Analysis of the developmental process of immature growth hormone cells in the rat fetus.

本研究成功地在体外复制了糖皮质激素诱导的生长激素(GH)，并利用该体外系统分析了GH在胎儿脑下垂体部诱导的分子机制。孵育24小时后，GHmRNA仅在地塞米松孵育的组织中积聚，达到与对照组E19胚胎相当的水平。这表明DEX作用的主要部位是脑下垂体，母体因素、胎盘或胎儿下丘脑的影响不是胎儿脑下垂体产生GH的先决条件。当E17脑垂体与地塞米松共同孵育时，GHmRNA的积聚水平明显降低。DEX对GHmRNA的诱导作用在孵育5h和10h后并不明显，但如果在孵育24小时的前10h内存在DEX，则在接下来的孵育期内不需要继续存在DEX来诱导GH。加入蛋白质合成的抑制剂放线菌素，可完全抑制DEX诱导的GH。这些结果提示，DEX诱导胎儿脑下垂体生长激素基因的表达是由未知的因子介导的，该因子是由DEX反应产生的，可能激活GH基因转录的。

In the present study, growth hormone (GH) induction by glucocorticoid was successfully reproduced in vitro, and using this in vitro system, the molecular mechanisms underlying the GH-induction in the fetal pituitary gland was analyzed.The pituitary glands of E18 fetuses were incubated in vitro in serum free MEM-alpha with or without an addition of DEX (50nM). After 24h incubation, GHmRNA was accumulated only in the tissue incubated with DEX to a compatible level to that of control E19 fetuses. This ihdicates that the primary site of the DEX action is the pituitary gland and the influences of maternal factors, placenta or fetal hypothalamus are not prerequisite with respect to the initiation of GH production in the fetal pituitary gland. When E17 pituitaries were incubated with DEX,a distinct reduction of the level of GHmRNA accumulation was noted. This is considered to be the consequence of the difference in the number of tha cells which are capable of responding DEX.DEX induction of GHmRNA was not evident after 5 or 10 h incubation, however, if DEX was present in the medium for first 10h of the 24h-incubation, the continuous presence of DEX was not required for GH induction for the rest of incubation period. An addition of the cycloheximide, or puromycin, inhibitors of protein synthesis, completely inhibited the GH induction by DEX.These results taken as a whole suggest that the induction of GHmRNA in the fetal pituitary gland by DEX is mediated by unknown factor which is produced in pituitary gland in response to DEX,and probably activates the GH gene transcription.