Developmental Time Course of Estradiol, Testosterone, and Dihydrotestosterone Levels in Discrete Regions of Male and Female Rat Brain
Developmental Time Course of Estradiol, Testosterone, and Dihydrotestosterone Levels in Discrete Regions of Male and Female Rat Brain
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DOI：
10.1210/en.2010-0607
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发表时间：
2011-01-01
期刊：
影响因子：
4.8
通讯作者：
McCarthy, Margaret M.
中科院分区：
文献类型：
--
作者：
Konkle, Anne T. M.;McCarthy, Margaret M.
哺乳动物脑性分化的主流观点认为，在胎儿和新生儿睾丸中合成并在围产期集中芳香化的雄激素是脑内雌二醇的唯一来源，也是性别差异的主要决定因素。间脑的亚区是大脑中性别差异最大的区域之一，在围产期，下丘脑和视前区的睾酮和雌二醇量存在明显的性别差异。我们之前曾报道，在雄性和雌性新生大鼠的海马体和皮质中，雌二醇水平都出人意料地高。这促使了对大鼠大脑中类固醇发育状况的彻底调查，使用RIA对从胚胎19天到成年的大脑不同亚区的雌二醇、睾酮和双氢睾酮的水平进行了量化。当有足够的样本可用时，评估单个动物的血浆雌二醇水平。出生前下丘脑睾丸激素的显著性别差异与先前的发现一致。出生后，每个大脑区域的类固醇浓度都有明显的变化模式，这些与循环中的类固醇无关。在出生时摘除性腺和肾上腺并不能显著减少3天后检测的任何脑区的类固醇。在出生时，所有大脑区域都可以检测到芳香酶活性，活动水平的差异与观察到的雌二醇含量的地区差异平行。基于这些发现，我们认为大脑中的类固醇合成可能在哺乳动物的大脑发育中发挥关键作用，而不是建立性别差异。(内分泌学152：223-235,2011)
The prevailing view of sexual differentiation of mammalian brain is that androgen synthesized in the fetal and neonatal testis and aromatized centrally during a perinatal sensitive period is the sole source of brain estradiol and the primary determinant of sex differences. Subregions of the diencephalon are among the most sexually dimorphic in the brain, and there are well-established sex differences in the amount of testosterone and estradiol measured in the hypothalamus and preoptic area during the perinatal period. We previously reported unexpectedly high estradiol in the hippocampus and cortex of both male and female newborn rat. This prompted a thorough investigation of the developmental profile of steroids in the rat brain using RIA to quantify the level of estradiol, testosterone, and dihydrotestosterone in discrete subregions of the brain from embryonic d 19 to adulthood. Plasma estradiol levels from individual animals were assessed when sufficient sample was available. A significant sex difference in hypothalamic testosterone prior to birth was consistent with previous findings. Postnatally, there was a distinct pattern of changing steroid concentrations in each brain region, and these were unrelated to circulating steroid. Removal of the gonads and adrenals at birth did not significantly reduce steroids in any brain region assayed 3 d later. Aromatase activity was detectable in all brain areas at birth, and the difference in activity level paralleled the observed regional differences in estradiol content. Based on these findings, we propose that steroidogenesis in the brain, independent of peripherally derived precursors, may play a critical role in mammalian brain development of both sexes, beyond the establishment of sex differences. (Endocrinology 152: 223-235, 2011)