 대학 서열화를 더욱 공고히 하는 요소로 작용할 수 있음을 확인하였다. 이에 대학 간 격차를 완화하고, 고등교육 전반의 경쟁력을 강화해 나가려는 정책적 노력이 필요함을 강조하였다.

NUCB2/nesfatin-1 suppresses the acrosome reaction in sperm within the mouse epididymis

김수현,선소정,김민비,하진아,석은지,양현원 한국통합생물학회 2023 Animal cells and systems Vol.27 No.1

Nesfatin-1, a polypeptide hormone derived from the nucleobindin 2 (NUCB2) precursor protein, isknown to regulate appetite and energy metabolism. Recent studies have also shown that NUCB2/nesfatin-1 is expressed in the reproductive organs of mice. However, the expression and potentialrole of NUCB2/nesfatin-1 in the mouse epididymis remain unclear. Therefore, we investigated theexpression of NUCB2/nesfatin-1 in the mouse epididymis and its potential function. NUCB2/nesfatin-1 was detected in the epididymis by qRT-PCR and western blotting, and highexpression levels were observed in epididymal epithelial cells by immunohistochemical staining. Pregnant mare’s serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG)injections significantly increased NUCB2/nesfatin-1 expression in the epididymis. Aftercastration, NUCB2/nesfatin-1 expression in the epididymis decreased, but was significantlyincreased by testosterone injection. Nesfatin-1-binding sites were found in the middle piece oftesticular sperm, but were scarcely detected in the sperm head. By contrast, nesfatin-1 bindingsites were identified on the sperm head within the epididymis. Furthermore, nesfatin-1treatment inhibited the acrosome reaction in epididymal sperm. These results suggest that thenesfatin-1 protein produced in the epididymis binds to nesfatin-1 binding sites on the spermhead and plays a role in suppressing the acrosome reaction before ejaculation.

Serum Cytokine Levels are related to Nesfatin-1/NUCB2 Expression in the Implantation Sites of Spontaneous Abortion Model of CBA/j × DBA/2 Mice

Yiwa Chung,김희정,선소정,양현원 한국발생생물학회 2017 발생과 생식 Vol.21 No.1

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 antiinflammatory 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.

Red ginseng extract regulates differentiation of monocytes to macrophage and inflammatory signalings in human monocytes

강보빈,김채영,황지수,선소정,양현원,서형주,최현선 한국식품과학회 2019 Food Science and Biotechnology Vol.28 No.6

This study was aimed to investigate the effect ofred ginseng extract (RGE) on monocyte to macrophagedifferentiation and inflammatory signalings in THP-1human monocytes. In HPLC analysis, RGE containedsaponin level of 516 lg/mg (extract) with 14 ginsenosides. RGE effectively suppressed the monocyte-to-macrophagedifferentiation induced by phorbol 12-myristate 13-acetated(PMA) by inhibiting the THP-1 cell adhesion. Thisresult is evidenced by the down-regulation of cluster ofdifferentiation molecule b (CD11b) and CD36. RGE significantlyreduced translocation of nuclear factor kappalight-chain-enhancer of activated B cells (NF-jB) (78%),while cytosolic NF-jB was increased (53%), comparedwith LPS group. In addition, RGE significantly increasedthe protein abundance of nuclear factor (erythroid-derived2)-like 2 (Nrf2) and its target protein, hemoxygenase-1(HO-1), but, Kelch-like ECH-associated protein 1(KEAP1), a negative regulator of Nrf2, was greatlydecreased by RGE. Furthermore, RGE effectivelymediated the regulation of Nrf2 level in nucleus andcytoplasm of THP-1.

Estradiol and progesterone regulate NUCB2/nesfatin-1 expression and function in GH3 pituitary cells and THESC endometrial cells

하진아,신정우,석은지,김수현,선소정,양현원 한국통합생물학회 2023 Animal cells and systems Vol.27 No.1

Estradiol (E2) and progesterone (P4) are essential sex steroid hormones that play critical roles in thepituitary gland and uterus. Recently, nesfatin-1, a polypeptide hormone that regulates appetiteand energy homeostasis in the hypothalamus, was found to be expressed in the pituitary glandand uterus. In this study, we aimed to investigate the relationship between these two steroidhormones and the expression and function of nesfatin-1 in the pituitary gland and uterus usingGH3 cells, a lacto-somatotroph cell line, and THESC cells, an endometrial stromal cell line. First,we verified the presence of nesfatin-1 and nesfatin-1 binding sites in GH3 and THESC cells. E2increased the mRNA expression of NUCB2, the gene encoding the nesfatin-1 protein, in GH3cells, while P4 had no significant effect. In THESC cells, NUCB2 mRNA expression was decreasedby E2 but increased by P4. In addition, nesfatin-1 significantly increased growth hormone (GH)and prolactin (PRL) mRNA expression in GH3 cells, and E2 enhanced this effect. In THESC cells,nesfatin-1 significantly increased the mRNA expression of insulin-like growth factor bindingprotein 1 (IGFBP1) and PRL, which are decidualization marker genes, and P4 further enhancedthis effect. These results suggest that nesfatin-1 may act as a local regulator of GH and PRLproduction in the pituitary gland and decidualization in the uterus, modulating its effects inresponse to E2 and P4.