Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
J Clin Endocrinol Metab. 2012 Apr;97(4):E521-7. doi: 10.1210/jc.2011-3347. Epub 2012 Feb 8.
In men, GH secretion is stimulated by estradiol derived locally from aromatization of testosterone. Recently, we showed that local estrogen also plays a major role in the central regulation of GH secretion in women. Tamoxifen and raloxifene are selective estrogen receptor modulators (SERMs), drugs that block central estrogen action but exert estrogen-like effects in the liver, inhibiting hepatic IGF-I production. The relative impact of SERMs on the GH-IGF-I axis in men and women has not been investigated.
The aim of the study was to determine whether there is a gender difference in the impact of SERMs on the GH-IGF-I axis.
We conducted a comparative, randomized, open-label, crossover study of tamoxifen and raloxifene.
Ten healthy postmenopausal women and ten healthy men were randomized to 2-wk sequential treatment with tamoxifen (10 and 20 mg/d) and raloxifene (60 and 120 mg/d) with a washout of 2 wk between treatments.
The GH response to arginine, IGF-I, testosterone, and SHBG was measured.
In women, but not in men, tamoxifen significantly attenuated the GH response to arginine. The GH response was not significantly blunted by raloxifene in both sexes. Both SERMs significantly reduced mean IGF-I levels to a similar degree in men and women. In men, both SERMs significantly increased LH and testosterone levels.
In summary, GH secretion was blunted by tamoxifen in women in the face of reduced IGF-I feedback inhibition but not in men in whom the gonadal axis was stimulated. We conclude that potential blunting of GH secretion in men by SERMs was counteracted by concomitant central stimulation of GH secretion by testosterone. In therapeutic doses, tamoxifen may induce detrimental metabolic effects in women, but not men.
在男性中，GH 的分泌受到源自睾酮芳香化的内源性雌激素的刺激。最近，我们发现局部雌激素在女性 GH 分泌的中枢调节中也起着主要作用。他莫昔芬和雷洛昔芬是选择性雌激素受体调节剂（SERMs），这些药物可阻断中枢雌激素作用，但在肝脏中发挥类雌激素作用，抑制肝脏 IGF-I 的产生。SERMs 对男性和女性 GH-IGF-I 轴的相对影响尚未得到研究。
本研究旨在确定 SERMs 对 GH-IGF-I 轴的影响是否存在性别差异。
我们进行了一项比较、随机、开放标签、交叉研究，比较了他莫昔芬和雷洛昔芬的作用。
10 名健康绝经后妇女和 10 名健康男性被随机分为 2 周序贯治疗，分别接受他莫昔芬（10 和 20mg/d）和雷洛昔芬（60 和 120mg/d）治疗，两种药物治疗之间有 2 周的洗脱期。
测定了 GH 对精氨酸、IGF-I、睾酮和 SHBG 的反应。
在女性中，但在男性中，他莫昔芬显著减弱了 GH 对精氨酸的反应。两种 SERMs 在两性中均未显著减弱 GH 对雷洛昔芬的反应。两种 SERMs 均显著降低了男女 IGF-I 水平，程度相似。在男性中，两种 SERMs 均显著增加了 LH 和睾酮水平。
总之，在面对 IGF-I 反馈抑制降低的情况下，他莫昔芬在女性中削弱了 GH 分泌，但在男性中并未削弱，因为男性的性腺轴受到了刺激。我们得出结论，SERMs 潜在地削弱了男性的 GH 分泌，但被睾酮对 GH 分泌的中枢刺激所抵消。在治疗剂量下，他莫昔芬可能会在女性中引起有害的代谢影响，但不会在男性中引起。
