睾酮对低促性腺激素性性腺功能减退症合并2型糖尿病患者的铁调素、铁转运蛋白、铁蛋白及铁结合能力的影响。
Effect of testosterone on hepcidin, ferroportin, ferritin and iron binding capacity in patients with hypogonadotropic hypogonadism and type 2 diabetes.
作者信息
Dhindsa Sandeep, Ghanim Husam, Batra Manav, Kuhadiya Nitesh D, Abuaysheh Sanaa, Green Kelly, Makdissi Antoine, Chaudhuri Ajay, Dandona Paresh
机构信息
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, NY, USA.
Division of Endocrinology, Diabetes and Metabolism, Texas Tech University Health Sciences Center, Odessa, TX, USA.
出版信息
Clin Endocrinol (Oxf). 2016 Nov;85(5):772-780. doi: 10.1111/cen.13130. Epub 2016 Jul 18.
CONTEXT
As the syndrome of hypogonadotropic hypogonadism (HH) is associated with anaemia and the administration of testosterone restores haematocrit to normal, we investigated the potential underlying mechanisms.
DESIGN
Randomized, double-blind, placebo-controlled trial.
METHODS
We measured basal serum concentrations of erythropoietin, iron, iron binding capacity, transferrin (saturated and unsaturated), ferritin and hepcidin and the expression of ferroportin and transferrin receptor (TR) in peripheral blood mononuclear cells (MNC) of 94 men with type 2 diabetes. Forty-four men had HH (defined as subnormal free testosterone along with low or normal LH concentrations) while 50 were eugonadal. Men with HH were randomized to testosterone or placebo treatment every 2 weeks for 15 weeks. Blood samples were collected at baseline, 3 and 15 weeks after starting treatment. Twenty men in testosterone group and 14 men in placebo group completed the study.
RESULTS
Haematocrit levels were lower in men with HH (41·1 ± 3·9% vs 43·8 ± 3·4%, P = 0·001). There were no differences in plasma concentrations of hepcidin, ferritin, erythropoietin, transferrin or iron, or in the expression of ferroportin or TR in MNC among HH and eugonadal men. Haematocrit increased to 45·3 ± 4·5%, hepcidin decreased by 28 ± 7% and erythropoietin increased by 21 ± 7% after testosterone therapy (P < 0·05). There was no significant change in ferritin concentrations, but transferrin concentration increased while transferrin saturation and iron concentrations decreased (P < 0·05). Ferroportin and TR mRNA expression in MNC increased by 70 ± 13% and 43 ± 10%, respectively (P < 0·01), after testosterone therapy.
CONCLUSIONS
The increase in haematocrit following testosterone therapy is associated with an increase in erythropoietin, the suppression of hepcidin, and an increase in the expression of ferroportin and TR.
背景
由于低促性腺激素性性腺功能减退（HH）综合征与贫血相关，且给予睾酮可使血细胞比容恢复正常，我们对其潜在的机制进行了研究。
设计
随机、双盲、安慰剂对照试验。
方法
我们测量了94例2型糖尿病男性患者的基础血清促红细胞生成素、铁、铁结合能力、转铁蛋白（饱和与不饱和）、铁蛋白和铁调素浓度，以及外周血单个核细胞（MNC）中铁转运蛋白和转铁蛋白受体（TR）的表达。44例男性患有HH（定义为游离睾酮低于正常水平且促黄体生成素浓度低或正常），50例性腺功能正常。患有HH的男性每2周随机接受睾酮或安慰剂治疗，持续15周。在基线、开始治疗后3周和15周采集血样。睾酮组20例男性和安慰剂组14例男性完成了研究。
结果
HH男性的血细胞比容水平较低（41.1±3.9%对43.8±3.4%，P = 0.001）。HH男性和性腺功能正常男性之间，血浆铁调素、铁蛋白、促红细胞生成素、转铁蛋白或铁的浓度，以及MNC中铁转运蛋白或TR的表达没有差异。睾酮治疗后，血细胞比容升至45.3±4.5%，铁调素降低28±7%，促红细胞生成素增加21±7%（P < 0.05）。铁蛋白浓度无显著变化，但转铁蛋白浓度增加，而转铁蛋白饱和度和铁浓度降低（P < 0.05）。睾酮治疗后，MNC中铁转运蛋白和TR mRNA表达分别增加70±13%和43±10%（P < 0.01）。
结论
睾酮治疗后血细胞比容的增加与促红细胞生成素的增加、铁调素的抑制以及铁转运蛋白和TR表达的增加有关。
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