Molecular profiling of postnatal development of the hypothalamus in female and male rats.
Molecular profiling of postnatal development of the hypothalamus in female and male rats.
复制标题
雌性和雄性大鼠下丘脑产后发育的分子谱。
DOI：
10.1095/biolreprod.112.102798
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发表时间：
2012
影响因子：
3.6
通讯作者：
Gore,AndreaC
中科院分区：
文献类型：
--
作者：
Walker,DeenaM;Kirson,Dean;Perez,LorenzoF;Gore,AndreaC
生殖功能在出生后发育过程中是高度动态的。在这里，我们进行了发育中的雄性和雌性大鼠的下丘脑的基因表达模式的分子分析，以确定哪些基因是性二态的，以深入了解下丘脑基因的一个更复杂的网络，并确定它们之间的关系的动态变化，并与性类固醇激素在发展过程中。使用低密度PCR平台，我们量化了视前区（POA）和内侧基底下丘脑（MBH）的mRNA水平，并测定了从出生到成年的6个年龄段的循环雌二醇、睾酮和孕酮。许多基因经历了发育变化，特别是出生后的增加，减少，或在青春期的高峰/高原。令人惊讶的是，几乎没有性别差异;只有Esr 1，Kiss 1和Tac 2是双态的（女性较高）。基因表达的聚类分析显示POA的性二态相关性，但从P30（出生后第30天）到P60的MBH没有。激素测量显示，雌二醇的发展概况的性别差异不大;孕酮水平较高的女性仅在P30后;和睾酮的发展模式，在P30的最低点，然后通过P60（男性）的显着增加。此外，bionetwork分析显示，下丘脑基因表达谱及其与激素的关系经历了与成人大不相同的动态发育变化。这些数据强调了发育阶段在考虑激素对下丘脑神经内分泌基因调节的影响方面的重要性。此外，发现很少神经内分泌基因的性二态性突出了需要考虑产后发展的网络方法，允许评估的相互作用和表达模式。
Reproductive function is highly dynamic during postnatal developmental. Here, we performed molecular profiling of gene expression patterns in the hypothalamus of developing male and female rats to identify which genes are sexually dimorphic, to gain insight into a more complex network of hypothalamic genes, and to ascertain dynamic changes in their relationships with one another and with sex steroid hormones during development. Using a low-density PCR platform, we quantified mRNA levels in the preoptic area (POA) and medial basal hypothalamus (MBH), and assayed circulating estradiol, testosterone, and progesterone at six ages from birth through adulthood. Numerous genes underwent developmental change, particularly postnatal increases, decreases, or peaks/plateaus at puberty. Surprisingly, there were few sex differences; onlyEsr1, Kiss1,andTac2were dimorphic (higher in females). Cluster analysis of gene expression revealed sexually dimorphic correlations in the POA but not the MBH from P30 (Postnatal Day 30) to P60. Hormone measurements showed few sex differences in developmental profiles of estradiol; higher levels of progesterone in females only after P30; and a developmental pattern of testosterone with a nadir at P30 followed by a dramatic increase through P60 (males). Furthermore, bionetwork analysis revealed that hypothalamic gene expression profiles and their relationships to hormones undergo dynamic developmental changes that differ considerably from adults. These data underscore the importance of developmental stage in considering the effects of hormones on the regulation of neuroendocrine genes in the hypothalamus. Moreover, the finding that few neuroendocrine genes are sexually dimorphic highlights the need to consider postnatal development from a network approach that allows assessment of interactions and patterns of expression.