2001 Fiscal Year Final Research Report Summary
Studies on the uterus specific regulation of erythropoietin gene expression and the function of erythropoietin in the uterus
| Project/Area Number |
11460043
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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 |
応用微生物学・応用生物化学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAGAO Masaya KYOTO UNIVERSITY, GRADUATE SCHOOL OF BIOSTUDIES, PROFESSOR, 生命科学研究科, 教授 (10237498)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Ryuzo THE UNTVBRSITY OF SIGA PREFECTURE, LIFE STYLE STUDIES, PROFESSOR, 人間文化学部, 教授 (60077378)
MASUDA Seiji KYOTO UNIVERSITY, GRADUATE SCHOOL OF BIOSTUDIES ASSOSIATE PROFESSOR, 生命科学研究科, 助教授 (20260614)
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| Project Period (FY) |
1999 – 2001
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| Keywords | erythropoietin / estrogen / uterus / hypoxia / oviduct / epididymis / angiogenesis |
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| Research Abstract |
Erythropoietic stimulation has been believed to be the sole physiological function of erythropoietin (Epo). Recently, however, the central nervous system and female reproductive organs have been found to produce Epo. To elucidate how Epo expression is regulated in these tissues, ovariectomized mice were given estrogen (E_2) and/or exposed to hypoxia, and the temporal patterns of Epo mRNA levels were examined. E_2 transiently induced Epo mRNA in the uterus but not in the kidney and cerebrum. Interestingly, the uterine Epo mRNA was hypoxia inducible only in the presence of E_2. Epo mRNA level in the kidney and cerebrum were elevated markedly within 4 h after exposure to hypoxia. Although the elevated level of Epo mRNA in the kidney decreased markedly within 8 h despite continuous hypoxia, the high level in the cerebrum was sustained for 【greater than or equal】 24 h, indicating that down regulation operates in the kidney but not in the brain. Thus Epo expression appears to be regulated in a tissue-specific manner, endorsing the tissue-specific function of Epo.
In the next study, we examined other female reproductive organs in the mouse with respect to Epo mRNA expression and its stimuli (E_2 and hypoxia)-induced changes. Although Epo mRNA expression was seen in the ovary and oviduct, the E_2-induced stimulation of Epo mRNA was found only in the oviduct. The E_2-induced stimulation in the oviduct was transient and rapidly downregulated. Epo mRNA expression in the oviduct was hypoxia inducible, in both the presence and the absence of E2.
We found that Epo is also produced in the male reproductive organs. Cultured epididymis produces Epo. Expression of epididymal Epo mRNA was drastically increased in the course of sexual maturation. Expression of Epo mRNA by the interstitial cells between the ductus epididymidis was found by in situ hybridization technique.
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