Deletion of the Igf1 gene: suppressive effects on adult Leydig cell development.
Deletion of the Igf1 gene: suppressive effects on adult Leydig cell development.
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DOI：
10.2164/jandrol.109.008680
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发表时间：
2010-07
影响因子：
--
通讯作者：
Ge RS
中科院分区：
文献类型：
--
作者：
Hu GX;Lin H;Chen GR;Chen BB;Lian QQ;Hardy DO;Zirkin BR;Ge RS
先前的研究表明，胰岛素样生长因子1(IGF1)基因的缺失会导致35d龄小鼠睾丸中间质细胞数量的减少，并导致循环中的睾酮水平下降。在目前的研究中，我们询问了Igf1基因的缺失是否会影响导致成人间质细胞(ALCs)建立的发育序列中某些或所有前体细胞类型的数量、增殖和/或类固醇生成功能。出生后14-90天的β-−/−小鼠睾丸间质细胞系(即3个Ig-羟类固醇脱氢酶阳性细胞)数量较年龄匹配的Ig F_1+/+对照组明显减少。ALCS的发育始于干细胞(SLCs)、祖细胞(PLC)和未成熟间质细胞(ILCs)。IgF1−/−和IgF1+/+小鼠SLC的溴脱氧尿嘧啶核苷标记指数相似。相反，在PND14至PND35的每一天，Igf1−/−小鼠的PLC的标记指数降低，而更成熟的间质细胞(在此被称为LCS，ILC+ALC的组合)的标记指数从PND21至PND56降低。在接受重组IGF-I的Igf1−/−小鼠中，PLC和LCs的标记指数与年龄匹配的Igf1+/+小鼠相似，表明Igf1−/−小鼠的PLC和LCs的标记指数的降低是IGF-I减少的结果。在PND21至PND90的每一天，Igf1−/−小鼠的睾丸睾酮浓度显著降低，参与类固醇生成的睾丸特异mRNAs的表达也显著降低，包括Star、Cyp11a1和CyP17A1。5α还原酶基因(SRd5a1)在成人−/−睾丸中的表达增加，提示该基因的缺失可能抑制或延缓间质细胞的成熟。综上所述，这些观察表明，Igf1−/−小鼠成年睾丸中间质细胞数量的减少至少部分是由于ALC前体细胞的增殖和分化改变，而不是产生这些细胞的干细胞。
Deletion of the insulin-like growth factor 1 (Igf1) gene was shown in previous studies to result in reduced numbers of Leydig cells in the testes of 35-day-old mice, and in reduced circulating testosterone levels. In the current study, we asked whether deletion of the Igf1 gene affects the number, proliferation, and/or steroidogenic function of some or all of the precursor cell types in the developmental sequence that leads to the establishment of adult Leydig cells (ALCs). Decreased numbers of cells in the Leydig cell lineage (ie, 3β-hydroxysteroid dehydrogenase–positive cells) were seen in testes of postnatal day (PND) 14–90 Igf1−/− mice compared with age-matched Igf1+/+ controls. The development of ALCs proceeds from stem Leydig cells (SLCs) through progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs). The bromodeoxyuridine labeling index of putative SLCs was similar in the Igf1−/− and Igf1+/+ mice. In contrast, the labeling index of PLCs was reduced in the Igf1−/− mice on each day of PND 14 through PND 35, and that of more mature Leydig cells (referred to herein as LCs, a combination of ILCs plus ALCs) was reduced from PND 21 through PND 56. In Igf1−/− mice that received recombinant IGF-I, the labeling indices of PLCs and LCs were similar to those of age-matched Igf1+/+ mice, indicating that the reductions in the labeling indices seen in the PLCs and LCs of the Igf1−/− mice were a consequence of reduced IGF-I. On each day of PND 21 through PND 90, testicular testosterone concentrations were significantly reduced in the Igf1−/− mice, as were the expressions of testis-specific mRNAs involved in steroidogenesis, including Star, Cyp11a1, and Cyp17a1. The increased expression of the gene for 5α-reductase (Srd5a1) in adult Igf1−/− testes suggests that the depletion of Igf1 might suppress or delay Leydig cell maturation. These observations, taken together, indicate that the reduced numbers of Leydig cells in the adult testes of Igf1−/− mice result at least in part from altered proliferation and differentiation of ALC precursor cells, but not of the stem cells that give rise to these cells.
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影响因子：
3.6
作者：
Clark, AM;Garland, KK;Russell, LD
通讯作者：
Russell, LD
影响因子：
4.8
作者：
LIN, T;HASKELL, J;TERRACIO, L
通讯作者：
TERRACIO, L
影响因子：
4.8
作者：
Colon, Eugenia;Zaman, Farasat;Soder, Olle
通讯作者：
Soder, Olle
DOI：
10.1083/jcb.149.5.1019
发表时间：
2000-05-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gnessi L;Basciani S;Mariani S;Arizzi M;Spera G;Wang C;Bondjers C;Karlsson L;Betsholtz C
通讯作者：
Betsholtz C
影响因子：
4.8
作者：
HARDY, MP;ZIRKIN, BR;EWING, LL
通讯作者：
EWING, LL