MECHANISM OF CELL DIFFERENTIATION OF ENDOCRINE CELL, WITH SPECIAL REFERENCE TO THE SOMATOMAMMOTROPH IN ANTERIOR PITUITARY GLAND.

内分泌腺，如前腺，由分泌不同激素的腺体细胞混合而成。这些不同的腺体细胞被认为是从相同的干细胞分化而来的，但内分泌细胞分化的机制仍在讨论中。我们最近建立了大鼠浆细胞瘤细胞系(MTT法/S)。四甲基偶氮唑盐/S细胞株在正常生长条件下只产生生长激素。溴脱氧尿嘧啶核苷(BrdU)标记的细胞也可见GH染色，并且有丝分裂的细胞胞浆内可见GH免疫阳性分泌颗粒。这些特征表明，MTT/D细胞以GH分泌细胞的形式增殖。我们先前曾报道过，在胰岛素或胰岛素样生长因子的刺激下，四甲基偶氮唑盐/S细胞转分化为催乳素细胞。此外，还报道了MTT微血管内皮细胞转分化所需的雌激素刺激。加入EGF可显著加速这种转分化，使生长激素营养细胞同时含有催乳素和生长激素。为了揭示细胞增殖和细胞分化之间的关系，进行了BrdU标记实验。结果表明，胰岛素和EGF诱导的催乳素细胞对BrdU掺入有明显的抑制作用，提示生长激素细胞转分化后的催乳素细胞不增殖或仅表现为非常缓慢的增殖。一般来说，催乳素细胞被认为是脑下垂体腺中最活跃的增殖细胞。体外和体内结果之间的这种差异是非常重要的，因为它可能表明垂体前叶催乳素细胞增殖的调节机制未知。另一方面，这些细胞的分化可能由邻近的支持细胞通过细胞通讯来控制。垂体前叶的滤泡-星状细胞是最重要的分支。

The endocrine gland, such as an anterior gland consist from the mixed population of different hormone secreting glandular cells. These different glandular cells supposedly differentiated from same stem cell however, the mechanism of cell differentiation in endocrine cells still under discusson. We recently established cell line(MtT/S)from rat plaractinoma. The MtT/S cell line produces only growth hormone(GH)in normal growth medium. The MtT/S cells labeled with bromodeoxyuridine(BrdU)also show staining for GH.Furthermore, mitotic MtT/S cells contain GH immunopositive secretory granules in their cytoplasm. These features indicate that MtT/D cells proliferate as GH-secreting cells. We reported previouly that MtT/S cells transdifferentiate into prolactin cells upon stimulation with insulin or insulin-like growth factor. A requirement of estrogen priming for MtT/S cell transdifferentiation has also been reported. This transdifferentiation is considerably accelerated by addition of EGF, resulting in somatomammotrophs contain both prolactin and GH.In order to reveal the relationship between cell proliferation and cell differentiation, a BrdU labeling experiment was performed. the results indicated that prolactin cells which were induced by stimulation with insulin and EGF showed markedly suppressed BrdU incorporation, indicating that prolactin cells that have transdifferentiated from growth hormone cells are non-proliferate or show only very slow proliferation. In general, prolactin cells are known to be the most active proliferative cells in the pituitary gland. This discrepancy between in vitro and in vivo result is verly important, since it may indicate an unknown mechanism for the regulation of prolacrtin cell proliferation in the anterior pituitary gland. On the other hand these cell differentiation may be controlled by neighboring supportive cells through cell cell communication. The folliculo-stellate cells in the anterior pituitary gland is the most important cand