| Co-Investigator(Kenkyū-buntansha) |
SEO Hisao Nagoya Univ., Res.Inst.Environ.Med., Professor, 環境医学研究所, 教授 (40135380)
KAMBE Fukushi Nagoya Univ., Res.Inst.Environ.Med., Associate Professor, 環境医学研究所, 助教授 (00211871)
IMAI Tsuneo Nagoya Univ., Hosp., Lecturer, 医学部, 講師 (80252245)
服部 公彦 名古屋大学, 環境医学研究所, 助手 (90359745)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
We reported the reduced expression of hDiminuto/DHCR24 gene in the adrenocortical cells adjacent to the cortisol-producing adenoma, and that this was associated with the increased apoptosis of the cells. These results indicated that hDiminuto controls proliferation of adrenocortical cells by inhibiting apoptosis. On the other hand, it was reported that ACTH induces cydin-dependent kinase inhibitors, p27kip1 and p57kip2, and suppresses proliferation of adrenocortical cells. In this study, we investigated the effects of ACTH on expression of p27kip1, p57kip2, proliferating cell nuclear antigen (PCNA) and hDiminuto in the adrenal glands of rats treated with dexamethasone (Dex).
[Material and Methods] Mail Wistar rats were treated for 5 days with Dex to inhibit endogenous ACTH secretion. ACTH was then administered to the rats, and they were killed at 0, 12, 24, 48 and 72 hours after ACTH. The adrenals were examined by Western blot, Northern blot and immunohistochemical analysis.
[Results] De
… More
x treatment induced shrinkage of adrenals, where no PCNA-expressing cells were detected, but most of cells expressed p27Kip1. Subsequent ACTH treatment resulted in the marked suppression of p27Kip1 expression specifically in adrenocortical cells at 12 hours. At 48 hours, the p27Kip1 suppression still continued in the cortex, while the PCNA-expressing cells appeared mainly around zona glomerulosa (zG), and increased at 72 hours. At this time, the p27Kip1-expressing cells also appeared in zG. In contrast to p27Kip1, the expression of p57Kip2 was not detected in the Dex-treated adrenal. However, its expression was markedly induced by ACTH in zG at 48 and 72 hours. The hDiminuto expression in the cortex was decreased by Dex, and its expression was increased by ACTH.
[Conclusion] The results demonstrate that the primary site for mitogenic action of ACTH in rat adrenocortex is zG, and that ACTH modulates proliferation and differentiation of adrenocortical cells by regulating the expression of p27Kip1, p57Kip2 and hDiminuto in time- and site-specific manners. Less
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