Uchiyama T, Kaji H, Abe H, Chihara K
Division of Metabolism and Nutrition, Kobe University School of Medicine, Japan.
Neuroendocrinology. 1994 May;59(5):441-50. doi: 10.1159/000126690.
Increased growth hormone-releasing factor messenger ribonucleic acid (GRF mRNA) and decreased somatostatin (SRIF) mRNA levels have been reported in the hypothalamus of hypophysectomized rats as well as of dwarf mice. In order to elucidate the effect of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis on hypothalamic GRF and SRIF synthesis, we measured levels of mRNA coding for GRF and SRIF and for pituitary GH in pubertal male rats treated for 3 weeks with antirat GRF gamma-globulin (GRF-ab), anti-SRIF gamma-globulin (SRIF-ab) or both. Immunoneutralization of circulating endogenous GRF resulted in a marked decrease in serum IGF-I and pituitary GH mRNA levels in Northern blot analysis, whereas it caused a significant increase in GRF mRNA levels in the arcuate nucleus as assessed by both Northern blot and in situ hybridization analysis. SRIF mRNA levels in the periventricular nucleus were slightly decreased by GRF-ab treatment when analyzed by in situ hybridization, but not significantly after Northern blot analysis. Immunoneutralization of circulating endogenous SRIF failed to affect mRNA levels of hypothalamic GRF and SRIF but caused a slight reduction in pituitary GH mRNA levels. Levels of mRNA coding for hypothalamic GRF and pituitary GH were also measured by Northern blot analysis in young male rats treated with rat GRF-ab for 2 weeks and replaced with rat GH or IGF-I for the second 1 week. Replacement with either rat GH or IGF-I suppressed the increased hypothalamic GRF mRNA levels. These data indicate that endogenous GRF is essential for normal synthesis of pituitary GH and that both GH and IGF-I negatively regulate the synthesis of hypothalamic GRF.
据报道，在垂体切除的大鼠以及侏儒小鼠的下丘脑内，生长激素释放因子信使核糖核酸（GRF mRNA）水平升高，而生长抑素（SRIF）mRNA水平降低。为了阐明生长激素-胰岛素样生长因子I（GH-IGF-I）轴对下丘脑GRF和SRIF合成的影响，我们在用抗大鼠GRFγ球蛋白（GRF-ab）、抗SRIFγ球蛋白（SRIF-ab）或两者处理3周的青春期雄性大鼠中，测量了编码GRF、SRIF以及垂体GH的mRNA水平。在Northern印迹分析中，循环内源性GRF的免疫中和导致血清IGF-I和垂体GH mRNA水平显著降低，而通过Northern印迹和原位杂交分析评估，它导致弓状核中GRF mRNA水平显著升高。通过原位杂交分析，GRF-ab处理使室周核中的SRIF mRNA水平略有降低，但在Northern印迹分析后无显著变化。循环内源性SRIF的免疫中和未能影响下丘脑GRF和SRIF的mRNA水平，但导致垂体GH mRNA水平略有降低。在用大鼠GRF-ab处理2周并在第二周用大鼠GH或IGF-I替代的年轻雄性大鼠中，也通过Northern印迹分析测量了编码下丘脑GRF和垂体GH的mRNA水平。用大鼠GH或IGF-I替代均可抑制下丘脑GRF mRNA水平的升高。这些数据表明，内源性GRF对于垂体GH的正常合成至关重要，并且GH和IGF-I均对下丘脑GRF的合成起负调节作用。
