雌激素受体基因和长白猪繁殖性能相关研究

通过检测612头长白母猪共2 239窝ESR基因的PvuⅡ酶切多态性,分析了不同ESR基因型和长白母猪繁殖性状的相关,以确定ESR基因在猪育种应用的可能性.头胎母猪、第2胎母猪和3胎以上母猪的资料分开统计.群体中B等位基因的频率很低,但似然比检验结果显示群体的基因频率处于哈代-温伯格连锁平衡状态.第1胎BB基因型母猪的总产仔数显著高于AA型母猪(12.05±0.82 vs 10.19±0.24)(P＜0.05),但BB基因型母猪的初生仔猪重显著低于AA型母猪(1.23±0.07vs 1.42±0.02)(P＜0.05).第3胎以上资料合并,BB基因型母猪的总产仔数显著多于AA和AB基因型母猪(11.98±0.63 vs10.90±0.48/10.92±0.51)(P＜0.05),产活仔数显著高于AA型母猪(10.31±0.58 vs 9.43±0.45)(P＜0.05);AB基因型母猪初生仔猪重显著低于AA型母猪(1.44±0.04 vs 1.48±0.04)(P＜0.05).所有资料合并,BB基因型母猪的总产仔数极显著高于AB型母猪(11.63±0.52 VS 10.63±0.42)(P＜0.01),显著高于AA型母猪(11.63±0.52 vs 10.70±0.40)(P＜0.05);BB基因型母猪的产活仔数显著高于AB和AA基因型母猪(10.15±0.50 vs 9.33±0.39/9.41±0.41)(P＜0.05).其余情况下各基因型母猪间繁殖性状间差异不显著(P＞0.05).总之,BB基因型母猪的总产仔数和产活仔数优于其他基因型母猪,但仔猪初生重较低.ESR基因可以作为遗传标记,用于本群长白猪产仔数的选择.     

二花脸和大白猪的脂肪组织中GH-R、IGF-1和IGF-Ⅰ R基因表达的发育性变化

分别于出生当天、3、20、30、45、90、120、180日龄随机屠宰二花脸公、母猪各4头(30日龄仅有公猪),于20、30、90、120、180日龄随机屠宰大白猪公猪4头,采集背部皮下脂肪组织.用RT-PCR方法,以18S rRNA作内标,定量分析脂肪组织中生长激素受体(GH-R)、胰岛素样生长因子-1(IGF-1)及胰岛素样生长因子Ⅰ型受体(IGF-Ⅰ R)基因表达的发育性变化,并进行品种和性别间比较.结果表明:脂肪组织中GH-R mRNA的表达有明显的发育性变化及品种差异,二花脸母猪GH-R mRNA水平出生时较低,45日龄达到高峰,之后维持稳定;二花脸公猪GH-R mRNA水平在出生时较高,至45日龄达到最高值,之后显著下降,但总体上没有性别差异;大白猪公猪GH-R mRNA水平极显著低于二花脸公猪(P＜0.01).脂肪组织中IGF-1 mRNA的表达有明显的发育性变化及性别和品种差异,二花脸母猪显著低于公猪(P＜0.05),大白猪公猪极显著低于二花脸公猪(P＜0.01); 脂肪组织中IGF-Ⅰ R mRNA的表达有明显的发育性变化,但在总体上没有明显的性别和品种差异.结果提示:猪脂肪组织中GH-R、IGF-1和IGF-Ⅰ R的基因表达有特定的发育模式,IGF-1基因表达的品种差异可能正是两品种猪脂肪沉积规律不同的主要原因之一.     

雷州黑鸭FSHR和ESR1与繁殖性状关联分析

旨为探究产蛋基因FSHR和ESR1对雷州黑鸭的影响。采用荧光定量PCR对FSHR和ESR1在雷州黑鸭0-120 d的下丘脑-垂体-卵巢轴的表达规律进行研究,并通过PCR-SSCP对FSHR和ESR1的多态性与繁殖性状关联分析。结果表明,FSHR在0-90 d表达量总体呈稳定上升趋势,但在90-120 d下丘脑和垂体表达量略微下调,差异不显著(P0.05);ESR1表达量在0-120 d表达量总体呈上升趋势,但在90 d卵巢表达量出现波动,差异不显著(P0.05);FSHR的SNP(g.856937GA,g.922947AG)和ESR1的SNP(g.190744AG)与雷州黑鸭产蛋量显著相关(P0.05),但与雷州黑鸭蛋品质关联不显著。以上结果提示:FSHR和ESR1对雷州黑鸭早期性腺发育起着重要作用,且3个SNP位点均可作为雷州黑鸭重要的产蛋标记基因。     

猪下丘脑和垂体中生长激素受体、胰岛素样生长因子1型受体的发育性变化

GH和IGF-1可作用于垂体或/和下丘脑负反馈性地调节垂体GH的分泌,而这种负反馈作用必须通过下丘脑或垂体的GHR和IGF-1R来实现.为研究猪垂体GH分泌负反馈调节的发育性变化和品种特点,分别在0、3、20、30、90、120和180日龄随机选取纯种雄性二花脸猪和大白猪各4头,屠宰并取下丘脑及垂体,用相对定量RT-PCR分析下丘脑和垂体GHR和IGF-1R mRNA水平.结果表明下丘脑GHR mRNA表达呈明显的时序性变化,在0到120日龄期间呈逐渐上升趋势,180日龄时显著下降(P＜0.05),提示在快速生长期,GH负反馈调控机制逐渐加强.下丘脑GHR mRNA表达还表现明显的品种间差异,在0到180日龄期间大白猪均显著高于二花脸猪(P＜0.05);而垂体GHR mRNA表达相对稳定,品种和年龄间差异不显著,提示GH的负反馈作用位点可能主要在下丘脑.IGF-1R与GHR的表达发育模式不同.下丘脑IGF-IR mRNA的表达相对稳定,无显著的年龄、品种间差异;而在垂体,大白猪和二花脸猪IGF-1R mRNA水平在出生时均较高,随后显著下降(P＜0.05),20日龄后逐渐上升至90日龄的较高水平,随后再次下降.大白猪垂体IGF-1 mRNA表达在30日龄和90日龄时显著高于二花脸猪(P＜0.05),而180日龄时二花脸猪垂体IGF-1R mRNA水平却显著高于大白猪(P＜0.05).结果提示,IGF-1长环负反馈作用位点可能不在下丘脑,而主要在垂体.     

5个与猪产仔数相关基因的效应分析

为了比较不同基因对猪产仔数效应大小,在相同的大白 （158头）、长白 （224头）猪群中采用PCR-RFLP法进行了ESR、FSHβ、PRL、PRLR、NCOA1 5种与产仔数相关基因的基因型频率检测及不同基因型的总产仔数和产活仔数效应分析,结果表明,对相同母猪群产仔数影响效应最大的是PRLR和NCOA1基因,AA型比BB型母猪总产仔数高2.28~3.33头（P<0.01）,产活仔数高1.57~3.30头（P<0.01）,其次为ESR和FSHβ基因,BB型比AA型母猪总产仔数高0.55~1.18头（P<0.05,长白例外）,产活仔数高0.37~1.20头（P<0.05）。PRL基因对产仔数效应不显著。     

沉默Smad4基因表达抑制猪卵巢颗粒细胞增殖并使细胞G_1期阻滞

Smad4是TGF-β/Smad信号通路的核心下游信号分子.为探明Smad4基因对猪卵巢颗粒细胞增殖及细胞周期的影响,采用RNA干扰技术,设计并合成猪Smad4基因的靶向小分子干扰RNA,由LipofectamineTMRNAiMix介导转染体外培养的猪卵巢颗粒细胞.应用实时荧光定量PCR检测Smad4mRNA的干扰效果,应用MTT法、流式细胞术检测细胞增殖和细胞周期的变化,同时应用荧光定量PCR检测转染前后CyclinD1、CyclinB、CyclinA2、CDK1、CDK2、CDK4等周期相关基因的mRNA表达量的变化.实验结果显示,靶向猪Smad4的特异性siRNA序列对Smad4mRNA表达的抑制率为79.85%(P0.01);沉默Smad4可以显著抑制猪卵巢颗粒细胞增殖,并且改变细胞周期分布,G0/G1期细胞比例显著高于各对照组(P0.05),S期细胞比例显著低于各对照组(P0.05),细胞分裂被阻滞;转染36h后CyclinD1、CDK1的mRNA表达量显著低于对照组,CyclinA2、CDK2、CDK4极显著低于对照组,CyclinB差异不显著.综上所述,Smad4是影响猪卵巢颗粒细胞增殖及细胞周期进程的重要基因之一.     

室旁核注射胰高血糖素样肽-1对不同病程糖尿病大鼠胃排空的影响

目的:研究下丘脑室旁核(paraventricular nucleus,PVN)注射胰高血糖素样肽-1(GLP-1)对糖尿病早期大鼠胃排空的影响,并探讨其相关作用机制.方法:60只清洁级雄性Wistar大鼠随机分为正常对照组(NC组),糖尿病组(DM组),GLP-1干预组(GLP-1组),每组各20只,后两组腹腔注射链脲佐菌素(STZ)制备糖尿病模型,分别于注射STZ2周、6周后每组随机取半数进行实验,实验前于无菌条件下大鼠一侧下丘脑PVN区埋置套管,GLP-1组经套管注入GLP-1,NC组及DM组注入等体积生理盐水.酚红灌胃法检测胃排空率,酶联免疫吸附法(ELISA)测定血浆GLP-1浓度,半定量RT-PCR法测定胃窦、胃底GLP-1RmRNA表达.结果:注射STZ2周后,DM组较NC组胃排空率显著升高(P＜0.01).GLP-1组胃排空率低于DM组(P＜0.01),血浆GLP-1浓度高于DM组及NC组(P均＜0.05),胃窦GLP-1RmRNA表达明显高于DM组、NC组(P均＜0.01).注射STZ 6周后,DM组胃排空率高于NC组(P＜0.01).GLP-1组较DM组胃排空率显著降低(P＜0.01),血浆GLP-1浓度、胃窦GLP-1RmRNA表达显著高于DM组、NC组(P均＜0.01).结论:下丘脑PVN区注射GLP-1后,可减慢糖尿病大鼠初期加速的胃排空,原因可能与血浆GLP-1浓度及胃窦GLP-1RmRNA表达增加有关.     

HOXA10基因在多囊卵巢综合症患者卵巢中的表达

目的 探讨HOXA10基因在卵巢中颗粒细胞的表达及其与多囊卵巢综合征的关系.方法 采用逆转录聚合酶链反应及免疫印迹法分别测定25例多囊卵巢综合征(PCOS)妇女和32例卵巢功能正常(Non-PCOS)妇女卵巢黄素化颗粒细胞中HOXA10 mRNA和蛋白的表达水平.结果 PCOS妇女黄素化颗粒细胞中HOXA10 mRNA的表达和蛋白的表达均低于Non PCOS妇女(P＜0.01,P＜0.05).结论 HOXA10基因在卵巢中有表达,PCOS妇女卵巢黄素化颗粒细胞HOXA10 mRNA和蛋白表达水平明显低于Non-PCOS妇女,提示该基因可能参与了PCOS的发生及发展过程.     

右美托咪定对缺氧/复氧诱导的A549细胞凋亡及caspase-12表达的影响

本研究旨在探讨右美托咪定(dexmedetomidine,DEX)对缺氧/复氧(hypoxia/reoxygenation,H/R)诱导的A549细胞凋亡以及caspase-12表达的影响。取对数生长期的A549细胞,随机分为对照组、DEX组、H/R组和DEX+H/R组。对照组和DEX组细胞常氧培养30 h,H/R组和DEX+H/R组细胞缺氧6 h、复氧24 h建立H/R模型,其中DEX组和DEX+H/R组给予1 nmol/L DEX干预。造模结束后用倒置显微镜观察细胞形态学的变化;原位末端标记(TUNEL)法检测A549细胞的凋亡指数(apoptotic index,AI);CCK-8法检测A549细胞活力;caspase-3活性检测试剂盒检测各组caspase-3酶的活性;Western blot和RT-PCR分别检测A549细胞GRP78、caspase-12蛋白和mRNA的表达水平。结果显示,与对照组相比较,H/R组细胞发生融合现象,形态呈多边型改变,细胞活力明显降低(P0.01),凋亡细胞数增加,AI值升高(P0.01);caspase-3酶活性上升(P0.01);GRP78、caspase-12蛋白和m RNA表达显著上升(P0.01)。经DEX干预后,与H/R组相比较,DEX+H/R组细胞损伤减轻,细胞活力上调(P0.01);凋亡细胞数减少,AI值显著下降(P0.01),caspase-3酶活性显著下降(P0.01);caspase-12蛋白和mRNA表达下降(P0.01)。本研究结果表明,DEX对H/R损伤时的A549细胞具有一定的保护作用,其机制可能与其下调caspase-12的表达、抑制细胞凋亡有关。     

光周期对蛋鸡GnRH-I,GnRH-Ra mRNA表达和卵巢发育的影响

60只75日龄ISA褐蛋鸡随机分成长光组(LL)和短光组(SL),试验期70 d。短光组恒定光/暗:8 h/16h;长光组起始光/暗:8 h/16 h,每周增加0.5 h,最长光/暗达到13 h/11 h。分别于105和136日龄每组取6羽蛋鸡采样,观察光周期对蛋鸡GnRH-I mRNA,GnRH-Ra mRNA表达以及卵巢发育的影响。结果表明:136 d长光组GnRH-I mRNA表达的丰度显著高于短光组(P0.05),且极显著高于105 d长光组和短光组的表达(P0.01)。136 d短光组GnRH-Ra mRNA表达较105 d显著下降(P0.05),长光组GnRH-Ra mRNA的表达丰度显著高于短光组(P0.05)。136 d长光组的卵巢重、卵巢指数极显著高于短光组(P0.01)。以上说明,长光明显上调开产前蛋鸡下丘脑GnRH-I mRNA的表达,促进卵巢的发育;短光则明显下调垂体GnRH-Ra mRNA的表达,致使卵巢发育延缓。     

The Correlation of Reproduction-Related Gene Expression with Germ Cell Number in DM and PLL Gilts

In this study, the ovarian germ cell number was counted in 3-week-old Duroc × Meishan (DM, n=30) and PIC × (Landrace × Large White) (PLL, n=53) gilts, and the mRNA expression levels of four reproduction-related genes were investigated by quantitative RT-PCR. Correlation of germ cell number with the expression level of these genes was analyzed. Results showed that the germ cell number of DM was significantly higher than that of PLL gilts (P<0.01), although there was no significant difference between the ovarian weight of DM and PLL gilts (P=0.269). No significant correlation existed between germ cell number and ovarian weight in the two gilt groups (R=0.335, P=0.07; R=0.119, P=0.398, respectively). A significant correlation was found between the germ cell number and expression level of ESR and IGF1R mRNA in DM gilts (R=0.648, P<0.05; R=0.757, P<0.01, respectively), but the correlation between the germ cell number and expression level of FSHR and INHBA mRNA did not reach statistical significance. Significant correlation was found between the germ cell number and the expression level of ESR, FSHR, and IGF1R mRNA in PLL gilts (R=0.435, P<0.01; R=0.438, P<0.01; R=0.292, P<0.05, respectively), but not with INHBA mRNA in PLL gilts.     

IGF1和IGF1R在小鼠第一个毛囊生长周期皮肤的表达

毛囊生长周期中,真皮乳头和毛基质间的基质 上皮信号调控细胞的增殖和分化。多功能细胞调控因子胰岛素样生长因子1（IGF1)是该信号路径的成员之一。第1个毛囊生长周期决定着毛囊的正常生长和发育,但IGF1在此期的作用未见报道。实时荧光定量PCR结果显示,IGF1在生长期皮肤中的相对表达量最低,在退化期表达量最高,在静止期表达量又降低。与生长初期相比,IGF1在退化期和静止期的表达量呈差异极显著（P＜0.01）;胰岛素样生长因子1受体（IGF1R）在生长期皮肤中的相对表达量最高,在退化期表达量最低,而在静止期表达量又升高。与生长初期相比,IGF1R在退化期和静止期的表达量呈差异极显著（P＜0.01）。Western 印迹结果显示,IGF1和IGF1R蛋白在小鼠皮肤第1个毛囊生长周期各阶段的表达趋势分别与其mRNA的表达趋势一致;免疫组织化学结果表明,IGF1主要分布在小鼠表皮,而IGF1R免疫阳性在小鼠毛囊毛球部、内外根鞘和毛乳头均有分布。以上实验结果揭示,IGF1和IGF1R在小鼠皮肤第1个毛囊生长周期的各阶段的差异性表达,可能在毛囊生长周期各阶段的转化过程中参与了黑色素的形成。然而,IGF1和IGF1R表达趋势不一致,提示IGF1在小鼠皮肤中发挥作用时,并非只与IGF1R结合才能发挥作用。     

HBV感染者外周血PBMC中TLR4 mRNA与病毒载量的相关性研究

目的探讨乙型肝炎病毒感染者外周血PBMC中TLR mRNA与乙肝病毒复制的相关性。方法采用逆转录PCR检测外周血单个核细胞（PBMC）中TLR4 mRNA的含量,实时荧光定量Real Time PCR的方法检测HBV DNA,进行相关性分析。结果不同病毒载量组（〈1×103copies/μg DNA,1×103copies/μg DNA〈且〈1×105copies/μg DNA,〉1×105copies/μg DNA）TLR4 mRNA水平差异具有显著性（P〈0.01）,HBV病毒载量的对数值与TLR4 mRNA的含量存在负相关（r=-0.537,P〈0.01）。TLR4 mRNA的相对表达量与患者的ALT、AST呈正相关（r=0.608、r=0.659,P〈0.01）。结论HBV在患者体内复制活跃、病毒载量增高与外周血单个核细胞TLR4mRNA的表达下调有关。     

Cloning and expression levels of genes relating to the ovulation rate of the Yunling black goat

This study investigated the nucleotide sequences and tissue expression levels of genes relating to the ovulation rate in Yunling black goats, a famous Yunnan province, China, local breed with low fecundity. Five genes, FSHB, FSHR, BMP15, BMPR1B, and ESR2, were investigated; the complete cDNA sequences of these genes were 390, 2088, 1185, 1509, and 1585 bp, respectively, and compared with Boer goats (a more fecund breed), the sequence identities were 99%, 99%, 99%, 100%, and 99%, respectively. There were two base differences in FSHB and BMP15, four in FSHR, and three in ESR2. There were fewer follicles and oocytes in Yunling black goats than in Boer goats. Expression levels of FSHB, FSHR, and BMP15 genes in Yunling black goats were lower, and expression levels of BMPR1B and ESR2 genes were higher. Serum FSH content was lower in Yunling black goats, but serum estrogen content was higher. Protein expression levels of FSHR, BMP15, BMPR1B, and ESR2 in ovary and pituitary correlated positively with gene mRNA expression levels. In Yunling black goats, the mRNA expression levels of FSHB, FSHR, and BMP15 positively correlated with litter size, but those of BMPR1B and ESR2 correlated negatively. Together, base changes and variations in mRNA and protein expression levels of genes relating to the ovulation rate result in low fecundity in the Yunling black goat. Reduced BMP15 and FSHR levels may be related to the observed fewer oocytes and, consequently, fewer follicles.     

siRNA-mediated type 1 insulin-like growth factor receptor silencing induces chemosensitization of a human liver cancer cell line with mutant P53

Overexpression of type 1 insulin-like growth factor receptor (IGF1R) contributes to the progression and metastasis of liver cancer, implying that IGF1R gene is a suitable target of RNA interference (RNAi) for liver cancer therapy. To investigate the possible regulation of IGF1R by P53, we examined the level of IGF1R expression in liver cancer cell lines in response to adriamycin. Levels of IGF1R mRNA and protein in cell lines with wild-type P53 decreased dramatically after P53 induction, but no such reduction of IGF1R was observed in cell lines with mutated P53. Inhibition of wild-type P53 in HEPG2 cells by small interfering RNA (siRNA) significantly upregulated the expression of IGF1R. IGF1R inhibition by siRNA in Huh7 cells with mutated P53 significantly depressed cell proliferation. To investigate the sensitivity of cancer cells to adriamycin after inhibition of IGF1R, we depressed IGF1R expression using siRNA, and then added adriamycin at an IC50 dose. After a further 48 h incubation with adriamycin, proliferation was significantly depressed in the cells treated with siRNA targeting IGF1R, in comparison with siRNA targeting scramble. Furthermore, both TUNEL and pro-caspase-3 expression assay showed a significant increase in apoptosis after combined treatment with adriamycin and siRNA targeting IGF1R. Our results demonstrate that IGF1R is downregulated by P53, and that siRNA targeting of IGF1R increases liver cancer cells sensitivity to adriamycin and promotes apoptosis. siRNA targeting of IGF1R could be potentially useful for increasing sensitivity to anti-cancer drugs, especially in drug-resistant cells with mutated P53.     

Acute dietary restriction in heifers alters expression of genes regulating exposure and response to gonadotrophins and IGF in dominant follicles

Dietary restriction in growing cattle and severe negative energy balance in lactating cows have been associated with altered gonadotropin secretion, reduced follicle diameter, reduced circulating oestradiol concentrations and anovulation. Therefore, we hypothesised that acute dietary restriction would influence the fate and function of the dominant follicle by altering the expression for genes regulating gonadotrophin and IGF response in ovarian follicles. Newly selected dominant follicles were collected 7-8 days after prostaglandin F(2α) (PGF) administration from heifers (n=25) that were individually fed a diet supplying 1.2 maintenance (M; control, n=8) or 0.4 M (restricted, n=17) for a total duration of 18-19 days. Heifers within 0.4 M were ovulatory (n=11) or anovulatory (n=6) depending on whether the dominant follicle present at PGF ovulated or became atretic following luteolysis. Control animals were all ovulatory. Acute dietary restriction decreased IGF-I (P<0.001) and insulin (P<0.05) in circulation; oestradiol (P<0.01) and IGF-I (P<0.01) in follicular fluid; and mRNA for FSHR (P<0.01) in granulosa cells but increased mRNA for IGFBP2 (P<0.05) in theca cells of the newly selected dominant follicle. However, this only led to anovulation when dietary restriction also decreased mRNA for CYP19A1 (P<0.05), IGF2 (P<0.01) and IGF1R (P<0.05) in granulosa cells and LHCGR (P<0.05) in theca cells of follicles collected from heifers fed 0.4 M. These results suggest that the catabolic environment induced by dietary restriction may ultimately cause anovulation by reducing oestradiol synthesis, FSH-responsiveness and IGF signaling in granulosa, and LH-responsiveness in theca cells of dominant follicles.     

绵羊肌肉H-FABP和PPARγ基因表达的发育性变化及其对肌内脂肪含量的影响

选取不同日龄的雄性哈萨克羊和新疆细毛羊,屠宰后取背最长肌,用索氏抽提法检测肌内脂肪（Intamuscular fat,IMF）含量,用荧光实时定量PCR法检测心脏脂肪酸结合蛋白（heart fatty acid-binding protein,H-FABP）和过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptorγ,PPARγ）基因表达的发育性变化极其对IMF含量的影响.结果表明：（1）随着日龄的增加,IMF含量在雄性哈萨克羊中持续上升,且在各生长期间的差异显著（P＜0.05）,而在新疆细毛羊的各生长期间无显著差异（P＞0.05）.雄性哈萨克羊的IMF含量在30～90日龄间极显著高于新疆细毛羊（P＜0.01）;（2）雄性哈萨克羊肌肉H-FABP基因的表达量在2日龄时最高,30日龄时降到最低,然后持续上升,各日龄间差异显著（P＜0.05）.新疆细毛羊中的表达量在2日龄时也最高,然后持续下降,到90日龄时降到了最低点,然后上升,各日龄间差异也显著（P＜0.05）;（3）雄性哈萨克羊肌肉PPARγ基因的表达量随着日龄的增加而呈下降趋势,各日龄间差异显著（P＜0.05）;新疆细毛羊中的表达量在2～60日龄期间持续上升且各日龄间差异显著（P＜0.05）,但在90日龄时降到最低点,然后上升;（4）在哈萨克羊中,H-FABP基因在30～90日龄间的表达量与IMF含量的相关系数为0.737（P＜0.01）,而PPARγ基因在2-90日龄间的表达量与之的相关系数为-0.835（P＜0.01）.     

An activated human follicle-stimulating hormone (FSH) receptor stimulates FSH-like activity in gonadotropin-deficient transgenic mice

FSH mediates its testicular actions via a specific Sertoli cell G protein-coupled receptor. We created a novel transgenic model to investigate a mutant human FSH receptor (FSHR(+)) containing a single amino acid substitution (Asp567Gly) equivalent to activating mutations in related glycoprotein hormone receptors. To examine the ligand-independent gonadal actions of FSHR(+), the rat androgen-binding protein gene promoter was used to direct FSHR(+) transgene expression to Sertoli cells of gonadotropin-deficient hypogonadal (hpg) mice. Both normal and hpg mouse testes expressed FSHR(+) mRNA. Testis weights of transgenic FSHR(+) hpg mice were increased approximately 2-fold relative to hpg controls (P < 0.02) and contained mature Sertoli cells and postmeiotic germ cells absent in controls, revealing FSHR(+)-initiated autonomous FSH-like testicular activity. Isolated transgenic Sertoli cells had significantly higher basal ( approximately 2-fold) and FSH-stimulated ( approximately 50%) cAMP levels compared with controls, demonstrating constitutive signaling and cell-surface expression of FSHR(+), respectively. Transgenic FSHR(+) also elevated testosterone production in hpg testes, in the absence of circulating LH (or FSH), and it was not expressed functionally on steroidogenic cells, suggesting a paracrine effect mediated by Sertoli cells. The FSHR(+) response was additive with a maximal testosterone dose on hpg testicular development, demonstrating FSHR(+) activity independent of androgen-specific actions. The FSHR(+) response was male specific as ovarian expression of FSHR(+) had no effect on hpg ovary size. These findings reveal transgenic FSHR(+) stimulated a constitutive FSH-like Sertoli cell response in gonadotropin-deficient testes, and pathways that induced LH-independent testicular steroidogenesis. This novel transgenic paradigm provides a unique approach to investigate the in vivo actions of mutated activating gonadotropin receptors.