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

本研究旨在阐明胰岛素样生长因子-I（IGF-I）在小鼠垂体中的生理作用。用原位杂交和免疫组织化学方法研究了小鼠垂体含IGF-I细胞和表达IGF-I Ⅰ型受体的细胞。生长激素细胞含有IGF-I和IGF-ImRNA，表明IGF-I在生长激素细胞中合成。IGF-I受体也检测到生长激素细胞。在单层培养系统中，IGF-I抑制生长激素（GH）释放酶诱导的GH释放，表明IGF-I直接作用于促生长素水平。在同一培养体系中，IGF-I和胰岛素刺激垂体细胞增殖。表皮生长因子（EGF）也刺激增殖。这些生长因子诱导的增殖被酪氨酸激酶抑制剂金雀异黄素抑制。雌激素与胰岛素联合治疗刺激增殖，提示“串扰”的雌激素相关机制和胰岛素相关机制之一。因此，垂体的生长不仅受类固醇激素的调节，而且还受垂体源性生长因子的调节。雌激素增加垂体IGF-I mRNA水平。EGF受体阻断剂RG 13022可抑制雌激素对细胞增殖的作用。因此，这些研究结果表明，雌激素的作用是由IGF-I和/或EGF介导的。IGF-I和EGF在垂体中以自分泌或旁分泌的方式发挥生理作用。

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.