Ontogeny of region-specific sex differences in androgen receptor messenger ribonucleic acid expression in the rat forebrain.

Ontogeny of region-specific sex differences in androgen receptor messenger ribonucleic acid expression in the rat forebrain.
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DOI:
10.1210/endo.139.4.5940
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发表时间:
1998-04
期刊:
影响因子:
4.8
通讯作者:
M. McAbee;L. Doncarlos
M. McAbee;L. Doncarlos
中科院分区:
医学2区
文献类型:
--
作者:
M. McAbee;L. Doncarlos

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睾酮及其代谢物是负责大脑性别分化的主要性腺激素。然而,由于睾酮在细胞内代谢为活性雄激素和雌激素化合物,雄激素受体(AR)与雌激素受体在这一过程中特定方面的相对作用尚不清楚。在这项研究中,我们使用35s标记的核糖核酸探针和原位杂交分析了AR信使RNA (mRNA)在发育中的终纹床核、内侧视前区和外侧隔以及下丘脑腹内侧核和弓状核中的稳态相对表达水平。在胚胎第20天和出生后第0、4、10和20天检测每个区域,以获得AR mRNA表达的发育谱。所有地区在胚胎第20天均存在AR mRNA杂交。此外,在整个围产期,在男性和女性的所有检查区域,AR mRNA的表达都有所增加。然而,在出生后第4天至第10天,雄性终纹床核主体部分和内侧视前区AR mRNA表达急剧增加,而雌性则没有这种情况。随后,在出生后第10天,雄性在这些区域的AR mRNA水平高于雌性。在任何年龄,侧隔、腹内侧核和弓形核的AR mRNA含量均无性别差异。这些结果表明,发育过程中AR mRNA表达的性别差异可能导致对雄激素潜在男性化效应敏感性的早期性别差异。
Testosterone and its metabolites are the principal gonadal hormones responsible for sexual differentiation of the brain. However, the relative roles of the androgen receptor (AR) vs. the estrogen receptor in specific aspects of this process remain unclear due to the intracellular metabolism of testosterone to active androgenic and estrogenic compounds. In this study, we used an 35S-labeled riboprobe and in situ hybridization to analyze steady state, relative levels of AR messenger RNA (mRNA) expression in the developing bed nucleus of the stria terminalis, medial preoptic area, and lateral septum, as well as the ventromedial and arcuate nuclei of the hypothalamus. Each area was examined on embryonic day 20 and postnatal days 0, 4, 10, and 20 to produce a developmental profile of AR mRNA expression. AR mRNA hybridization was present on embryonic day 20 in all areas analyzed. In addition, AR mRNA expression increased throughout the perinatal period in all areas examined in both males and females. However, between postnatal days 4 and 10, sharp increases in AR mRNA expression in the principal portion of the bed nucleus of the stria terminalis and the medial preoptic area occurred in the male that were not paralleled in the female. Subsequently, males exhibited higher levels of AR mRNA than females in these areas by postnatal day 10. There was no sex difference in AR mRNA content in the lateral septum, ventromedial nucleus, or arcuate nucleus at any age. These results suggest that sex differences in AR mRNA expression during development may lead to an early sex difference in sensitivity to the potential masculinizing effects of androgen.