2003 Fiscal Year Final Research Report Summary
Molecular and cellular analysis of autocrine and paracrine functions of endometrial growth factors
| Project/Area Number |
13440247
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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 |
生物形態・構造
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
TAKAHASHI Sumio Okayama University, Faculty of Science, Professor, 理学部, 教授 (90144807)
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| Co-Investigator(Kenkyū-buntansha) |
OKUDA Kiyoshi Okayama University, Graduate School of Natural Science and Technology, Professor, 自然科学研究科, 教授 (40177168)
TAKEUCHI Sakae Okayama University, Faculty of Science, Associate professor, 理学部, 助教授 (20226989)
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| Project Period (FY) |
2001 – 2003
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| Keywords | endometrium / growth factor / estrogen / progestin / proliferation / differentiation / receptor |
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| Research Abstract |
The growth and functions of uterine endometrial cells are regulated by estrogen and progestins. The actions of these sex steroid hormones are thought to be mediated by growth factors and cytokines produced, within the endometrium. The present study was aimed to clarify molecular and cellular regulatory mechanism of gene expression of growth factors and cytokines in the mouse endometrium. Estradiol stimulated transcription of insulin-like growth factor I (IGF-I), epidermal growth factor (EGF), transforming growth factor a (TGF-α), and TGF-β2 genes, and decreased interleukin-18 (IL-18) mRNA level. Progesterone decreased TGF-β1 and TGF-β3 mRNA levels. Thus, the gene expression of all growth factors studied is regulated by estrogen or progestin. Our in vitro study revealed that IGF-I, EGF and TGF-α stimulated DNA replication of endometrial cells. The IGF-I action in terms of DNA replication was mediated by IGF-I type I receptors through MAPkinase and PI3kinase pathways. Combination of estr
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adiol and progesterone stimulated the DNA replication of endometrial stroma cells, and this stimulatory action of the sex steroids was reduced by an EGF-receptor inhibitor RG13022. This result indicates that the stimulatory action by combination of estradiol and progesterone is mediated through EGF receptor signaling using ligands of EGF family-growth factors. These growth factors regulate proliferation of endometroial cells under stimulatory stimuli of estrogen. Estradiol and TGF-α decreased estrogen receptorα mRNA level, suggesting negative feedback system of estrogen action at the estrogen receptor level. Matrix metaloproteinases (MMPs) are thought to be associated with the growth and remodeling of the endometrium. MMP3, MMP7 and MMP9 mRNA levels were analyzed in mouse endometrium. These MMP mRNA levels increased at estrus, in adult mice. In vitro study estradiol decreased MMP3 mRNA levels at 24 hours. The findings altogether suggest that growth factors, cytokines and MMPs are associated with the growth and functions of uterine endometrium. Less
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Research Products
(12 results)
