PROOPIOMELANOCORTIN MESSENGER-RNA IN HYPOTHALAMIC NEURONS IS INCREASED BY TESTOSTERONE THROUGH AROMATIZATION TO ESTRADIOL
PROOPIOMELANOCORTIN MESSENGER-RNA IN HYPOTHALAMIC NEURONS IS INCREASED BY TESTOSTERONE THROUGH AROMATIZATION TO ESTRADIOL
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DOI：
10.1159/000125647
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发表时间：
1990-12-01
影响因子：
4.1
通讯作者：
STEINER, RA
中科院分区：
文献类型：
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作者：
CHOWEN, JA;ARGENTE, J;STEINER, RA
我们先前已经证明，在吻侧弓状核表达前阿片黑素皮质素(POMC)信使RNA(MRNA)的神经元对生理水平的睾酮的调节有反应。然而，目前还不确定睾酮S的作用是通过直接激活雄激素受体还是通过芳构化成雌二醇并随后与雌激素受体结合来介导的。我们通过评估雌二醇和双氢睾酮(DHT)在逆转去势诱导的弓状核POMC mRNA减少方面的有效性来研究这个问题。用原位杂交技术检测了正常、去势、去势睾酮替代、去势雌二醇替代和去势DHT替代雄性大鼠弓状神经元中POMC mRNA的含量。成年雄性大鼠去势后植入(S.C.)用硅橡胶胶囊填充到下列规格之一：结晶睾酮(30 mm；n=4)；17β-雌二醇(E2)与胆固醇1：1稀释(5 mm；n=4)；DHT(40 mm；n=4)；或空(30 mm；n=4)。对照组、假手术组(n=4)保持完好。对结果的分析表明，去势后，弓状核细胞中POMC mRNA的含量显著减少(完整：152。+-。3粒/细胞与去势：110。+-。3粒/细胞)。用生理水平的睾酮替代可阻止POMC信使核糖核酸水平的下降(去势的睾酮-替代：143。+-。6粒/细胞)，以及生理水平的雌激素替代(去势雌激素-替代：149.+-。8粒/细胞)。DHT处理未能阻止去势后POMC mRNA含量的下降(去势后DHT处理：118.+-。4粒/细胞)。这些结果表明，睾酮和雌激素可阻止去势后POMC基因表达的下降，而非芳香化雄激素DHT则无此作用。基于这些观察，我们得出结论，睾酮刺激POMC基因表达的能力可能是通过雌激素受体的芳构化和随后的激活来介导的。
We have previously demonstrated that neurons in the rostral arcuate nucleus expressing the messenger RNA (mRNA) for pro-opiomelanocortin (POMC) are responsive to modulation by physiological levels of testosterone. It is uncertain, however, whether testosterone''s action is mediated through direct activation of androgen receptors or through aromatization to estradiol and subsequent binding to estrogen receptors. We examined this question by evaluating the effectiveness of estradiol and dihydrotestosterone (DHT), a nonaromatizable androgen, in reversing the castration-induced diminution of POMC mRNA in the arcuate nucleus. Using in situ hybridization, we measured POMC mRNA content within arcuate neurons of intact, castrated, castrated testosterone-replaced, castrated estradiol-replaced, and castrated DHT-replaced male rats. Adult male rats were castrated and implanted (s.c.) with a Silastic capsule filled to one of the following specifications: crystalline testosterone (30 mm; n = 4); 17.beta.-estradiol (E2) diluted 1:1 with cholesterol (5 mm; n = 4); DHT (40 mm; n = 4); or empty (30 mm; n = 4). Control, sham-operated animals (n = 4) were left intact. Analysis of the results showed that following castration, POMC mRNA content was significantly reduced in cells of the arcuate nucleus (intact: 152 .+-. 3 grains/cell vs. castrate: 110 .+-. 3 grains/cell). Replacement with physiological levels of testosterone prevented the decline in POMC mRNA levels (castrated testosterone-replaced: 143 .+-. 6 grains/cell), as did replacement with physiological levels of estrogen (castrated estrogen-replaced: 149 .+-. 8 grains/cell). Treatment with DHT failed to prevent the postcastration decline in POMC mRNA content (castrated DHT-treated: 118 .+-. 4 grains/cell). These results show that whereas testosterone and estrogen prevent the postcastration decline in POMC mRNA, the nonaromatizable androgen DHT had no such effect. Based on these observations, we conclude that the ability of testosterone to stimulate POMC gene expression is likely to be mediated through aromatization and subsequent activation of estrogen receptors.