Testosterone alters iron metabolism and stimulates red blood cell production independently of dihydrotestosterone
Testosterone alters iron metabolism and stimulates red blood cell production independently of dihydrotestosterone
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DOI：
10.1152/ajpendo.00184.2014
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发表时间：
2014-09-01
影响因子：
5.1
通讯作者：
Borst, Stephen E.
中科院分区：
文献类型：
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作者：
Beggs, Luke A.;Yarrow, Joshua F.;Borst, Stephen E.
睾酮(T)刺激红细胞生成和调节铁稳态。然而，尚不清楚是否（II型）5 α - T还原为二氢睾酮（DHT）介导了这些雄激素效应，就像在其他一些组织中一样。我们的目的是确定抑制II型5 α -还原酶（通过非那雄胺）是否会改变老年性腺功能低下男性服用睾酮-烯酸（TE）后红细胞（RBC）的产生和铁稳态的血清标志物。60名年龄在bb0 ~ 60岁、血清T < 300 ng/dl或生物可利用T < 70 ng/dl的男性，采用2 × 2因子设计，接受TE （125 mg/周）、非那雄胺（5 mg/天）和安慰剂的对照治疗。在12个月的治疗过程中，TE使红细胞计数增加9%，红细胞压积增加4%，血红蛋白增加8%，同时抑制血清hepcidin 57%（所有测量值P < 0.001）。上述大多数变化发生在治疗的前3个月，非那雄胺的联合使用并没有显著改变这些影响。TE还在治疗开始的3个月内降低了32%的血清铁蛋白（P = 0.002），而没有改变铁、转铁蛋白或转铁蛋白饱和度。我们得出结论，TE刺激红细胞生成和改变铁稳态独立于II型5 α还原酶。这些结果表明，雄激素介导的红细胞生成或铁稳态的改变并不需要DHT升高，而铁稳态的改变似乎支持铁并入红细胞。
Testosterone (T) stimulates erythropoiesis and regulates iron homeostasis. However, it remains unknown whether the (type II) 5 alpha-reduction of T to dihydrotestosterone (DHT) mediates these androgenic effects, as it does in some other tissues. Our purpose was to determine whether inhibition of type II 5 alpha-reductase (via finasteride) alters red blood cell (RBC) production and serum markers of iron homeostasis subsequent to testosterone-enanthate (TE) administration in older hypogonadal men. Sixty men aged >60 yr with serum T < 300 ng/dl or bioavailable T < 70 ng/dl received treatment with TE (125 mg/wk) vs. vehicle paired with finasteride (5 mg/day) vs. placebo using a 2 x 2 factorial design. Over the course of 12 mo, TE increased RBC count 9%, hematocrit 4%, and hemoglobin 8% while suppressing serum hepcidin 57% (P < 0.001 for all measurements). Most of the aforementioned changes occurred in the first 3 mo of treatment, and finasteride coadministration did not significantly alter any of these effects. TE also reduced serum ferritin 32% (P = 0.002) within 3 mo of treatment initiation without altering iron, transferrin, or transferrin saturation. We conclude that TE stimulates erythropoiesis and alters iron homeostasis independently of the type II 5 alpha-reductase enzyme. These results demonstrate that elevated DHT is not required for androgen-mediated erythropoiesis or for alterations in iron homeostasis that would appear to support iron incorporation into RBCs.