EFFECTS OF LONG-TERM ANDROGEN AND ESTRADIOL EXPOSURE ON THE HYPOTHALAMUS
EFFECTS OF LONG-TERM ANDROGEN AND ESTRADIOL EXPOSURE ON THE HYPOTHALAMUS
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DOI：
10.1210/endo-112-1-194
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发表时间：
1983-01-01
期刊：
影响因子：
4.8
通讯作者：
ROBAIRE, B
中科院分区：
文献类型：
--
作者：
BRAWER, J;SCHIPPER, H;ROBAIRE, B
越来越多的证据表明雌二醇可诱导大鼠下丘脑弓状核变性。相比之下，睾酮在这方面似乎相对惰性。睾丸激素诱导下丘脑损伤的相对无能可能解释了睾丸切除术对弓形核衰老变性的影响不足，而卵巢切除术则大大抑制了这一过程。因为下丘脑有一种酶系统可以将睾酮芳香化为雌二醇并将睾酮降低到5。-二氢睾酮（DHT），决定在下丘脑水平上研究这两种睾酮代谢物的作用和可能的相互作用。设计了一个下丘脑长期单独暴露于雌二醇、睾酮或二氢睾酮或雌二醇与睾酮或二氢睾酮联合暴露的系统。这是通过给切除卵巢的大鼠植入含有这些类固醇的缓释胶囊来实现的。通过测量弓形核中的小胶质细胞和星形细胞活性来评估暴露后下丘脑的变性。与空白对照相比，雌二醇植入动物的两种胶质细胞指数均显著增加，而睾酮植入动物的小胶质细胞活性略有增加，星形胶质细胞活性未增加。植入dht的动物表现出控制水平的神经胶质活性。然而，令人惊讶的是，双氢睾酮和雌二醇的联合治疗也显示出神经胶质活性的控制水平。持续低水平的雌二醇对弓形核和5 - α具有致病性。-减少雄激素可能在下丘脑水平上对雌二醇的神经致病作用发挥有效和直接的抑制作用。这两类睾酮代谢物之间的拮抗作用可能解释了睾酮相对无致病性和睾丸不参与下丘脑弓状核衰老的原因。
Evidence has accumulated indicating that estradiol induces degeneration in the hypothalamic arcuate nucleus of the rat. In contrast, testosterone appears to be relatively inert in this regard. The relative inability of testosterone to induce hypothalamic damage may account for the lack of effect of orchidectomy on senescent degeneration in the arcuate nucleus, whereas oophorectomy greatly suppresses this process. Since the hypothalamus has the enzyme system to aromatize testosterone to estradiol and that which reduces testosterone to 5.alpha.-dihydrotestosterone (DHT), it was decided to examine the effects and possible interaction of these 2 testosterone metabolites at the hypothalamic level. A system was designed in which the hypothalamus would receive long term exposure to estradiol, testosterone, or DHT alone or to estradiol combined with either testosterone or DHT. This was accomplished by implanting oophorectomized rats with sustained release capsules containing these steroids. Hypothalamic degeneration after the exposure was assessed by measuring microglial and astrocytic activity in the arcuate nucleus. Estradiol-implanted animals showed significant increases in both glial indices compared to blank-implanted controls, whereas testosterone-implanted animals showed a slight increase in microglial activity and no increase in astrocytic activity. DHT-implanted animals exhibited control levels of glial activity. Surprisingly, however, the combined treatment of DHT and estradiol also showed control levels of glial activity. Constant low levels of estradiol are pathogenic to the arcuate nucleus and 5.alpha.-reduced androgens may exert a potent and direct inhibitory effect on the neuropathogenic action of estradiol at the hypothalamic level. The antagonism between these 2 classes of testosterone metabolites may explain the relative nonpathogenicity of testosterone and the lack of participation of the testis in aging of the hypothalamic arcuate nucleus.