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6 "Proliferation"
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Coordination of Multiple Cellular Processes by NR5A1/Nr5a1
Ken-ichirou Morohashi, Miki Inoue, Takashi Baba
Endocrinol Metab. 2020;35(4):756-764.   Published online December 23, 2020
DOI: https://doi.org/10.3803/EnM.2020.402
  • 6,658 View
  • 174 Download
  • 13 Web of Science
  • 14 Crossref
AbstractAbstract PDFPubReader   ePub   
The agenesis of the gonads and adrenal gland in revealed by knockout mouse studies strongly suggested a crucial role for Nr5a1 (SF-1 or Ad4BP) in organ development. In relation to these striking phenotypes, NR5A1/Nr5a1 has the potential to reprogram cells to steroidogenic cells, endow pluripotency, and regulate cell proliferation. However, due to limited knowledge regarding NR5A1 target genes, the mechanism by which NR5A1/Nr5a1 regulates these fundamental processes has remained unknown. Recently, newlyestablished technologies have enabled the identification of NR5A1 target genes related to multiple metabolic processes, as well as the aforementioned biological processes. Considering that active cellular processes are expected to be accompanied by active metabolism, NR5A1 may act as a key factor for processes such as cell differentiation, proliferation, and survival by coordinating these processes with cellular metabolism. A complete and definite picture of the cellular processes coordinated by NR5A1/Nr5a1 could be depicted by accumulating evidence of the potential target genes through whole genome studies.

Citations

Citations to this article as recorded by  
  • Development of sexual dimorphism of skeletal muscles through the adrenal cortex, caused by androgen-induced global gene suppression
    Fumiya Takahashi, Takashi Baba, Antonius Christianto, Shogo Yanai, Hyeon-Cheol Lee-Okada, Keisuke Ishiwata, Kazuhiko Nakabayashi, Kenichiro Hata, Tomohiro Ishii, Tomonobu Hasegawa, Takehiko Yokomizo, Man Ho Choi, Ken-ichirou Morohashi
    Cell Reports.2024; 43(2): 113715.     CrossRef
  • A novel heterozygous SF1/NR5A1 gene variant causes 46,XY DSD-gonadal dysgenesis with hypergonadotropic hypogonadism without adrenal insufficiency
    Luis Ramos
    Genes & Diseases.2024; 11(4): 101160.     CrossRef
  • A conserved NR5A1-responsive enhancer regulates SRY in testis-determination
    Denis Houzelstein, Caroline Eozenou, Carlos F. Lagos, Maëva Elzaiat, Joelle Bignon-Topalovic, Inma Gonzalez, Vincent Laville, Laurène Schlick, Somboon Wankanit, Prochi Madon, Jyotsna Kirtane, Arundhati Athalye, Federica Buonocore, Stéphanie Bigou, Gerard
    Nature Communications.2024;[Epub]     CrossRef
  • Testicular differentiation in 46,XX DSD: an overview of genetic causes
    Maria Tereza Martins Ferrari, Elinaelma Suelane do Nascimento Silva, Mirian Yumie Nishi, Rafael Loch Batista, Berenice Bilharinho Mendonca, Sorahia Domenice
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Role of NR5A1 Gene Mutations in Disorders of Sex Development: Molecular and Clinical Features
    Giovanni Luppino, Malgorzata Wasniewska, Roberto Coco, Giorgia Pepe, Letteria Anna Morabito, Alessandra Li Pomi, Domenico Corica, Tommaso Aversa
    Current Issues in Molecular Biology.2024; 46(5): 4519.     CrossRef
  • In silico structural features of the CgNR5A: CgDAX complex and its role in regulating gene expression of CYP target genes in Crassostrea gigas
    Theo Cardozo Brascher, Leonardo de Bortoli, Guilherme Toledo-Silva, Flávia Lucena Zacchi, Guilherme Razzera
    Chemosphere.2024; 361: 142443.     CrossRef
  • Conditional disruption of Nr5a1 directed by Sox9-Cre impairs adrenal development
    Ayako Tagami, Yayoi Ikeda, Kyoko Ishizuka, Mamiko Maekawa
    Scientific Reports.2024;[Epub]     CrossRef
  • Worldwide cohort study of 46, XY differences/disorders of sex development genetic diagnoses: geographic and ethnic differences in variants
    Chen Jiali, Peng Huifang, Jiang Yuqing, Zeng Xiantao, Jiang Hongwei
    Frontiers in Genetics.2024;[Epub]     CrossRef
  • Subunit-Specific Developmental Roles of PI3K in SF1-Expressing Cells
    My Khanh Q. Huynh, Sang Hee Lyoo, Dong Joo Yang, Yun-Hee Choi, Ki Woo Kim
    Endocrinology and Metabolism.2024; 39(5): 793.     CrossRef
  • An extragenital cell population contributes to urethra closure during mouse penis development
    Ciro Maurizio Amato, Xin Xu, Humphrey Hung-Chang Yao
    Science Advances.2024;[Epub]     CrossRef
  • Nuclear Receptor Gene Variants Underlying Disorders/Differences of Sex Development through Abnormal Testicular Development
    Atsushi Hattori, Maki Fukami
    Biomolecules.2023; 13(4): 691.     CrossRef
  • Identification of a novel class of cortisol biosynthesis inhibitors and its implications in a therapeutic strategy for hypercortisolism
    Soo Hyun Kim, Gi Hoon Son, Joo Young Seok, Sung Kook Chun, Hwayoung Yun, Jaebong Jang, Young-Ger Suh, Kyungjin Kim, Jong-Wha Jung, Sooyoung Chung
    Life Sciences.2023; 325: 121744.     CrossRef
  • Induced pluripotent stem cell line generated from a patient with differences in sex development (DSD) and multiple genetic variants including a large deletion in NR5A1
    Aisha L. Siebert, Grace B. Schwartz, Hana Kubo, Monica M. Laronda
    Stem Cell Research.2023; 71: 103154.     CrossRef
  • Loss of NR5A1 in mouse Sertoli cells after sex determination changes cellular identity and induces cell death by anoikis
    Sirine Souali-Crespo, Diana Condrea, Nadège Vernet, Betty Féret, Muriel Klopfenstein, Erwan Grandgirard, Violaine Alunni, Marie Cerciat, Matthieu Jung, Chloé Mayere, Serge Nef, Manuel Mark, Frédéric Chalmel, Norbert B. Ghyselinck
    Development.2023;[Epub]     CrossRef
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Original Articles
Endocrine Research
Effects of Oxytocin on Cell Proliferation in a Corticotroph Adenoma Cell Line
Jung Soo Lim, Young Woo Eom, Eun Soo Lee, Hyeong Ju Kwon, Ja-Young Kwon, Junjeong Choi, Choon Hee Chung, Young Suk Jo, Eun Jig Lee
Endocrinol Metab. 2019;34(3):302-313.   Published online September 26, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.3.302
  • 6,721 View
  • 83 Download
  • 3 Web of Science
  • 2 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Oxytocin (OXT) has been reported to act as a growth regulator in various tumor cells. However, there is a paucity of data on the influence of OXT on cell proliferation of corticotroph adenomas. This study aimed to examine whether OXT affects cell growth in pituitary tumor cell lines (AtT20 and GH3 cells) with a focus on corticotroph adenoma cells.

Methods

Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were conducted with AtT20 cells to confirm the effects of OXT on hormonal activity; flow cytometry was used to assess changes in the cell cycle after OXT treatment. Moreover, the impact of OXT on proliferating cell nuclear antigen (PCNA), nuclear factor κB, and mitogen-activated protein kinase signaling pathway was analyzed by Western blot.

Results

OXT treatment of 50 nM changed the gene expression of OXT receptor and pro-opiomelanocortin within a short time. In addition, OXT significantly reduced adrenocorticotropic hormone secretion within 1 hour. S and G2/M populations of AtT20 cells treated with OXT for 24 hours were significantly decreased compared to the control. Furthermore, OXT treatment decreased the protein levels of PCNA and phosphorylated extracellular-signal-regulated kinase (P-ERK) in AtT20 cells.

Conclusion

Although the cytotoxic effect of OXT in AtT20 cells was not definite, OXT may blunt cell proliferation of corticotroph adenomas by altering the cell cycle or reducing PCNA and P-ERK levels. Further research is required to investigate the role of OXT as a potential therapeutic target in corticotroph adenomas.

Citations

Citations to this article as recorded by  
  • Increased proliferation and neuronal fate in prairie vole brain progenitor cells cultured in vitro: effects by social exposure and sexual dimorphism
    Daniela Ávila-González, Italo Romero-Morales, Lizette Caro, Alejandro Martínez-Juárez, Larry J. Young, Francisco Camacho-Barrios, Omar Martínez-Alarcón, Analía E. Castro, Raúl G. Paredes, Néstor F. Díaz, Wendy Portillo
    Biology of Sex Differences.2023;[Epub]     CrossRef
  • Anterior pituitary gland synthesises dopamine from l‐3,4‐dihydroxyphenylalanine (l‐dopa)
    Santiago Jordi Orrillo, Nataly de Dios, Antonela Sofía Asad, Fernanda De Fino, Mercedes Imsen, Ana Clara Romero, Sandra Zárate, Jimena Ferraris, Daniel Pisera
    Journal of Neuroendocrinology.2020;[Epub]     CrossRef
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The Effect of Oxidative Stress on the Proliferation and Differentiation of Human Bone Marrow Stromal Cell-Derived Osteoblasts.
Eun Sook Oh, Ki Hyun Baek, Won Young Lee, Ki Won Oh, Hye Soo Kim, Je Ho Han, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Moo Il Kang
J Korean Endocr Soc. 2006;21(3):222-232.   Published online June 1, 2006
DOI: https://doi.org/10.3803/jkes.2006.21.3.222
  • 2,317 View
  • 20 Download
  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
The objectives of our study were to assess the effects of oxidative stress on the proliferation, differentiation and apoptosis of human bone marrow stromal cell (BMSC)-derived osteoblasts and to explore pathways by which osteoblast cell apoptosis was induced. METHODS: Mononuclear cells including BMSCs were cultured to osteoblastic lineage. Different doses of hydrogen peroxide (H2O2) were added to the culture media. The colony forming units-fibroblastic (CFU-Fs) were stained with crystal violet and alkaline phosphatase (ALP). The MTT assay was done to see the effect of H2O2 on cell viability. The effect of H2O2 on osteocalcin gene expression was determined by RT-PCR. The matrix calcification measurement was performed. FACS analysis was performed to determine the osteoblasts apoptosis. Caspase-3, -8 and 9 activity assay and cytochrome c release were measured. RESULTS: The size and number of ALP (+) CFU-Fs were also decreased by H2O2 treatment. When compared with the control group, H2O2 significantly decreased the total number of cells of each culture well during MTT assay. H2O2 significantly diminished expression of osteocalcin mRNA. N-acetylcystein (NAC) blocked the diminution of cell viability and the inhibition of osteocalcin mRNA expression by H2O2. H2O2 reduced matrix calcification. FACS analysis revealed H2O2 increased percentage of apoptotic cells. Addition of H2O2 resulted in the increase of caspase-9 and -3 activity but not caspase-8, and release of cytochrome c to the cytosol. CONCLUSION: These data suggest that, in primary human BMSCs, oxidative stress inhibits proliferation of stromal cells and inhibits the differentiation to osteoblastic lineage. In addition, oxidative stress induces apoptosis of human BMSC-derived osteoblasts and this may be mediated by mitochondrial pathway of apoptotic signal.

Citations

Citations to this article as recorded by  
  • Antioxidaitve and Differentiation Effects of Artemisia capillaris T. Extract on Hydrogen Peroxide-induced Oxidative Damage of MC3T3-E1 Osteoblast Cells
    Jee-Eun Seo, Eun-Sun Hwang, Gun-Hee Kim
    Journal of the Korean Society of Food Science and Nutrition.2011; 40(11): 1532.     CrossRef
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Search for "Proximal Histidine" of Thyroperoxidase Using Site Directed Mutagenesis.
Won Bae Kim, Young Kee Shong
J Korean Endocr Soc. 2003;18(4):371-378.   Published online August 1, 2003
  • 1,048 View
  • 16 Download
AbstractAbstract PDF
BACKGROUND
Thyroperoxidase (TPO), a transmembrane heme containing glycoprotein, catalyzes iodide organification and thyroid hormone synthesis. It is a single peptide making a loop with more than one disulfide bond. The tertiary conformational structure is essential for its enzymatic activity and immunogenicity. The proximal histidine is thought to play a major role in enzymatic activity since it is linked to the iron center of the heme. The crystal structure of TPO has not yet been reported, but some have suggested histidine 407 be a putative proximal histidine based on comparison of a.a. sequence for TPO and that for myeloperoxidase. METHODS: The putative histidine 407 and nearby histidine 414 were mutated to arginine to verify their role as the proximal histidine. Using site directed mutagenesis of wild type, human TPO cDNA, mutants H407R and H414R were made. Mutant cDNAs were transiently transfected into COS-7 cells, and the TPO enzyme activities were measured by guaiacol assay. Four cysteine residues around the putative proximal histidines were mutated to serine and their enzymatic activities were measured to check if they were involved in the formation of intra-molecular disulfide bonds. RESULTS: TPO protein expression of H407R- and H414R- transfected cells was confirmed by Western blot, using Hashimoto's IgG as primary antibody. Both the mutants H407R and H414R showed significant peroxidase enzymatic activity, although lower than those of the wild type. None of the cysteine mutants, C375S, C389S, C598S, and C655S, were detected by Hashimoto's IgG ordisplayed any enzymatic activity. CONCLUSION: These data suggest that neither histidine 407 nor histidine 414 functions as the "proximal histidine" in human TPO. All the cysteine residues checked (375, 389, 598, 655) might be involved in the formation of disulfide bonds in TPO molecules, but this hypothesis could not be confirmed. A further search for the other putative histidine residues using the same strategy is needed to define the structure-function relationship in the human TPO molecule.
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The Effects of Aging on the Proliferation and Differentiation of Osteoblasts from Human Mesenchymal Stem Cells.
Ki Hyun Baek, Hyun Jung Tae, Ki Won Oh, Won Young Lee, Chung Kee Cho, Soon Yong Kwon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Choon Choo Kim
J Korean Endocr Soc. 2003;18(3):296-305.   Published online June 1, 2003
  • 1,534 View
  • 23 Download
AbstractAbstract PDF
BACKGROUND
Osteoblasts originate from osteoprogenitor cells in bone marrow stroma, termed mesenchymal stem cells (MSCs) or bone marrow stromal cells. Each MSC forms colonies (colony forming units-fibroblasts [CFU-Fs]) when cultured ex vivo. There are some reports about the age-related changes of the number and osteogenic potential of osteoprogenitor cells, but any relationship has not been clearly established in humans. In this study, we counted MSCs using CFU-Fs count and examined the proliferative capacity and differentiation potential of osteoprogenitor cells. Finally, we analyzed how these parameters varied with donor age. METHODS: Bone marrow was obtained from the iliac crest of young (n=6, 27.2+/-8.6 years old) and old (n=10, 57.4+/-6.7 years old) healthy donors. Mononuclear cells, including MSCs, were isolated and cultured in osteogenic medium. In primary culture, we compared the colony-forming efficiency of MSCs between the two groups and determined the matrix calcification. When primary culture showed near confluence, the cells were subcultured. Alkaline phosphatase activity, osteocalcinexpression by RT-PCR and proliferative potential by MTT assay were examined by the time course of secondary culture. RESULTS: At the 15th day of primary culture, the mean number of CFU-Fs was significantly higher in the younger donors (young: 148.3+/-28.9, old: 54.3+/-9.1, p=0.02) and the mean size of CFU-Fs was also larger in the younger donors than the older donors. However, matrix calcification was not different between the two groups (young: 103.6+/-50.6, old: 114.0+/-56.5, p=NS). In secondary culture, alkaline phosphatase activities were significantly lower in the older donors. The younger donors showed peak alkaline phosphatase activity at day 10, while the older donors didn't showed a remarkable peak (young: 935.5+/-115.0U/mg, old: 578.4+/-115.7U/mg, p<0.05). Total cell number as a proliferative index increased progressively during the secondary culture and a significantly greater cell number was noted in the younger donors. Osteocalcin expression was generally upregulated in the younger donors, but this was not statistically significant. CONCLUSION: Our study shows that the number of osteoprogenitor cells is decreased during aging and that the proliferative capacity and differentiation potential of osteoprogenitor cells seem to be reduced during aging.
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The Effects of Iodide on the Cellular Functions and Expression of Thyroid Autoantigens in Thyroid Cells.
Young Joo Park, Eun Shin Park, Tae Yong Kim, Hye Seung Jung, Hyeong Kyu Park, Do Joon Park, Won Bae Kim, Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho
J Korean Endocr Soc. 2002;17(1):69-78.   Published online February 1, 2002
  • 1,389 View
  • 17 Download
AbstractAbstract PDF
BACKGROUND
Iodide has been known to control the function and the growth of the thyroid gland, and to be used as a substrate of thyroid hormone. Moreover, it has been suggested that excessive iodide stimulates the thyroid autoimmune responses. To evaluate the effects of iodide on thyrocytes, we investigated cell function and proliferation, or thyroid autoantigen expression after administering iodide to rats or FRTL-5 cells. MEHTODS AND RESULTS: Ten-weeks-old Sprague-Dawley rats were sacrificed after 7 days of NaI treatment. The expressions of thyroid autoantigens were examined by northern blot analysis. Chronic administration of iodide resulted in no effect on TSH receptor (TSHR) and thyroperoxidase (TPO) mRNA expression, while it increased thyroglobulin (TG) and diminished sodium-iodide symporter (NIS) mRNA expression. FRTL-5 cells were also treated with various concentrations of NaI. The generation of cAMP or iodide uptake was decreased, and the cellular growth was also inhibited by iodide. However, the expressions of all thyroid autoantigens (TSHR, TG, TPO, MHC class I and class II) except NIS were unchanged for 72 hours after iodide administration. The expression of NIS was mildly increased after 24 hours. CONCLUSION: Iodide resulted in decreased cell proliferation and cellular function of cAMP generation and iodide uptake. Chronic administration of iodide increased TG and diminished NIS mRNA expression in vivo but not in vitro
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