|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1995 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1994 : ¥1,500,000 (Direct Cost : ¥1,500,000)
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.