Cellular and molecular mechanisms that mediate insulin-dependent rat granulosa cell mitosis.
Cellular and molecular mechanisms that mediate insulin-dependent rat granulosa cell mitosis.
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介导胰岛素依赖性大鼠颗粒细胞有丝分裂的细胞和分子机制。
DOI：
10.1095/biolreprod52.1.124
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发表时间：
1995
影响因子：
3.6
通讯作者：
White,BA
中科院分区：
文献类型：
--
作者：
Peluso,JJ;Luciano,AM;Pappalardo,A;White,BA
大鼠卵泡由大小颗粒细胞（GC）组成。目前的研究表明，小GC在体外进行胰岛素或佛波酯依赖的有丝分裂。为了检查解释胰岛素促有丝分裂作用的细胞和分子事件，将小GC与胰岛素、佛波酯（TPA）或胰岛素和TPA两者一起培养。胰岛素和TPA分别使GC数比对照值增加21 ± 3%和20 ± 2%（p< 0.05）。同时添加胰岛素和TPA使GC数增加20 ± 3%（p< 0.05）。在第二个实验中，将小GC暴露于对照培养基、胰岛素、星形孢菌素（蛋白激酶C [PKC]抑制剂）或胰岛素和星形孢菌素。这些研究表明，胰岛素诱导GC数增加21%至5%，星形孢菌素阻断胰岛素的促有丝分裂作用。这些观察结果表明，胰岛素介导其促有丝分裂作用通过PKC依赖性机制。由于原癌基因c-fosandc-jun在GC有丝分裂期间表达，因此进行研究以确定这两种原癌基因产物的表达是否被胰岛素增强。免疫细胞化学法检测c-jos和c-jun蛋白的表达。这些研究表明，5小时后，胰岛素使forc-fos和c-jun染色的细胞百分比分别增加15 ± 2%和19 ± 4（p< 0.05）。这些原癌基因的表达被staurosporine阻断。孕酮和8-br-CAMP阻断胰岛素依赖的GC有丝分裂，也抑制c-jos和c-jun的表达。最后，在存在特异性forc-fos和c-jun的正义和反义寡核苷酸的情况下，将小GC与胰岛素一起培养。在这些条件下，在存在c-fos和c-jun正义寡核苷酸的情况下，胰岛素分别诱导细胞数量增加32 ± 10%和24 ± 5%。在eitherc-fosorc-jun反义寡核苷酸的存在下，胰岛素依赖性GC增殖被完全阻止。两者合计，这些实验支持的概念，胰岛素刺激小GC有丝分裂通过激活PKC，诱导bothc-fosandc-jun的表达。这两个基因在GC有丝分裂中发挥重要作用。
Rat ovarian follicles are composed of small and large granulosa cells (GC). The present studies demonstrate that small GCs undergo insulin- or phorbol ester-dependent mitosis in vitro. In order to examine the cellular and molecular events that account for insulin’s mitogenic action, small GCs were cultured with either insulin, phorbol ester (TPA), or both insulin and TPA. Insulin and TPA increased GC numbers by 21 ± 3% and 20 f 2% over control values, respectively (p< 0.05). Simultaneous addition of insulin and TPA increased GC numbers by 20 ± 3% (p< 0.05). In a second experiment, small GCs were exposed to control medium, insulin, staurosporine (a protein kinase C [PKC] inhibitor), or both insulin and staurosporine. These studies revealed that insulin induced a 21 f 5% increase in GC numbers and that staurosporine blocked insulin’s mitogenic action. These observations suggest that insulin mediates its mitogenic action through a PKC-dependent mechanism. Since the proto-oncogenes,c-fosandc-jun, are expressed during GC mitosis, studies were undertaken to determine whether or not the expression of these two proto-oncogenes products was enhanced by insulin. The expression ofc-josandc-junproteins was assessed by immunocytochemistry. These studies showed that after 5 h, insulin increased the percentage of cells that stained forc-fosandc-junby 15 ± 2% and 19 ± 4, respectively (p< 0.05). The expression of these proto-oncogenes was blocked by staurosporine. Both progesterone and 8-br-CAMP, which block insulin-dependent GC mitosis, also inhibited the expression ofc-josandc-jun. Finally, small GCs were cultured with insulin in the presence of sense and antisense oligonucleotides specific forc-fosandc-jun. Under these conditions, insulin induced a 32 ± 10% and 24 ± 5% increase in cell numbers in the presence ofc-fosandcjunsense oligonucleotides, respectively. Insulin-dependent GC proliferation was completely prevented in the presence of eitherc-fosorc-junantisense oligonucleotide. Taken together, these experiments support the concept that insulin stimulates small GC mitosis by activating PKC, which induces the expression of bothc-fosandc-jun. Both of these genes play essential roles in GC mitosis.
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胰岛素样生长因子 I 作为卵巢内调节剂：基本和临床意义
影响因子：
5.2
作者：
E. Adashi;C. Resnick;E. Hernández;A. Hurwitz;C. Roberts;D. Leroith;R. Rosenfeld
通讯作者：
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影响因子：
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作者：
M. A. Bley;J. Simon;A. Estevez;L. de Asúa;J. Barañao
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J. Barañao
核原癌基因的类固醇激素调节。
影响因子：
20.3
作者：
Schuchard,M;Landers,JP;Sandhu,NP;Spelsberg,TC
通讯作者：
Spelsberg,TC
大鼠颗粒细胞增殖的流式细胞荧光分析。
DOI：
--
发表时间：
1988
期刊：
Journal of Reproduction and Fertility
影响因子：
--
作者：
A. Hirshfield;G. Flickinger;Z. Ben
通讯作者：
Z. Ben
影响因子：
56.9
作者：
COOK, SJ;MCCORMICK, F
通讯作者：
MCCORMICK, F