Androgen supplementation during aging: development of a physiologically appropriate protocol.

Androgen supplementation during aging: development of a physiologically appropriate protocol.
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衰老过程中雄激素的补充:制定生理上适当的方案。

DOI:
10.1089/rej.2013.1518
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发表时间:
2014
影响因子:
2.6
通讯作者:
Kohama,StevenG
Kohama,StevenG
中科院分区:
医学3区
文献类型:
--
作者:
Urbanski,HenrykF;Sorwell,KrystinaG;Garyfallou,VasiliosT;Garten,Jamie;Weiss,Alison;Renner,Laurie;Neuringer,Martha;Kohama,StevenG

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男性表现出与年龄相关的循环睾酮(T)和脱氢表雄酮硫酸(DHEAS)水平下降。因此,有兴趣开发雄激素补充范式的老年人复制的激素谱的年轻人。在本研究中,我们以年龄较大(21-26岁)的雄性猕猴为模型,研究了雄激素补充模式的有效性,该模式包括晚上口服T (12 mg/kg体重,溶解在芝麻油/巧克力中),早上两次口服脱氢表雄酮(0.04 mg/kg体重,溶解在芝麻油/巧克力中),间隔3小时。重复补充激素5天后,在24小时内,每小时远程采集每只动物的连续血液样本,并检测皮质醇、DHEAS、T、5α-二氢睾酮(DHT)、雌酮(E1)和17β-雌二醇(E2)。补充雄激素后,睾酮水平显著升高,这与睾酮主要生物活性代谢物DHT、e1和E2在夜间持续升高有关。补充雄激素后血浆DHEAS水平也显著升高;DHEAS水平在清晨上升,并在一天中逐渐下降,与年轻人(7-12岁)的观察结果非常相似;相比之下,皮质醇水平未因补充而改变。总之,这些数据证明了一种非侵入性的雄激素补充模式,可以恢复老年雄性灵长类动物年轻时的循环雄激素水平。由于这种模式保留了自然循环的昼夜节律激素模式,我们预测它将产生更少的不良副作用,如睡眠紊乱或认知障碍。
Men show an age-related decline in the circulating levels of testosterone (T) and dehydroepiandrosterone sulfate (DHEAS). Consequently, there is interest in developing androgen supplementation paradigms for old men that replicate the hormone profiles of young adults. In the present study, we used old (21–26 years old) male rhesus monkeys as a model to examine the efficacy of an androgen supplementation paradigm that comprised oral T administration (12 mg/kg body weight, dissolved in sesame oil/chocolate) in the evening, and two oral DHEA administrations, 3 hr apart (0.04 mg/kg body weight, dissolved in sesame oil/chocolate) in the morning. After 5 days of repeated hormone supplementation, serial blood samples were remotely collected from each animal hourly across the 24-hr day, and assayed for cortisol, DHEAS, T, 5α-dihydrotestosterone (DHT), estrone (E1), and 17β-estradiol (E2). Following androgen supplementation, T levels were significantly elevated and this was associated with a more sustained nocturnal elevation of T's primary bioactive metabolites, DHT and E1and E2. Plasma DHEAS levels were also significantly elevated after androgen supplementation; DHEAS levels rose in the early morning and gradually declined during the course of the day, closely mimicking the profiles observed in young adults (7–12 years old); in contrast, cortisol levels were unaltered by the supplementation. Together the data demonstrate a non-invasive androgen supplementation paradigm that restores youthful circulating androgen levels in old male primates. Because this paradigm preserves the natural circulating circadian hormone patterns, we predict that it will produce fewer adverse side effects, such as perturbed sleep or cognitive impairment.
DOI: 10.1016/j.polymdegradstab.2009.11.020
发表时间: 2010-03-01
影响因子: 5.9
作者:
Quievy, N.;Jacquet, N.;Devaux, J.
通讯作者: Devaux, J.
衰老过程中补充激素:补充量和时间?
DOI: 10.1089/rej.2011.1251
发表时间: 2012
影响因子: 2.6
作者:
Sorwell,KG;Garten,J;Renner,L;Weiss,A;Garyfallou,VT;Kohama,SG;Neuringer,M;Urbanski,HF
通讯作者: Urbanski,HF