Nogami H, Tachibana T
Department of Anatomy, Jikei University School of Medicine, Tokyo, Japan.
Endocrinology. 1993 Feb;132(2):517-23. doi: 10.1210/endo.132.2.7678792.
The effects of dexamethasone (DEX) on the onset of GH expression in the fetal rat pituitary gland were studied. Pregnant rats received oral administration of DEX dissolved in drinking water (25 mg/liter) for 40 h before killing on days 16-19 of pregnancy. The number of immunoreactive GH cells in the control fetus on day 18 was very small, whereas it was remarkably increased by DEX to a compatible value obtained from control fetuses on day 19. The effect of DEX on the induction of immunoreactive GH cells was found to be less potent on day 17 and not evident on day 16. The population of GH cells on day 19 was doubled, and they stained more intensely by GH antiserum after DEX treatment. In situ hybridization revealed that there were many GH messenger RNA (mRNA)-positive cells in the pituitary gland of a DEX-treated fetus at day 18, whereas they were negligible in number in the age-matched control. Northern blot analysis revealed that DEX induced accumulation of small amounts of GH mRNA in the fetal pituitary gland on day 17, whereas it induced a marked elevation of GH mRNA level on day 18. Reducing the levels of endogenous glucocorticoids by the administration of metyrapone (0.5 mg/ml in drinking water) to the pregnant rats from day 17-19 resulted in the significant reduction in the number of GH cells at day 19. Short-term treatment of DEX (duplicate sc injections at 18 h and 6 h before killing) also induced immunoreactive GH cells on day-18 fetuses but not on day-17 fetuses. Immunoreactive GH cells appeared on day 17 only after quadruplicate injections of DEX during last 40 h, suggesting that there is a difference in fetal sensitivity to DEX between days 17 and 18. These results indicate that immunoreactive GH cells and GH mRNA are inducible by DEX at an earlier stage of the fetal life than they normally appear. It is suggested that glucocorticoids play an important role in the development of GH cells in the fetal pituitary gland in vivo.
研究了地塞米松（DEX）对胎鼠垂体中生长激素（GH）表达起始的影响。在妊娠第16 - 19天处死前，给孕鼠口服溶于饮用水中的DEX（25毫克/升），持续40小时。第18天对照胎儿中免疫反应性GH细胞数量很少，而DEX使其显著增加至第19天对照胎儿的相应水平。发现DEX对免疫反应性GH细胞诱导的作用在第17天较弱，在第16天不明显。第19天GH细胞数量翻倍，DEX处理后它们被GH抗血清染色更深。原位杂交显示，在第18天经DEX处理的胎儿垂体中有许多GH信使核糖核酸（mRNA）阳性细胞，而在年龄匹配的对照中数量可忽略不计。Northern印迹分析显示，DEX在第17天诱导胎儿垂体中少量GH mRNA积累，而在第18天诱导GH mRNA水平显著升高。从第17 - 19天给孕鼠饮用美替拉酮（0.5毫克/毫升溶于饮用水中）以降低内源性糖皮质激素水平，导致第19天GH细胞数量显著减少。DEX短期处理（在处死前18小时和6小时重复皮下注射）也在第18天胎儿中诱导出免疫反应性GH细胞，但在第17天胎儿中未诱导出。仅在最后40小时四次注射DEX后，免疫反应性GH细胞才在第17天出现，表明第17天和第18天胎儿对DEX的敏感性存在差异。这些结果表明，免疫反应性GH细胞和GH mRNA在胎儿生命的早期阶段比正常出现时间更早地可被DEX诱导。提示糖皮质激素在体内胎儿垂体中GH细胞的发育中起重要作用。
