Nogami H, Inoue K, Kawamura K
Department of Anatomy, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Endocrinology. 1997 May;138(5):1810-5. doi: 10.1210/endo.138.5.5124.
The mechanism by which glucocorticoids induce GH expression between embryonic days 18 and 19 (E18-19) in the fetal rat pituitary gland was examined with an in vitro organ culture system. Twenty-four hour incubation of E18 pituitary glands in serum-free medium containing either dexamethasone (DEX, 5-50 nM) or corticosterone (0.55 microM) resulted in a conspicuous accumulation of GH messenger RNA (mRNA), whereas no spontaneous expression of GH mRNA was noted without glucocorticoid. Triiodothyronine (1 nM) alone weakly induced GH mRNA but increased the effect of DEX 2-fold. The GH mRNA accumulation was not observed after 5 or 10 h incubation with DEX. However, a 10-h incubation with DEX followed by 14 h chase incubation without DEX resulted in apparent induction of GH mRNA. The induction of GH mRNA by DEX was completely inhibited by puromycin. These data, taken as a whole, suggest that the induction of GH mRNA by DEX in the fetal pituitary gland is not a direct effect of DEX on the GH gene but is mediated by a factor that is synthesized in the pituitary gland in response to DEX. Both immunoblot and RNase protection assays suggested that this factor is not pit-1, which is known to be required for GH mRNA expression.
采用体外器官培养系统研究了糖皮质激素在胚胎第18至19天(E18 - 19)诱导胎鼠垂体生长激素(GH)表达的机制。将E18垂体在含有地塞米松(DEX,5 - 50 nM)或皮质酮(0.55 microM)的无血清培养基中孵育24小时,导致GH信使核糖核酸(mRNA)明显积累,而在无糖皮质激素的情况下未观察到GH mRNA的自发表达。单独使用三碘甲状腺原氨酸(1 nM)对GH mRNA的诱导作用较弱,但可使DEX的作用增强2倍。与DEX孵育5或10小时后未观察到GH mRNA积累。然而,先与DEX孵育10小时,然后在无DEX的情况下进行14小时追踪孵育,导致明显诱导GH mRNA。嘌呤霉素完全抑制了DEX对GH mRNA的诱导作用。综合这些数据表明,DEX在胎垂体中对GH mRNA的诱导不是DEX对GH基因的直接作用,而是由垂体中响应DEX合成的一种因子介导的。免疫印迹和核糖核酸酶保护试验均表明该因子不是已知的GH mRNA表达所需的pit - 1。