Chin E, Zhou J, Bondy C A
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Endocrinology. 1992 Dec;131(6):3061-6. doi: 10.1210/endo.131.6.1446640.
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.
为了阐明生长激素(GH)对肾脏直接作用的潜在位点,我们采用原位杂交技术来定位发育过程中和成年大鼠体内生长激素受体(GHR)基因的表达。为了阐明GH与胰岛素样生长因子-I(IGF-I)在调节肾功能方面的潜在相互作用,我们比较了大鼠肾脏中GHR信使核糖核酸(mRNA)与IGF-I受体及IGF-I的解剖定位。出生前肾脏中就存在低水平的GHR mRNA,其丰度在出生后第40天之前不断增加。垂体切除导致肾脏GHR mRNA水平下降,而GH治疗则使其水平升高。肾脏GHR mRNA在近端直管中最为丰富,在髓袢升支粗段(MTAL)中的水平较低,在肾小球或肾内髓质中未检测到。相比之下,IGF-I受体mRNA集中在肾小球、远端肾单位和集合系统中。GHR和IGF-I受体mRNA的唯一交汇点在MTAL,IGF-I mRNA也定位于此。肾脏中GHR和IGF-I受体基因表达的这种分离表明,每种激素在肾单位上具有不同的作用范围,GH直接作用于近端直管,而IGF-I可能作用于肾小球、远端肾单位和集合管。MTAL是肾脏IGF-I合成的部位,其中GHR的表达支持了GH对肾脏IGF-I合成有直接作用的观点。最后,在肾脏中,与其他对GH敏感的组织一样,GH似乎可以调节其受体水平。