Increased Proliferation but Decreased Steroidogenic Capacity in Leydig Cells from Mice Lacking Cyclin-Dependent Kinase Inhibitor 1B
Increased Proliferation but Decreased Steroidogenic Capacity in Leydig Cells from Mice Lacking Cyclin-Dependent Kinase Inhibitor 1B
复制标题
缺乏细胞周期蛋白依赖性激酶抑制剂 1B 的小鼠间质细胞增殖增加但类固醇生成能力降低
DOI：
10.1095/biolreprod.108.074229
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发表时间：
2009-06-01
影响因子：
3.6
通讯作者：
Ge, Ren-Shan
中科院分区：
文献类型：
--
作者：
Lin, Han;Hu, Guo-Xin;Ge, Ren-Shan
增殖细胞表达细胞周期蛋白，细胞周期调节蛋白，其调节细胞周期蛋白依赖性激酶（CDK）的活性。CDK的作用由特异性抑制剂CDK抑制剂（CDKI）调节，其由Cip/Kip和INK 4家族组成。Cip/Kip CDKI 1B（Cdkn 1b，编码蛋白CDKN 1B，也称为p27（kip 1））在发育中的Leydig细胞（LC）中的表达已被报道，但CDKN 1B在LC中的功能尚不清楚。本研究的目的是通过检查Cdkn 1b基因敲除（Cdkn 1b（-/-））小鼠中的这些参数来确定CDKN 1B对LC增殖和类固醇生成的影响。通过溴脱氧尿苷掺入来测量LC增殖。在Cdkn 1b（-/-）和Cdkn 1b（+/+）小鼠中比较睾丸睾酮水平、mRNA水平和类固醇生成酶的酶活性。Cdkn 1b（-/-）小鼠的LC标记指数为1.5% ± 60.2%，几乎是Cdkn 1b（+/+）对照小鼠的0.2% ± 0.08%的7倍（P < 0.001）。Cdkn 1b（-/-）小鼠每个睾丸的LC数量是Cdkn 1b（+/+）对照小鼠的2倍。然而，睾丸睾酮水平，类固醇生成急性调节蛋白（星星），胆固醇侧链裂解酶（Cyp 11 a1）和3 β-羟基类固醇脱氢酶6（Hsd 3b 6）的mRNA水平，以及它们各自的蛋白质，在Cdkn 1b（-/-）小鼠中显著较低。我们的结论是，CDKN 1B的缺陷增加LC增殖，但减少类固醇的生成。因此，CDKN 1B是LC发育和功能的重要调节因子。
Proliferating cells express cyclins, cell cycle regulatory proteins that regulate the activity of cyclin-dependent kinases (CDKs). The actions of CDKs are regulated by specific inhibitors, the CDK inhibitors (CDKIs), which are comprised of the Cip/Kip and INK4 families. Expression of the Cip/Kip CDKI 1B (Cdkn1b, encoding protein CDKN1B, also called p27(kip1)) in developing Leydig cells (LCs) has been reported, but the function of CDKN1B in LCs is unclear. The goal of the present study was to determine the effects of CDKN1B on LC proliferation and steroidogenesis by examining these parameters in Cdkn1b knockout (Cdkn1b(-/-)) mice. LC proliferation was measured by bromodeoxyuridine incorporation. Testicular testosterone levels, mRNA levels, and enzyme activities of steroidogenic enzymes were compared in Cdkn1b(-/-) and Cdkn1b(+/+) mice. The labeling index of LCs in Cdkn1b(-/-) mice was 1.5% +/- 6 0.2%, almost 7-fold higher than 0.2% +/- 0.08% (P < 0.001) in the Cdkn1b(+/+) control mice. LC number per testis in Cdkn1b(-/-) mice was 2-fold that seen in the Cdkn1b(+/+) control mice. However, testicular testosterone levels, mRNA levels of steroidogenic acute regulatory protein ( Star), cholesterol side-chain cleavage enzyme (Cyp11a1), and 3beta-hydroxtsteroid dehydrogenase 6 (Hsd3b6), and their respective proteins, were significantly lower in Cdkn1b(-/-) mice. We conclude that deficiency of CDKN1B increased LC proliferation, but decreased steroidogenesis. Thus, CDKN1B is an important regulator of LC development and function.