Leydig细胞分化增殖及其调控

Leydig细胞是睾丸组织中极其重要的体细胞,其分泌睾酮,对维持精子发生、刺激生殖器官发育等均有着重要的作用.本文就Leydig细胞分化增殖过程中的细胞分型及其调控机制作一综述.     

自噬信号因子P70S6K参与Cox7a2调控睾酮生成机制研究

目的:研究Cox7a2对TM3 Leydig细胞睾酮生成的影响以及涉及其中的自噬调控信号的作用。方法:构建Cox7a2荧光表达载体,转染TM3 Leydig细胞。ELISA测定睾酮水平,Western印迹检测Cox7a2对睾酮合成快速调节蛋白StAR表达和自噬调控因子P70S6K磷酸化水平的影响。结果:在TM3 Leydig细胞中,LH刺激能增加促进StAR蛋白表达,增加睾酮合成水平。Cox7a2在TM3小鼠睾丸Leydig细胞中抑制P70S6K磷酸化水平,降低StAR蛋白的表达,进而抑制LH诱导的睾酮合成。结论:Cox7a2通过抑制快速调节蛋白StAR的表达减少LH诱导的睾酮分泌,这至少和Cox7a2抑制自噬调控因子P70S6K有关。     

睾丸巨噬细胞与雄性生殖

睾丸生殖细胞包含有各种细胞,按主要功能来区分,主要分生精细胞和非生精细胞,在睾丸众多细胞中,睾丸巨噬细胞(Testicular Macrophages)作为一类非生精细胞,具有特殊功能,它除了对睾丸的内环境有免疫防御的功能,还具有分泌功能,对相邻细胞的发育、成熟等方面有重要调控作用.     

睾丸生精功能障碍的促生精治疗

正睾丸内精子的产生主要受生殖内分泌激素的调控,高浓度睾酮(Testosterone,T)的生精上皮及支持细胞环境是精子发生的必须条件。在生理情况下,下丘脑、垂体及睾丸的内分泌激素形成完整的反馈调控系统,促进和调控精子的发生、成熟[1]。睾丸生精功能障碍是指因各种原因导致睾丸内生精上皮(或生精组织)生精能力下降,生精细胞部分或全部发育阻滞,形成少精子或无精子,导致男性不育。目前临床对睾丸生精功能障碍的治疗方法主要包括药物治疗、手术治疗和辅助生殖。药物治疗在临床上被广泛使用,某些药物也确实     

雄性生殖道巨噬细胞研究进展

综述了近年来关于雄性生殖道内巨噬细胞的研究进展 ,及其在男性生殖生理及病理方面的作用 ,包括睾丸巨噬细胞与Leydig细胞、支持细胞、生精细胞及下丘脑 垂体 性腺轴的紧密联系和相互影响 ,巨噬细胞在免疫炎症中的形态和功能改变 ,以及对炎症进展的调节作用。从而进一步阐明了睾丸巨噬细胞在睾丸内复杂的免疫调节网络中起的重要作用及其在生精过程和睾丸生精微环境的稳定中所发挥的独特功能 ,为临床治疗提供理论依据     

Leydig细胞睾酮合成功能和自噬调控

Leydig细胞是睾丸间质细胞,主要功能是合成睾酮。睾酮被运输到身体各处的靶器官,通过与受体结合发挥重要的生理功能。自噬(Autophagy)是细胞通过溶酶体降解自身物质的方式,能及时清除细胞的不利物质,有利于细胞适应各种环境。在Leydig细胞中,存在自噬现象,对Leydig细胞合成功能发挥调控,但是具体机制和信号转导过程等都不是很清楚。下面,对Leydig细胞合成和自噬的调节研究现状作一综述。     

非酶糖基化终末产物抑制大鼠睾丸Leydig细胞睾酮的生成

目的:研究非酶糖基化终末产物受体(RAGE)在大鼠睾丸Leydig细胞上的表达及非酶糖基化终末产物(AGEs)对大鼠睾丸Leydig细胞睾酮合成的抑制作用。方法:原代培养大鼠睾丸Leydig细胞,RT-PCR和免疫荧光技术检测RACE在大鼠Leydig细胞上表达,不同浓度AGEs处理Leydig细胞(25、50、100、200μg/ml),ELISA法测定睾酮分泌量。结果:RT-PCR和免疫荧光结果表明RAGE在大鼠睾丸Leydig细胞上表达,不同浓度AGEs处理后,人绒毛膜促性腺激素(hCG)诱导的Leydig细胞睾酮合成量呈剂量浓度依赖性下降,与对照组相比,50、100、200μg/ml AGEs处理组差异显著(P0.01)。结论:大鼠Leydig细胞上存在RAGE受体,AGEs显著抑制原代培养大鼠Leydig细胞睾酮的分泌。     

趋化素样因子超家族在小鼠睾丸中的基因发育表达调控和蛋白表达定位

目的研究CKLFSF2小鼠同源序列cklfsf26基因在睾丸组织发育中的表达和定位,为其功能研究做出提示。方法利用RT-PCR方法检测cklfsf26基因在不同周龄小鼠睾丸组织中的表达情况；制备cklfsf2b多克隆抗体,利用免疫组织化学方法,检测cklfsf2b蛋白在小鼠睾丸组织中的表达定位。结果cklfsf2bmRNA在出生后第2周内出现,表达量逐渐增加,在成年前即达高峰并持续表达。cklfsf2b蛋白特异性的表达于睾丸Leydig细胞和Sertoli细胞,阳性信号均位于胞质内。结论cklfsf2b基因存在发育的表达调控,随着睾丸发育的日趋成熟,表达量逐渐增加：在Leydig细胞和Sertoli细胞的特异性表达表明其在睾酮合成和精子发生中均可能发挥作用,但其具体功能还需深入研究。     

衰老的Leydig细胞中睾酮合成降低的机制

睾酮是男性体内主要的雄激素。老年男性体内睾酮水平下降使机体呈现肌肉松弛、骨质疏松和性欲减退等衰老现象，这与睾酮合成减少及其分泌节律改变密切相关。除了。肾上腺皮质有少量分泌以外，睾酮主要由睾丸间质中的Leydig细胞生成。对于衰老Leydig细胞中睾酮合成减少的机制的研究已有不少报道，影响     

Indian hedgehog在软骨内成骨和骨关节炎中作用的研究进展

Hedgehog基因,最初是在研究果蝇的基因突变时发现的,该基因突变的果蝇胚胎酷似受惊刺猬,因此而得名。目前研究表明:在脊椎动物中存在音速豪猪蛋白(sonic hedgehog,Shh),沙漠豪猪蛋白(deserthedgehog,Dhh)和印度豪猪蛋白(Indian hedgehog,Ihh)三种Hedgehog蛋白亚型。其中Shh参与胚胎肢芽不对称性发育和中枢神经系统的发育过程;Dhh是生殖系统和外周神经系统发育过程中重要的调控因子;Ihh则在软骨内成骨和骨关节炎(OA)的发生发展中发挥着重要的作用。本文主要关注其在软骨内成骨和OA中对软骨细胞的作用。     

Hedgehog Signaling in Mammary Gland Development and Breast Cancer

The Hedgehog pathway is critical for many developmental processes, including the formation of several epidermal appendages. In the mammary gland strict regulation of the Hedgehog pathway is required for normal development. Alterations in Hedgehog signaling result in defects in both the embryonic and postnatal mammary gland. Activation of Hedgehog signaling either by mutation or misexpression of pathway members can lead to the development and/or progression of cancers in multiple organs. This review addresses the current understanding and controversies of Hedgehog signaling in mammary gland development and its potential role in promoting breast carcinogenesis and cancer progression.     

Control of mammalian kidney development by the Hedgehog signaling pathway

The kidney is the most common site of congenital malformations that result in impaired renal function. Yet, the molecular mechanisms that control renal malformations are poorly understood. The Hedgehog signaling pathway plays critical roles during mammalian organogenesis. Aberrant Hedgehog signaling results in severe congenital abnormalities, including renal malformations. Here, we review the current body of knowledge on Hedgehog signaling during renal morphogenesis and highlight the gaps in our understanding. Furthermore, we propose mechanisms by which Hedgehog signaling contributes to both normal and abnormal renal development.     

TGF-betas: their role in testicular function and Sertoli cell tight junction dynamics

Transforming growth factor-betas (TGF-betas) are known to regulate multiple physiological functions in the testis, which include spermatogenesis, Leydig cell steroidogenesis, extracellular matrix synthesis and testis development. More recent studies have shown that TGF-beta3 also regulates Sertoli cell tight junction (TJ) dynamics in vitro via the p38 mitogen-activated protein (MAP) kinase pathway, suggesting that this cytokine plays a crucial role in regulating the opening and closing of the blood-testis barrier (BTB). This in turn regulates the passage of pre-leptotene and leptotene spermatocytes across the BTB at stages VIII-XI of the seminiferous epithelial cycle. This review summarizes recent advances of studies on TGF-betas in the testis, highlighting their regulatory role in TJ dynamics.     

Notch signaling inhibition induces G0/G1 arrest in murine Leydig cells

As a highly evolutionarily conserved signaling pathway, Notch widely participates in cell‐fate decisions and the development of various tissues and organs. In male reproduction, research on the Notch signaling pathway has mainly concentrated on germ cells and Sertoli cells. Leydig cells are the primary producers of testosterone and play important roles in spermatogenesis and maintaining secondary sexual characteristics. In this study, we used TM3 cells, a murine adult Leydig cell line, to investigate the expression profiles of Notch receptors and ligands and observe the effect of Notch signaling on the proliferation of TM3 cells. We found that Notch 1–3 and the ligands Dll‐1 and Dll‐4 were expressed in TM3 cells, Notch 1–3 and the ligand Dll‐1 were expressed in testis interstitial Leydig cells, and Notch signaling inhibition suppressed the proliferation of TM3 cells and induced G0/G1 arrest. Inhibition of Notch signaling increased the expression of p21^Waf1/Cip1 and p27. Overall, our results suggest that Notch inhibition suppresses the proliferation of TM3 cells and P21^Waf1/Cip1, and p27 may contribute to this process.     

Changes in the expression of claudins and transepithelial electrical resistance of mouse Sertoli cells by Leydig cell coculture

In the testis, tight junctions (TJs) between adjacent Sertoli cells are important for the formation of blood-testis barrier (BTB). To verify the role of paracrine interactions between the Sertoli and Leydig cells in the structure and function of BTB in testis, the expression of claudin-1 and -11, and transepithelial electrical resistance (TER) of the mouse Sertoli cells were examined under the Leydig cell coculture. TER of Sertoli cell monolayer was significantly larger under the Leydig cell coculture in comparison with the control culture. Meanwhile, the expression of claudin-1 slightly decreased and claudin-11 significantly increased in the Sertoli cells in the Leydig cell coculture compared with control. Testosterone significantly increased claudin-11 expression in cultured Sertoli cells. Taken together, it suggested that Leydig cell coculture changed the structure and functions of inter-Sertoli TJs in vitro. Interactions between Leydig and Sertoli cells might be involved in the development of functional blood testis barrier in mouse testis.     

Hedgehog信号传导通路相关基因在肝癌组织中的表达研究

目的 研究Hedgehog信号传导通路相关基因在肝癌组织中的表达,及其抑制剂对肿瘤细胞生长的影响.方法 免疫组化法检测14例肝癌组织切片、4个肝癌细胞系和正常肝细胞中Hedgehog信号传导通路成员Ihh、Ptch、Smo、Gli的蛋白表达;Western blot检测9例新鲜肝癌组织标本、6例正常肝组织标本和肝癌细胞系中Ihh、Ptch、Smo、Gh的蛋白表达;RT-PCR检测3肝癌组织标本和肝癌细胞系中Ihh、Ptch、Smo、Gli、Hip mRNA表达.结果 14例肝癌组织中免疫组化染色阳性的Gli 6例(42.9%),Ptch 10例(71.4%),Ihh 10例(71.4%),Smo 12例(85.7%).Western blot和RT-PCR检测显示,肿瘤组织中Gli基因的mRNA和蛋白表达均高于正常肝脏细胞,Hip基因的mRNA表达低于正常肝细胞.肝癌细胞系HepG2,Bel-7402和QGY-7701免疫细胞化学染色Pteh和Gli同时为阳性,证明为Hedgehog通路活化的细胞系.在环耙明(KAAD-cyclopamine)作用后,3个细胞系Ptch及Gli基因的mRNA表达下调(Ptch基因tHepG2=3.78,tBel-7402=9.03,tQGY-7701=5.63,Gli基因tHepG2=9.61,tBel-7402=4.15,tQGY-7701=20.30,均P＜0.05);QGY-7701组Hip基因RNA表达上调(t=4.70,P＜0.05).环耙明抑制肝癌细胞系QGY-7701的作用最明显.结论 原发性肝癌组织中Hedgehog信号传导通路有多种基因表达,环耙明有抑制肝癌细胞生长的作用.     

Inhibition of tyrosine kinases PDGFR and C-Kit by imatinib mesylate interferes with postnatal testicular development in the rat

The tyrosine kinase receptor c-kit and its interaction with the ligand, stem cell factor (SCF), play an essential role in the developing testis. C-kit is important for the development of the Leydig cells and for the migration, proliferation and survival of spermatogonia. Platelet-derived growth factor (PDGF) and its tyrosine kinase receptor (PDGFR) are important for the development of Leydig cells and myoid cells. The chemotherapeutic agent, imatinib mesylate (STI571, Glivec; Novartis) inhibits both of these tyrosine kinase receptors. Three-day treatment of immature male rats (SD) with imatinib (150 mg/kg) on postnatal days 5-7 delayed the formation of germ-line stem cell pool, reduced proliferation of type A spermatogonia and induced germ cell apoptosis. PDGFR-mediated proliferation of mesenchymal myoid precursors was also decreased and the length of the seminiferous cord was reduced. However, at the age of 11 weeks the exposed animals had normal epididymal sperm counts, whereas plasma levels of luteinizing hormone and follicle stimulating hormone were significantly increased. Imatinib serves as a good tool to study postnatal formation of the male germ-line stem cell pool and factors determining the final testicular size. As development of the human testis is controlled by the same mechanisms, further studies with primate and human models are needed to explore whether imatinib affects the testis in children as well.     

Hedgehog信号通路与骨质疏松症

Hedgehog信号通路是一条保守而重要的信号通路,涉及到多种细胞的增殖和分化活动。近年研究发现,Hedgehog信号通路可以通过上调Runx2和Osx等主要转录因子的表达促进间充质干细胞（mesenchymalstemcells,MSCs）向成骨细胞分化,并且抑制MSCs向脂肪细胞分化。Hedgehog信号通路还可以通过调节细胞周期蛋白促进成骨细胞增殖。本文综述总结了Hedgehog信号通路调节成骨细胞增殖分化的作用机制,认为Hedgehog信号通路通过促进成骨细胞增殖分化参与调节骨代谢,为骨质疏松症的治疗提供一种新思路。