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

在本研究中，生长激素（GH）诱导的糖皮质激素被成功地复制在体外，并使用这个在体外系统，GH诱导胎儿垂体的分子机制进行了分析。E18胎儿的垂体腺在体外孵育无血清MEM-α加或不加DEX（50 nM）。孵育24 h后，GHmRNA仅在DEX孵育的组织中积累，达到与对照E19胎相适应的水平。这表明DEX作用的主要部位是垂体，母体因素、胎盘或胎儿下丘脑的影响不是胎儿垂体开始产生GH的先决条件。当E17垂体与DEX孵育时，GHmRNA积累水平明显降低。这被认为是能够响应DEX的tha细胞的数量差异的结果。在孵育5或10 h后，GHmRNA的DEX诱导不明显，然而，如果DEX在24 h孵育的前10 h存在于培养基中，则在孵育期的剩余时间内，GH诱导不需要DEX的连续存在。蛋白质合成抑制剂放线菌酮或嘌呤霉素可完全抑制DEX对胎儿垂体GH的诱导作用，提示DEX诱导胎儿垂体GHmRNA的表达是由垂体分泌的未知因子介导的，可能激活GH基因的转录。

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.