Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20057-1640, USA.
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA.
Biol Sex Differ. 2013 Jun 27;4:12. doi: 10.1186/2042-6410-4-12. eCollection 2013.
Human and animal studies support the idea that there are sex differences in the development of diabetic renal disease. Our lab and others have determined that in addition to Ang II (through the AT1R), growth hormone (GH) contributes to renal damage in models of renal failure; however, the impact of sex and GH on the mechanisms initiating diabetic renal disease is not known. This study examined the effect of sex and GH on parameters of renal damage in early, uncontrolled streptozotocin (STZ)-induced diabetes.
Adult male and female Sprague-Dawley rats were injected with vehicle (control), STZ, or STZ + GH and euthanized after 8 weeks.
Mild but significant glomerulosclerosis (GS) and tubulointerstitial fibrosis (TIF) was observed in both kidneys from male and female diabetic rats, with GH significantly increasing GS and TIF by 30% and 25% in male rats, but not in female rats. STZ increased TGF-β expression in both kidneys from male and female rats; however, while GH had no further effect on TGF-β protein in diabetic females, GH increased TGF-β protein in the male rat's kidneys by an additional 30%. This sex-specific increase in renal injury following GH treatment was marked by increased MCP-1 and CD-68+ cell density. STZ also reduced renal MMP-2 and MMP-9 protein expression in both kidneys from male and female rats, but additional decreases were only observed in GH-treated diabetic male rats. The sex differences were independent of AT1R activity.
These studies indicate that GH affects renal injury in diabetes in a sex-specific manner and is associated with an increase in pro-inflammatory mediators.
人体和动物研究支持这样一种观点，即在糖尿病肾病的发展过程中存在性别差异。我们的实验室和其他实验室已经确定，除了血管紧张素 II（通过 AT1R）之外，生长激素（GH）也会导致肾衰竭模型中的肾脏损伤；然而，性别和 GH 对引发糖尿病肾病的机制的影响尚不清楚。本研究探讨了性别和 GH 对早期未控制的链脲佐菌素（STZ）诱导的糖尿病中肾脏损伤参数的影响。
成年雄性和雌性 Sprague-Dawley 大鼠分别注射溶剂（对照）、STZ 或 STZ+GH，并在 8 周后处死。
雄性和雌性糖尿病大鼠的双侧肾脏均出现轻度但显著的肾小球硬化（GS）和肾小管间质纤维化（TIF），GH 使雄性大鼠的 GS 和 TIF 分别增加 30%和 25%，但对雌性大鼠无影响。STZ 增加了雄性和雌性大鼠双侧肾脏的 TGF-β表达；然而，GH 对糖尿病雌性大鼠肾脏中的 TGF-β 蛋白没有进一步影响，但 GH 使雄性大鼠肾脏中的 TGF-β 蛋白增加了 30%。GH 治疗后肾脏损伤的这种性别特异性增加表现为 MCP-1 和 CD-68+细胞密度增加。STZ 还降低了雄性和雌性大鼠双侧肾脏的 MMP-2 和 MMP-9 蛋白表达，但仅在 GH 治疗的糖尿病雄性大鼠中观察到进一步的降低。这些性别差异与 AT1R 活性无关。
这些研究表明，GH 以性别特异性的方式影响糖尿病中的肾脏损伤，并与促炎介质的增加有关。
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