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雄性大鼠视前区神经内分泌基因表达的发育概况

Developmental profiles of neuroendocrine gene expression in the preoptic area of male rats.

作者信息

Walker Deena M, Juenger Thomas E, Gore Andrea C

机构信息

Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712, USA.

出版信息

Endocrinology. 2009 May;150(5):2308-16. doi: 10.1210/en.2008-1396. Epub 2009 Jan 15.

Abstract

Reproductive function is controlled by GnRH cells and their steroid-sensitive regulatory inputs. The proper maturation of this system is critical to sexual development and maintenance of adult function. However, the molecular mechanisms underlying these developmental changes, and the potential roles of gonadal hormones in sculpting these processes, have not been fully explored. We performed a developmental profile from postnatal day (P) 1 through P60 of a network of five genes in the preoptic area (POA) that are critical to reproduction in male Sprague Dawley rats. GnRH, estrogen receptors-alpha, and -beta, androgen receptor (AR), and progesterone receptor (PR) mRNAs in the POA were assayed, and serum hormones were measured, in developing male rats. We also used a Taqman low-density array to identify candidate genes that may be important in development. Of the five targeted genes, only AR and PR changed robustly (7- and 3- to 4-fold increases, respectively) during development. All of the gonadal serum hormones changed markedly and with very different patterns from their receptor mRNAs: testosterone decreased from P1 to P30 and then increased to P60; progesterone peaked on P30; and estradiol decreased from P1 to P30. Using the Taqman low-density array, we identified several genes that changed dramatically in the POA with development, particularly G protein-coupled receptor 30, IGF-I, vitamin D receptor, estrogen-related receptor-alpha, and thyroid receptor-alpha. Our data demonstrate developmental stage-specific changes in neuroendocrine genes, particularly AR and PR. Moreover, the relationships between hormones and their corresponding receptors undergo dynamic changes across development in male rats.

摘要

生殖功能受促性腺激素释放激素(GnRH)细胞及其类固醇敏感调节输入的控制。该系统的正常成熟对于性发育和成年功能的维持至关重要。然而,这些发育变化背后的分子机制以及性腺激素在塑造这些过程中的潜在作用尚未得到充分探索。我们对雄性Sprague Dawley大鼠视前区(POA)中五个对生殖至关重要的基因网络进行了从出生后第1天(P1)到第60天(P60)的发育情况分析。在发育中的雄性大鼠中,检测了POA中的GnRH、雌激素受体α和β、雄激素受体(AR)以及孕激素受体(PR)的mRNA,并测量了血清激素。我们还使用Taqman低密度阵列来鉴定可能在发育中起重要作用的候选基因。在五个靶向基因中,只有AR和PR在发育过程中显著变化(分别增加了7倍和3至4倍)。所有性腺血清激素均发生了显著变化,且其模式与受体mRNA非常不同:睾酮从P1降至P30,然后升至P60;孕酮在P30达到峰值;雌二醇从P1降至P30。使用Taqman低密度阵列,我们鉴定出几个在POA中随发育而显著变化的基因,特别是G蛋白偶联受体30、胰岛素样生长因子-I、维生素D受体、雌激素相关受体α和甲状腺受体α。我们的数据表明神经内分泌基因存在发育阶段特异性变化,特别是AR和PR。此外,在雄性大鼠的发育过程中,激素与其相应受体之间的关系经历了动态变化。

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