Chen N Y, Chen W Y, Kopchick J J
Department of Clinical Research, Ohio University College of Osteopathic Medicine, Athens 45701, USA.
Endocrinology. 1997 May;138(5):1988-94. doi: 10.1210/endo.138.5.5123.
Elevated GH levels are frequently seen in poorly controlled type I diabetics and have been implicated in diabetic complications. Studies of GH and GH antagonist (GHA) transgenic mice with streptozotocin (STZ)-induced diabetes have revealed that GH has a permissive effect for diabetic nephropathy, and that expression of a GHA gene protected mice against diabetic kidney lesions. To investigate whether kidney GH receptor (GHR) and/or GH-binding protein may play a role in diabetic nephropathy, we evaluated GH-specific binding and messenger RNA levels for GHR/GH-binding protein in mouse livers and kidneys from bovine (b) GH or bGHA transgenic (Tg) mice and their nontransgenic (NTg) littermates with or without STZ-induced diabetes. We found that liver-specific GH binding is significantly higher in both bGH- and bGHA-Tg mice compared to that in their NTg controls. In contrast, kidney GH binding is significantly lower in bGH-Tg mice compared to that in NTg littermates. These results indicate that regulation of mouse GHR expression is tissue specific. STZ-induced diabetes decreased GH-specific binding in both liver and kidney of NTg and GHA-Tg mice, but not in bGH-Tg mice. The lowered GHR binding in diabetic NTg and GHA-Tg mice suggests the involvement of insulin in the regulation of GHR expression. The down-regulation of kidney GHR in GHA-Tg mice in combination with the presence of GHA may partially explain the protective mechanism of GHA against diabetic kidney lesions.
在控制不佳的I型糖尿病患者中，经常可以看到生长激素（GH）水平升高，并且其与糖尿病并发症有关。对链脲佐菌素（STZ）诱导糖尿病的GH和GH拮抗剂（GHA）转基因小鼠的研究表明，GH对糖尿病肾病具有促进作用，并且GHA基因的表达可保护小鼠免受糖尿病肾脏病变的影响。为了研究肾脏生长激素受体（GHR）和/或GH结合蛋白是否可能在糖尿病肾病中起作用，我们评估了来自牛（b）GH或bGHA转基因（Tg）小鼠及其非转基因（NTg）同窝仔鼠（无论有无STZ诱导的糖尿病）的肝脏和肾脏中GHR/GH结合蛋白的GH特异性结合和信使RNA水平。我们发现，与NTg对照相比，bGH-和bGHA-Tg小鼠的肝脏特异性GH结合均显著更高。相反，与NTg同窝仔鼠相比，bGH-Tg小鼠的肾脏GH结合显著更低。这些结果表明，小鼠GHR表达的调节具有组织特异性。STZ诱导的糖尿病降低了NTg和GHA-Tg小鼠肝脏和肾脏中的GH特异性结合，但未降低bGH-Tg小鼠中的结合。糖尿病NTg和GHA-Tg小鼠中GHR结合的降低表明胰岛素参与了GHR表达的调节。GHA-Tg小鼠中肾脏GHR的下调与GHA的存在相结合，可能部分解释了GHA对糖尿病肾脏病变的保护机制。
