RENAL GROWTH-HORMONE RECEPTOR GENE-EXPRESSION - RELATIONSHIP TO RENAL INSULIN-LIKE GROWTH-FACTOR SYSTEM

RENAL GROWTH-HORMONE RECEPTOR GENE-EXPRESSION - RELATIONSHIP TO RENAL INSULIN-LIKE GROWTH-FACTOR SYSTEM
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DOI:
10.1210/en.131.6.3061
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发表时间:
1992-12-01
期刊:
影响因子:
4.8
通讯作者:
BONDY, CA
BONDY, CA
中科院分区:
医学2区
文献类型:
--
作者:
CHIN, E;ZHOU, J;BONDY, CA

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为了阐明直接生长激素作用于肾脏的潜在位点,我们采用原位杂交技术定位生长激素受体(GHR)基因在发育过程中和成年大鼠中的表达。为了阐明GH和胰岛素样生长因子-I(IGF-I)在调节肾功能中的潜在相互作用,我们比较了GHR信使RNA(mRNA)与IGF-I受体和IGF-I在大鼠肾脏中的解剖定位。低水平的GHR mRNA存在于出生前的肾脏和丰富的增加,直到出生后第40天。垂体切除导致肾GHR mRNA水平降低,GH治疗导致肾GHR mRNA水平升高。肾脏GHR mRNA在近端直小管中含量最丰富,在髓质粗升支(MTAL)中含量较少,在肾小球或髓质内未检测到。相反,IGF-I受体mRNA集中在肾小球、远端肾单位和集合系统。GHR和IGF-I受体mRNA的唯一会聚点是在MTAL中,IGF-I mRNA定位于此。GHR和IGF-I受体基因在肾脏中的表达分离表明,每种激素沿着肾单位具有不同的作用范围,GH直接作用于近端直小管,而IGF-I可能作用于肾小球、远端肾单位和集合管。MTAL是肾IGF-I合成的位点,GHR在MTAL中的表达支持GH对肾IGF-I合成有直接影响的观点。最后,它似乎在肾脏,在其他GH敏感组织,GH可以调节其受体水平。
In order to elucidate potential sites of direct GH action on the kidney, we used in situ hybridization to localize GH receptor (GHR) gene expression during the course of development and in the adult rat. In order to illuminate potential interactions between GH and insulin-like growth factor-I (IGF-I) in regulating renal function, we compared the anatomical localization of GHR messenger RNA (mRNA) with that for the IGF-I receptor and for IGF-I in the rat kidney. Low levels of GHR mRNA were present in the kidney from before birth and increased in abundance until postnatal day 40. Hypophysectomy resulted in a decrease and GH treatment resulted in an increase in renal GHR mRNA levels. Renal GHR mRNA was most abundant in the proximal straight tubule, with lesser levels present in the medullary thick ascending limb (MTAL), and it was not detected in the glomerulus or inner medulla. In contrast, IGF-I receptor mRNA was concentrated in the glomerulus, distal nephron, and collecting system. The only point of convergence for GHR and IGF-I receptor mRNAs was in the MTAL, where IGF-I mRNA was localized. This segregation of GHR and IGF-I receptor gene expression in the kidney suggests that each hormone has distinct spheres of action along the nephron, with GH acting directly on the proximal straight tubule, whereas IGF-I may act on the glomerulus, distal nephron, and collecting duct. GHR expression in the MTAL, which is the site of renal IGF-I synthesis, supports the view that GH has a direct effect on renal IGF-I synthesis. Finally, it appears that in the kidney, as in other GH-sensitive tissues, GH may regulate its receptor levels.