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生长激素释放因子的分子遗传学

Molecular genetics of growth hormone-releasing factors.

作者信息

Chihara K, Uchiyama T, Shakutsui S, Kaji H, Okimura Y, Abe H

机构信息

Department of Medicine, Kobe University School of Medicine, Japan.

出版信息

Horm Res. 1994;42(4-5):182-8. doi: 10.1159/000184191.

DOI:10.1159/000184191
PMID:7868071
Abstract

To elucidate the effects of GRF on GH synthesis and of the GH-IGF-I axis on hypothalamic GRF synthesis, we measured the mRNA levels of hypothalamic GRF and pituitary GH in pubertal male rats treated for 3 weeks with antirat GRF gamma-globulin (GRF-ab), antisomatostatin 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 significantly increased GRF mRNA levels in the arcuate nucleus in both Northern blot and in situ hybridization analysis. Immunoneutralization of circulating endogenous SRIF failed to affect GRF mRNA levels but caused a slight reduction in pituitary GH mRNA. Then, we examined the effect of systemic replacement with rat GH or IGF-I for 1 week on GRF mRNA levels in the hypothalamus of rats treated with GRF-ab for 2 weeks. Replacement with either rat GH or IGF-I significantly suppressed the increased hypothalamic GRF mRNA levels. These data indicate that endogenous GRF is essential in normal synthesis of pituitary GH and that both GH and IGF-I negatively regulate the synthesis of hypothalamic GRF.

摘要

为阐明生长激素释放因子(GRF)对生长激素(GH)合成的影响以及GH-胰岛素样生长因子-I(IGF-I)轴对下丘脑GRF合成的影响,我们检测了用抗大鼠GRFγ球蛋白(GRF-ab)、抗生长抑素γ球蛋白(SRIF-ab)或两者处理3周的青春期雄性大鼠下丘脑GRF和垂体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,而在Northern印迹和原位杂交分析中,它显著增加了弓状核中的GRF mRNA水平。循环内源性SRIF的免疫中和未能影响GRF mRNA水平,但导致垂体GH mRNA略有降低。然后,我们检测了用GRF-ab处理2周的大鼠,给予大鼠GH或IGF-I全身替代1周对下丘脑GRF mRNA水平的影响。用大鼠GH或IGF-I替代均显著抑制了下丘脑GRF mRNA水平的升高。这些数据表明内源性GRF对垂体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。

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