SOMATOSTATIN MESSENGER-RNA IN HYPOTHALAMIC NEURONS IS INCREASED BY TESTOSTERONE THROUGH ACTIVATION OF ANDROGEN RECEPTORS AND NOT BY AROMATIZATION TO ESTRADIOL
SOMATOSTATIN MESSENGER-RNA IN HYPOTHALAMIC NEURONS IS INCREASED BY TESTOSTERONE THROUGH ACTIVATION OF ANDROGEN RECEPTORS AND NOT BY AROMATIZATION TO ESTRADIOL
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DOI：
10.1159/000125618
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发表时间：
1990-10-01
影响因子：
4.1
通讯作者：
CLIFTON, DK
中科院分区：
文献类型：
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作者：
ARGENTE, J;CHOWENBREED, JA;CLIFTON, DK
生长激素 (GH) 的分泌模式至少部分通过调节下丘脑生长抑素 (SS) 和 GH 释放激素的分泌而受到性类固醇的影响。表达 SS 信使 RNA (mRNA) 的室周核 (PeN) 中的神经元受到睾酮生理水平的调节。然而，尚不确定睾酮的作用是直接由雄激素受体激活介导，还是通过芳构化为雌二醇并随后与雌激素受体结合间接介导。我们通过评估 17.β-雌二醇和不可芳香化雄激素二氢睾酮 (DHT) 模拟睾酮作用的有效性来研究这个问题。成年雄性大鼠被阉割并皮下植入含有睾酮、17β-雌二醇或DHT的硅橡胶胶囊或假胶囊。对完整的动物进行假手术。我们使用原位杂交来评估这些治疗对下丘脑单个神经元 SS mRNA 信号水平的影响。去势后，PeN 细胞中的 SS mRNA 含量减少（完整的，195.+-.12 粒/细胞，对比去势的，139.+-.4 粒/细胞）。用生理水平的睾酮替代可防止SS mRNA信号水平的下降（去势睾酮替代，214.+-.15颗粒/细胞），与用不可芳香化雄激素DHT（去势DHT替代，213.+-.16颗粒/细胞）替代一样。用17.β.-雌二醇治疗未能阻止去势后SS mRNA含量的下降（去势雌激素替代，145.+-.4粒/细胞）。去势17β-雌二醇处理的动物与去势假处理处理的动物没有显着差异(去势，139.+-.4粒/细胞，对比去势雌激素替代，145.+-.4粒/细胞)。这些结果表明，虽然睾酮和DHT阻止了SS mRNA信号水平的去势后下降，但17β-雌二醇却没有这种作用。基于这些观察，我们得出结论，睾酮刺激 PeN 神经元中 SS 基因表达的能力可能是通过雄激素受体的激活介导的，而不是通过芳构化为雌二醇来介导的。
Growth hormone (GH) secretory patterns are influenced by sex steroids, at least in part, through modulation of the secretion of hypothalamic somatostatin (SS) and GH-releasing hormone. Neurons in the periventricular nucleus (PeN) expressing the messenger RNA (mRNA) for SS are modulated by physiological levels of testosterone. However, it is uncertain whether testosterone''s action is mediated directly by androgen receptor activation or indirectly through aromatization to estradiol and subsequent binding to the estrogen receptor. We examined this question by evaluating the effectiveness of 17.beta.-estradiol and the nonaromatizable androgen, dihydrotestosterone (DHT), to mimic the effects of testosterone. Adult male rats were castrated and implanted subcutaneously with a Silastic capsule that contained either testosterone, 17.beta.-estradiol or DHT, or a sham capsule. Intact animals were sham-operated. We used in situ hybridization to assess the effect of these treatments on SS mRNA signal levels in individual neurons of the hypothalamus. Following castration, SS mRNA content was reduced in cells of the PeN (intact, 195 .+-. 12 grains/cell, vs. castrated, 139 .+-. 4 grains/cell). Replacement with physiological levels of testosterone prevented the decline in SS mRNA signal levels (castrated testosterone-replaced, 214 .+-. 15 grains/cell) as did replacement with the nonaromatizable androgen DHT (castrated DHT-replaced, 213 .+-. 16 grains/cell). Treatment with 17.beta.-estradiol failed to prevent the postcastration decline in SS mRNA content (castrated estrogen-replaced, 145 .+-. 4 grains/cell). Castrated 17.beta.-estradiol-treated animals were not significantly different from the castrated sham-treated animals (castrated, 139 .+-. 4 grains/cell, vs. castrated estrogen-replaced, 145 .+-. 4 grains/cell). These results show that, whereas testosterone and DHT prevented the postcastration decline in SS mRNA signal levels, 17.beta.-estradiol had no such effect. Based on these observations, we conclude that the ability of testosterone to stimulate SS gene expression in neurons of the PeN is likely to be mediated through activation of androgen receptors and not through aromatization to estradiol.