A transcriptome-wide screen for mRNAs enriched in fetal Leydig cells: CRHR1 agonism stimulates rat and mouse fetal testis steroidogenesis.
A transcriptome-wide screen for mRNAs enriched in fetal Leydig cells: CRHR1 agonism stimulates rat and mouse fetal testis steroidogenesis.
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DOI：
10.1371/journal.pone.0047359
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Johnson KJ
中科院分区：
文献类型：
--
作者：
McDowell EN;Kisielewski AE;Pike JW;Franco HL;Yao HH;Johnson KJ
胎儿睾丸类固醇合成在男性胎儿的生殖发育中起重要作用。虽然类固醇生成的某些方面的调节剂是已知的，但人类和啮齿动物胎儿睾丸中类固醇生成的最初驱动因素尚不清楚。通过比较分析啮齿动物胎儿睾丸基因芯片数据集，确定了54个候选胎儿Leydig细胞特异性基因。胎鼠睾丸间质表达的一个子集，这些基因与未知的表达（Crhr 1，Gramd 1b，Itih 5，Vgll 3，和Vsnl 1）进行了验证，通过整体安装原位杂交。在候选胎儿Leydig细胞特异性因子中，使用用受体激动剂（CRH、PRL和PROK2）处理的离体胎儿睾丸测试三种受体（CRHR1、PRLR和PROKR2）的类固醇生成功能。虽然PRL和PROK 2没有影响，但CRH在低浓度（约1至10 nM）下增加了GD15小鼠和GD17大鼠睾丸中类固醇生成基因Cyp11 a1、Cyp17 a1、Scarb 1和星星的表达，同时增加了睾酮的产生。GD15胎鼠睾丸暴露于特定CRHR1拮抗剂减弱了CRH诱导的类固醇基因表达和睾酮反应。与离体啮齿动物胎儿睾丸相似，MA-10 Leydig细胞暴露≥ 10 nM CRH可增加类固醇生成途径mRNA和孕酮水平，表明CRH可通过直接靶向Leydig细胞增强类固醇生成。胎鼠下丘脑有CRh mRNA表达，胎鼠羊水中有CRH肽表达。总之，这些数据提供了一个资源，发现控制胎儿Leydig细胞生物学的因素，并表明CRHR1激活CRH刺激大鼠和小鼠胎儿Leydig细胞类固醇激素在体内。
Fetal testis steroidogenesis plays an important role in the reproductive development of the male fetus. While regulators of certain aspects of steroidogenesis are known, the initial driver of steroidogenesis in the human and rodent fetal testis is unclear. Through comparative analysis of rodent fetal testis microarray datasets, 54 candidate fetal Leydig cell-specific genes were identified. Fetal mouse testis interstitial expression of a subset of these genes with unknown expression (Crhr1, Gramd1b, Itih5, Vgll3, and Vsnl1) was verified by whole-mount in situ hybridization. Among the candidate fetal Leydig cell-specific factors, three receptors (CRHR1, PRLR, and PROKR2) were tested for a steroidogenic function using ex vivo fetal testes treated with receptor agonists (CRH, PRL, and PROK2). While PRL and PROK2 had no effect, CRH, at low (approximately 1 to 10) nM concentration, increased expression of the steroidogenic genes Cyp11a1, Cyp17a1, Scarb1, and Star in GD15 mouse and GD17 rat testes, and in conjunction, testosterone production was increased. Exposure of GD15 fetal mouse testis to a specific CRHR1 antagonist blunted the CRH-induced steroidogenic gene expression and testosterone responses. Similar to ex vivo rodent fetal testes, ≥10 nM CRH exposure of MA-10 Leydig cells increased steroidogenic pathway mRNA and progesterone levels, showing CRH can enhance steroidogenesis by directly targeting Leydig cells. Crh mRNA expression was observed in rodent fetal hypothalamus, and CRH peptide was detected in rodent amniotic fluid. Together, these data provide a resource for discovering factors controlling fetal Leydig cell biology and suggest that CRHR1 activation by CRH stimulates rat and mouse fetal Leydig cell steroidogenesis in vivo.
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影响因子：
3.6
作者：
Huang, BM;Stocco, DM;Norman, RL
通讯作者：
Norman, RL
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
4.8
作者：
Donaldson, CJ;Sutton, SW;Vale, WW
通讯作者：
Vale, WW
影响因子：
4.8
作者：
ASCOLI, M
通讯作者：
ASCOLI, M
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP