2001 Fiscal Year Final Research Report Summary
Studies on Mechanisms for Development of Adrenocortical Zonation
| Project/Area Number |
12470030
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Keio University |
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Principal Investigator |
TOTANI Keiko Keio University, School of Medicine, Research Associate, 医学部, 助手 (30124952)
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| Co-Investigator(Kenkyū-buntansha) |
MUKAI Kuniaki Keio University, School of Medicine, Research Associate, 医学部, 助手 (80229913)
MITANI Fumiko Keio University, School of Medicine, Associate Professor, 医学部, 専任講師 (60041852)
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| Project Period (FY) |
2000 – 2001
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| Keywords | adrena cortex / steroid hormone / cell differentiation / organogenesis / stem cell / 幹細胞 |
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| Research Abstract |
The adrenal cortex in mammals contains three concentric zones, the zona glomerulosa (zG), zona fasciculata (zF), and zona reticularis (zR). We have previously reported that a functionally undifferentiated cell zone is present between zG and zF in rats. Our data suggested that the cell zone contains stem cells which produce cells capable of differentiating into the zG or zF/zR cells. In 2000, to develop in vitro model systems for analyzing the differentiation processes, we attempted to establish adrenocortical cell lines at undifferentiated stages similar to that of the cells found between zG and zF. Cell lines with such properties were established from a primary culture of the adrenal cells from transgenic mice harboring a temperature sensitive mutant of SV40 large T antigen gene. A101 cells at an undifferentiated state were found to differentiate to the zF-like cells upon dibutyryl CAMP treatment at the non-permissive temperature. There is a possibility that undifferentiated cells in culture express molecules playing a role in differentiation of adrenocortical cells. Then, in 2001 we attempted to clone cDNAs encoding proteins which were expressed in the undifferentiated cells by using differential hybridization screening. One of CDNA clones isolated was found to presumably encode a new extracellular protein. In situ hybridization analysis showed that the mRNA was present in the zona glomerulosa cells. When the encoded protein was expressed in a zF-like cells by stable transfection of an expression vector, expression of Cyp11b-1 gene encoding the corticosterone-synthesizing enzyme was repressed. This suggests that the protein is able to regulate the zone-specific differentiation of adrenocortical cells.
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