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PHYSIOLOGICAL ROLES OF INSULIN-LIKE GROWTH FACTOR I ON THE PROLIFERATION OF MOUSE PITUITARY CELLS

胰岛素样生长因子 I 对小鼠垂体细胞增殖的生理作用

基本信息

批准号：
06640866
负责人：
TAKAHASHI Sumio
金额：
$ 1.34万
依托单位：
OKAYAMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

The present study was aimed to calrify the physiological roles of insulin-like growth factor-I (IGF-I) in the mouse pituitary glands. In the mouse pituitary glands, IGF-I containing cells and cells expressing IGF-I type I receptor were studied by in situ hybridization and immunohistochemical methods. Somatotrophs contained IGF-I and IGF-I mRNA,indicating that IGF-I was synthesized in somatotrophs. IGF-I receptors were also detected in somatotrophs. IGF-I inhibited growth hormone (GH)-releasing hormone-induced GH release in a monolayr-cultured system, indicating that IGF-I directly acts at the somatotroph level. In the same culture system, IGF-I and insulin stimulated the proliferation of pituitary cells. Epidermal growth factor (EGF) also stimulated the proliferation. These growth factor-induced proliferation was inhibited by administration of genistein, tyrosine kinase inhibitor. Estrogen with insulin treatment stimulated the proliferation, suggesting that "cross-talk" of estrogen-associated mechanism and insulin-associated one. Thus, the pituitary growth was regulated by not only steroid hormone, but also pituitary-derived growth factors. Estrogen increased pituitary IGF-I mRNA level. Estrogen effect on the proliferation was inhibited by EGF-receptor blocker RG 13022. Therefore, these findings suggest that estrogen action is mediated by IGF-I and/or EGF.IGF-I and EGF play physiological roles in an autocrine or paracrine manner in the pituitary gland.

本研究旨在探讨胰岛素样生长因子-I(IGF-I)在小鼠脑垂体腺中的生理作用。用原位杂交和免疫组织化学方法研究了小鼠脑垂体中含有IGF-I的细胞和表达I型I型受体的细胞。生长激素细胞含有IGF-I和IGF-I mRNA，表明IGF-I是在生长激素细胞中合成的。生长激素细胞中也检测到IGF-I受体。在单层培养体系中，IGF-I抑制生长激素(GH)释放激素诱导的GH释放，表明IGF-I直接作用于生长激素水平。在相同的培养体系中，IGF-I和胰岛素均能刺激垂体细胞的增殖。表皮生长因子(EGF)也能刺激细胞增殖。酪氨酸激酶抑制剂金雀异黄素可抑制这些生长因子诱导的细胞增殖。雌激素与胰岛素联合治疗可刺激细胞增殖，提示雌激素相关机制与胰岛素相关机制“串扰”。因此，垂体腺的生长不仅受类固醇激素的调节，还受垂体源生长因子的调节。雌激素可增加垂体IGF-I的mRNA水平。雌激素对细胞增殖的影响可被表皮生长因子受体阻断剂RG 13022所抑制。因此，这些发现表明雌激素的作用是由IGF-I和/或EGF介导的。IGF-I和EGF在脑下垂体中以自分泌或旁分泌的方式发挥生理作用。