奥曲肽对胰腺癌组织SST2R和SST2RmRNA表达的影响

目的探索SD大鼠胰腺癌组织SST2R及SST2R mRNA的表达以及外源性生长抑素类似物善得定治疗后其表达量的变化.方法采用二甲基苯丙蒽(DMBA)诱导鼠胰腺癌模型.将实验大鼠随机分为胰腺癌组(A组)、胰腺癌治疗组(B组)、模型制作后未形成胰腺癌的假阳性组(C组),以及正常大鼠组(D组).在善得定(10μg/kg,每6 h 1次)治疗前和治疗后的3 d、7 d、14 d,分别取各组胰腺组织标本.分别采用放射免疫法、逆转录聚合酶链法(RT-PCR)分析各组胰腺癌组织SST2R及SST2RmRNA的表达.结果A、B组SST2R及SST2R mRNA的表达比C、D组显著减少(P＜0.05),尤以善得定治疗后的B组减少更为明显,其与A组比较有显著性差异(P＜0.05).B组在治疗后3 d、7 d、14 d时相互比较无显著性差异(P＞0.05),但与其治疗前比较有显著性差异(P＜0.05).结论SD大鼠胰腺癌组织SST2R mRNA和SST2R的表达量明显减少;在善得定治疗后其表达量下降更为明显(P＜0.05).我们认为,胰腺癌组织SST2R mRNA表达量明显减少可能是导致SSTR表达量显著减少和外源性生长抑素类似物治疗临床胰腺癌效果不佳的主要原因之一.     

善得定治疗食管静脉曲张出血的临床对照研究

作者将71例肝硬化食管静脉曲张出血患者分为3组，分别用善得定，垂体后叶素及三腔管填塞治疗。结果：善得定的止血率为91．2％（31／34），平均止血时间25．5分，垂体后叶素止血率41．2％（7／17），平均止血时间37．1分，而三腔管填塞：90％（18／20），6小时。善得定组，垂体后叶素组和填塞组的平均输血量分别为566ml,918ml和550ml。此结果显示善得定在止血率，平均止血时间和平均输血量方面均优于垂体后叶素（P＜0．001）。善得定组的平均止血时间显著短于填塞组（P＜0．001），但在止血率与平均输血量方面与之无明显差异（P＜0．05）。此外，善得定的副反应轻微，观察中仅3例患者有恶心症状。所以，作者认为，善得定是治疗食管静脉曲张出血的最佳选择之一。     

人参调脾散对腹泻型肠易激综合征患者结肠黏膜5羟色胺3受体mRNA表达的影响

[目的]检测腹泻型肠易激综合征（IBS-D）患者结肠组织5羟色胺3受体mRNA（5-HT3RmRNA）的表达水平,探讨中药人参调脾散治疗IBS-D的作用机制。[方法]采用逆转录-聚合酶链式反应（RT-PCR）方法分析IBS-D患者治疗前后及正常人（对照组）乙状结肠黏膜5-HT3RmRNA表达水平的变化。[结果]mS-D患者治疗前5-HT3RmRNA表达水平较对照组显著增高,2组比较差异有统计学意义（P〈0．05）;经人参调脾散治疗后5-HT3RmRNA表达水平减低,与对照组比较差异无统计学意义（P〉O．05）;IBS-D患者治疗前后5-HT3RmRNA表达水平自身比较差异有统计学意义（P〈0．05）。[结论]人参调脾散能通过下调IBS-D患者结肠黏膜5-HT3RmRNA表达,降低5-HT3R活性,达到治疗IBS-D的作用。     

Runx3过表达对慢性乙型肝炎患者Th1、Th2型细胞因子表达的影响

目的：探讨 Runx3过表达对 CHB 患者 Th1、Th2型细胞因子表达水平的影响。方法重组慢病毒载体pGC-FU-Runx3与阴性对照慢病毒载体 pGC-FU 分别转染29例 CHB 患者外周血 CD4＋ T 细胞,收集培养3 d、5 d 和7 d的细胞培养上清液,应用 ELISA 检测 Th1型细胞因子 IFN-γ、IL-2和 Th2型细胞因子 IL-4、IL-10的表达水平。结果与pGC-FU 转染组比较,pGC-FU-Runx3转染组 Th1型细胞因子 IFN-γ的表达水平在3 d（P ＜0．05）、5 d（P ＜0．01）和7 d （P ＜0．01）时均明显升高;IL-2的表达水平在3 d 时差异无统计学意义（P ＞0．05）,但在5 d（P ＜0．05）和7 d（P ＜0．01）时均明显升高。与 pGC-FU 转染组比较,pGC-FU-Runx3转染组 Th2型细胞因子 IL-4的表达水平在3 d 时差异无统计学意义（P ＞0．05）,但在5 d（P ＜0．01）和7 d（P ＜0．05）时均明显降低;IL-10的表达水平在3 d 时差异无统计学意义（P ＞0．05）,但在5 d（P ＜0．05）和7 d（P ＜0．05）时均明显降低。与 pGC-FU 转染组比较,pGC-FU-Runx3转染组 IFN-γ／IL-4比值在3 d（P ＜0．01）、5 d（P ＜0．01）和7 d（P ＜0．01）时均明显增大。结论 Runx3过表达可以促进 CHB 患者 Th1型细胞因子的分泌,抑制 Th2型细胞因子的分泌,使其 Th1／Th2失平衡得到改善。     

螺内酯对2型糖尿病大鼠肾脏紧张素转换酶2和细胞间黏附分子表达的影响

目的观察螺内酯对T2DM大鼠肾脏紧张素转换酶2（ACE2）和细胞间黏附分子（ICAM-1）表达的影响,以探讨其对糖尿病肾脏病变的保护作用。方法用高脂高糖饲料喂养大鼠2个月后,腹腔注射30mg／kg STZ制备糖尿病大鼠模型,分为正常对照（NC）组、糖尿病（DM）组、螺内酯治疗（R）组,检测第16周FBG、Cr、24hUAER、肾重／体重（×10^-3）;并用免疫组化和RT-PCR的方法检测16周后大鼠肾脏ACE2和ICAM-1表达的改变。结果第16周末DM、R组各项比较,差异无统计学意义（P〉0．05）,但均高于NC组（P均〈0．01）;R组ACE2水平高于DM组（P〈0．01）,ICAM-1水平低于DM组（P〈0．05）。结论螺内酯通过增加肾脏组织ACE2的表达、降低ICAM-1的表达而发挥保护肾脏的作用。     

氯沙坦通过增加葡萄糖转运蛋白4膜转位改善2型糖尿病大鼠胰岛素抵抗

目的研究2型糖尿病（T2DM）sD大鼠血管紧张素Ⅱ受体拮抗剂（ARB）是否改善胰岛素抵抗及对IRSl磷酸化、P13K途径中Akt磷酸化及GLUT4转位的影响。方法42只sD大鼠分别给予高脂高糖饮食／链脲佐菌素（STZ）或普通饮食喂养,当空腹血糖（FPG）〉／7．8mmol／L且伴有胰岛素抵抗者为成模T2DM大鼠20只,正常组20只;分为正常不干预组（A组）、正常干预组（B组）、T2DM不干预组（C组）及T2DM干预组（D组）,每组10只。B组及D组给予氯沙坦（4mg·k～·d“）,干预6周后计算胰岛素敏感指数（ISI）,取腓肠肌备用。通过免疫组织化学（IHC）及Westernbloting检测IRSl／P＇yr_IRSl、Akt／Pser473-Akt及GLUT4蛋白表达。结果（1）成功制备了T2DM大鼠模型。IHC结果示C、D组较A、B组P”-IRSl、P-Akt蛋白表达减少;Westernbloting结果示Ptyr。-IRSl、GLUT4膜蛋白表达减少（P〈0．05）。（2）氯沙坦干预后,D组FBG（mmol／L）、FINS（p~U／M1）（18．8±4．1,27±5）较c组（19．74-3．7,27±6）降低,IsI升高（D组一6．18±0．08,C组一6．18±0．08,P〈0．05）;IHC示Ptyr-IRSl蛋白表达升高（P〈0．05）;Westernbloting示GLUT4膜蛋白、P-IRSl上升（P〈0．05）,P-Akt蛋白的表达无差异（P〉0．05）。结论氯沙坦通过增加骨骼肌组织中GLUT4的转位而改善T2DM大鼠的胰岛素抵抗。     

胰腺癌环氧合酶-2表达的意义

目的研究胰腺癌中COX-2表达的意义．方法应用免疫组化SP法检测82例胰腺癌、22例慢性胰腺炎、9例胰腺良性肿瘤、15例正常胰腺组织和2株人胰腺癌细胞中COX-2的表达,然后比较胰腺癌组织COX-2表达与胰腺癌患者临床病理特征的关系。结果2株人胰腺癌细胞COX-2表达均阳性。70．7％（58／82）胰腺癌组织可见COX-2表达,而正常胰腺组织只有6．7％（1／15）呈微弱表达。COX-2在4种组织中的表达程度有显著性差异（P〈0．001）。胰腺癌组织COX-2表达显著高于其他3种组织（P〈0．05）。胰腺癌组织COX-2表达水平的高低与胰腺癌的临床病理特征无关（P〉0．05）。结论COX-2蛋白的检测对胰腺癌的诊断及其与胰腺良性肿瘤、慢性胰腺炎的鉴别诊断有帮助。胰腺癌组织COX-2表达不能作为预测患者预后的指标。     

吡喹酮对血吸虫病肝纤维化小鼠肝组织Bcl-2和Bax表达的影响

目的观察吡喹酮（Praziquantel）治疗对血吸虫病肝纤维化小鼠肝组织中与凋亡相关基因Bcl-2和Bax表达的影响。方法建立小鼠血吸虫病肝纤维化模型。模型对照组不做治疗，吡喹酮治疗组按500mg／kg给药，1次／d，连用2d。10周后处死小鼠，取肝组织制片，免疫组化染色（SP法），观察小鼠肝组织中Bcl2和Bax的表达水平；HE染色观察肝组织的病理学变化。实验设正常小鼠对照。结果模型对照组和治疗组小鼠肝组织Bcl2、Bax表达水平较正常对照组显著增高（P〈0．01或P〈0．05）；治疗组Bcl-2水平显著高于模型对照组（P〈0．05），而Bax的表达水平2组间差异无显著性（P〉0．05）。结论吡喹酮可能通过促进Bcl-2表达，减少肝细胞的变性坏死，阻止血吸虫病肝纤维化的发生。     

单侧输尿管梗阻肾间质纤维化大鼠肾组织PHB1和 PHB2的表达及意义

目的：观察单侧输尿管梗阻（ UUO）肾间质纤维化（ RIF）大鼠肾组织PHB1和PHB2的表达,并探讨其意义。方法80只雄性6周龄Wistar大鼠随机分为模型组和假手术组各40只。模型组大鼠分离左侧输尿管后行双重结扎,假手术组只探查到肾包膜。于造模后第2周末和第4周末,每组各处死20只大鼠,取左侧肾组织进行肾脏病理学检查,并计算RIF指数;应用实时荧光定量PCR检测大鼠肾组织PHB1、PHB2、TGF-β1 mRNA;Western blot检测肾组织PHB1、PHB2、TGF-β1、Ⅳ型胶原（ Col-Ⅳ）和纤维连接蛋白（ FN）。结果与假手术组比较,模型组大鼠各时间点RIF指数增高,梗阻时间越长RIF指数越高,P均＜0．01;肾组织PHB1、PHB2 mRNA及蛋白表达均降低,梗阻时间越长表达水平越低,P均＜0．01;TGF-β1 mRNA及蛋白、Col-Ⅳ和FN蛋白表达均增高,P均＜0．01。肾组织PHB1蛋白表达与RIF指数、TGF-β1、Col-Ⅳ、FN呈负相关（ r分别为－0．86、－0．87、－0．70、－0．73,P均＜0．05）;PHB2蛋白表达与RIF指数、TGF-β1、Col-Ⅳ、FN呈负相关（r分别为－0．73、－0．81、－0．91、－0．84, P均＜0．05）;PHB1蛋白表达与PHB2蛋白表达呈正相关（ r＝0．78,P＜0．05）。结论在UUO所致RIF大鼠肾组织中,PHB1和PHB2表达显著降低,参与RIF的发生发展。     

脊髓损伤大鼠胃肠动力障碍及其可能机制

背景：胃动素（MTL）和生长抑素（SST）是对胃肠动力有兴奋和抑制作用的脑肠肽,在胃肠动力障碍中起重要作用。目的：研究脊髓损伤大鼠胃肠动力的变化及其可能的作用机制。方法：将138只大鼠随机分为模型组和对照组,采用重物坠落法建立脊髓损伤模型。造模后第1d,7d分别处死大鼠,行HE染色观察脊髓组织,并检测胃排空和小肠推进率。采用RT—PCR法检测MTL—R1A和SSTR：mRNA表达。结果：造模后第1d、7d,模型组脊髓组织形态学发生明显变化。造模第7d,与对照组相比,模型组胃内核素残留率明显增加（76．66％±11．84％对55．32％．4-10．88％,P〈0．01）,小肠推进率明显减少（31．64％±5．47％对43．56％±7．00％,P〈0．01）;MTL—R1AmRNA表达明显降低（0．21±0．07对0．47±0．13,P〈0．01）,SSTR2mRNA表达明显升高（1．12±0．21对0．62±0．13,P〈0．01）。结论：脊髓损伤后胃肠动力障碍的发生可能与胃组织MTL-R1ArnRNA表达下调以及结肠组织SSTR：mRNA表达匕调有关。     

Alteration of somatostatin receptor subtype 2 gene expression in pancreatic tumor angiogenesis

AIM: To explore the difference of somatostatin receptor subtype 2 (SST2R) gene expression in pancreatic cancerous tissue and its adjacent tissue, and the relationship between the change of SST2R gene expression and pancreatic tumor angiogenesis related genes. METHODS: The expressions of SST2R, DPC4, p53 and ras genes in cancer tissues of 40 patients with primary pancreatic cancer, and the expression of SST2R gene in its adjacent tissue were determined by immunohistochemiscal LSAB method and EnVision(TM) method. Chi-square test was used to analyze the difference in expression of SST2R in pancreatic cancer tissue and its adjacent tissue, and the correlation of SST2R gene expression with the expression of p53, ras and DPC4 genes. RESULTS: Of the tissue specimens from 40 patients with primary pancreatic cancer, 35 (87.5%) cancer tissues showed a negative expression of SST2R gene, whereas 34 (85%) a positive expression of SST2R gene in its adjacent tissues. Five (12.5%) cancer tissues and its adjacent tissues simultaneously expressed SST2R. The expression of SST2R gene was markedly higher in pancreatic tissues adjacent to cancer than in pancreatic cancer tissues (P<0.05). The expression rates of p53, ras and DPC4 genes were 50%, 60% and 72.5%, respectively. There was a significant negative correlation of SST2R with p53 and ras genes (chi(1)(2)=9.33, chi(2)(2)=15.43, P<0.01), but no significant correlation with DPC4 gene (chi(2)=2.08, P>0.05). CONCLUSION: There was a significant difference of SST2R gene expression in pancreatic cancer tissues and its adjacent tissues, which might be one cause for the different therapeutic effects of somatostatin and its analogs on pancreatic cancer patients. There were abnormal expressions of SST2R, DPC4, p53 and ras genes in pancreatic carcinogenesis, and moreover, the loss or decrease of SST2R gene expression was significantly negatively correlated with the overexpression of tumor angiogenesis correlated p53 and ras genes, suggesting that SST2R gene together with p53 and ras genes may participate in pancreatic cancerous angiogenesis.     

Hedgehog信号通路相关蛋白在大鼠胰腺癌发生过程中的变化

目的 观察Hedgehog信号通路相关蛋白Ptch、Smo和Gli1在胰腺癌发生过程中的作用。方法 200只SD大鼠分成对照组(20只)、二甲基苯并蒽(DMBA)组(90只)和环巴明治疗组(90只)。通过胰腺被膜下直接置入DMBA方法诱导胰腺癌模型。环巴明组在置人DMBA后每天腹腔注射6.25 ml/kg 体重环巴明溶液。4个月后处死大鼠,观察胰腺组织病理学改变,应用免疫组化SP法检测胰腺癌及正常胰腺组织中Ptch、Smo、Gli1的蛋白表达。结果 DMBA组胰腺癌诱发成功率为57.5％ (46/80),诱发的肿瘤最大径为0.5～＞2.0 cm;环巴明组诱发成功率为17.1％ (14/82),肿瘤最大径为0.5 ～2.0 cm。两组胰腺癌发生率及肿瘤大小的差异具有统计学意义(P值均＜0.05)。DMBA组胰腺癌组织中Ptch、Smo及Gli1阳性表达率分别为82.6％、73.9％和65.2％;环巴明组分别为50.0％、42.9％和28.6％,两组差异具有统计学意义(P值均＜0.05)。3组的正常胰腺组织中均无Ptch、Smo、Gli1阳性表达。结论 较大剂量DMBA置入胰实质内可在短期内获得较高的胰腺癌发生率;胰腺癌组织Hedgehog信号蛋白表达显著增加;环巴明能抑制Hedgehog信号蛋白表达,进而抑制胰腺癌发生和发展。     

Changes in somatostatin receptor expression of the pancreas and effectiveness of octreotide in rats with acute necrotizng pancreatitis

OBJECTIVE: To investigate changes in the expression of the somatostatin receptor (SSTR) of the pancreas and of pancreatic blood flow, and its relationship to the metabolism of eicosanoids in order to elucidate the effectiveness of octreotide, an analog of somatostatin, in acute necrotizing pancreatitis (ANP). METHODS: A model of ANP was induced in rats with injection of sodium taurocholate via the pancreaticobiliary duct. The SSTR was detected using a radioligand binding assay (RBA) with ¹²⁵I‐somatostatin‐14, and the SSTR2 mRNA of the pancreas was analyzed using in situ hybridization. Pancreatic blood flow and the metabolites of eicosanoids were also determined. RESULTS: The SSTR of the pancreas was 109.70 ± 58.32 fmol/mg protein in normal rats. A significant decrease in the SSTR, together with the signals of SSTR2 mRNA, was shown at 3, 6 and 12 h after onset of ANP. Pancreatic blood flow was reduced and thromboxin‐2 was increased significantly in the course of ANP. In the ANP group treated with octreotide, both the decrease in pancreatic blood flow and the abnormal metabolism of eicosanoids were corrected, and the pathological damage was relieved. CONCLUSION: SSTR expression of the pancreas is significantly reduced in ANP. Correction of the abnormal metabolism of eicosanoids and improvement in pancreatic microcirculation may be the major mechanism of somatostatin analogs in the treatment of ANP and inhibition of pancreatic enzymes via their receptors plays a minor role.     

生长抑素受体2转染胰腺癌细胞生物学行为的研究

目的探讨生长抑素受体2(SSTR2)对胰腺癌恶性行为的影响。方法利用原先已构建的腺病毒载体Adv-GFP-SST2R将人SSTR2全长cDNA转染导入胰腺癌细胞株PC3中,用RT-PCR检测SSTR2mRNA表达。通过肿瘤细胞与基膜成分黏附能力测定、运动能力测定、明胶酶谱法观察转染前后细胞的生物学特性的改变。结果转染Adv-GFP-SST2R的PC3细胞表达SST2RmRNA。SSTR2转染胰腺癌PC3细胞后,胰腺癌细胞与基质的黏附性、运动性下降,明胶酶的分泌能力明显减弱。结论SSTR2转染可明显减轻胰腺癌的恶性行为。     

The clinical response to somatostatin analogues in acromegaly correlates to the somatostatin receptor subtype 2a protein expression of the adenoma

Objective Reduced expression of the somatostatin receptor subtype 2 (SSTR2) has been suggested as an explanation for the poor response to octreotide in acromegaly, but studies correlating levels of SSTR2 mRNA to octreotide efficacy have been contradictory. Some studies have found better responses to somatostatin analogues in G‐protein α subunit (Gsα) mutation (gsp oncogene)‐positive adenomas. The aim of this study was to determine adenoma SSTR2a protein expression and gsp status in a large group of patients with acromegaly, and relate this to the clinical effect of octreotide. Patients Seventy‐one patients were included. All underwent transsphenoidal surgery, 23 patients after preoperative octreotide treatment. Measurements The adenoma SSTR2a expression was examined by immunohistochemistry and Western blot analysis, and gsp status determined. An acute octreotide test was performed, and the change in IGF‐1 level after 6 months preoperative octreotide treatment was recorded. Results The acute octreotide response in non‐pretreated patients and the preoperative long‐term octreotide response were significantly better in patients with adenomas containing a large proportion of cells that stained positively for SSTR2a by immunohistochemistry. However, the SSTR2a protein level assessed by Western blot did not correlate with the octreotide response. The preoperatively treated group had lower SSTR2a protein levels and fewer adenomas with a large percentage of positively stained cells. The gsp oncogene was detected in 43% of the adenomas but did not correlate to the octreotide response. Conclusion The clinical effect of octreotide correlates with the proportion of cells positive for SSTR2a in immunohistochemical staining, rather than the adenoma SSTR2a protein level. There may be a down‐regulation of SSTR2a during octreotide treatment.     

生长抑素类似物对急性胰腺炎胰腺组织转化生长因子β1基因改变的研究

目的：观察比较生长抑素类似物治疗大鼠急性胰腺炎前后胰腺组织转化生长因子β1（transforming growth factor β1,TGF-β1)的表达、DNA合成及总蛋白含量,并探讨其作用机制。方法：以雨蛙肽腹腔注射诱导大鼠急性胰腺炎模,并于生长抑制素类似物治疗前后6、24、48、72、96h处死大鼠。同时应用逆转录多聚酶链反应（RT－PCR）技术检测治疗前后胰腺组织TGF-β1mRNA表达,核素体外掺入法测定胰腺组织DNA合成及Lowry法测定胰朱组织总蛋白含量,结果：胰腺炎诱导后血清淀粉酶上升,生长抑素类似物治疗后显著下降,正常胰腺组织、胰腺炎诱导后6h,示见TGF-β1mRNA表达,TGF-β124h后出现表达,72h时达高峰。生长抑素类似物治疗后6h即可检测到TGF-β1表达,且24h、48h时表达均较非治疗组显著增强,并24h时达最大值。同时腺炎诱导后72h,DNA合成显著下降,治疗后96hDNA合成明显增加,胰腺炎诱导后48h总蛋白含量有明显增高,至96h达高峰。结论：生长抑素类似物治疗急性胰腺炎促进胰腺再生,再可能是通过诱导TGF-β1基因表达增强,促进多种细胞包基质成分的合成,增加强胰腺DNA合成和蛋白含量,从而加速胰腺组织的再生和修复。     

Characterization of the functional and growth properties of long-term cell cultures established from a human somatostatinoma

In somatostatinoma, a rare malignant somatostatin (SST)-secreting neoplasia, tumour regression is rarely observed, implying the need for novel antiproliferative strategies. Here, we characterized a long-term culture (SST-secreting cancer (SS-C cells)) established from a human somatostatinoma. High concentrations of SST and chromogranin A were released by SS-C cells and SST release was stimulated by depolarizing stimuli and inhibited by the SST analogue, octreotide. SS-C cells expressed mRNA for SST receptor (SSTR) subtypes 1, 2 and 4, being also able to bind native SST. Moreover, SS-C cells were positively stained with an antibody to SSTR2. SS-C cells also expressed interferon-gamma (IFN-gamma) receptor mRNA and measurable telomerase activity. Our findings indicate that in vitro exposure of SS-C cells to native SST-28, to octreotide, to IFN-gamma, or to 3'-azido-3'deoxythymidine (AZT), a telomerase inhibitor, results in inhibition of SS-C cell proliferation. Concomitant with growth inhibition, apoptosis was detected in SST-, octreotide-, IFN-gamma- or AZT-treated SS-C cell cultures. Taken together our results characterized native SST, SST analogues, IFN-gamma and a telomerase inhibitor as growth-inhibiting and proapoptotic stimuli in cultured human somatostatinoma cells. Based on these findings, the potential of SST analogues, IFN-gamma and AZT, alone or in combination, should be further explored in the medical treatment of somatostatinoma.     

Deficiency of somatostatin (SST) receptor type 5 (SSTR5) is associated with sexually dimorphic changes in the expression of SST and SST receptors in brain and pancreas

The actions of somatostatin (SST) are mediated through five somatostatin receptor subtypes, termed SSTR1-5. Although SSTRs commonly display an overlapping pattern of tissue distribution, subtype-selective responses have been shown to occur in the same tissue. In the present study, we have investigated the changes in SSTR subtypes at the cellular and molecular level in both the brain and the pancreatic islets of mice deficient in SSTR5 (SSTR5KO). Expression levels of insulin and glucagon were also determined in the pancreas of these mice. Semi-quantitative RT-PCR and Western blot analysis showed significant increases in the expression of SSTR2 and 3 with a corresponding reduction in SSTR4 in the brains of female SSTR5KOs, while no changes were observed in male KOs. Strikingly, SST mRNA and SST-like immunoreactivity (SST-LI) were reduced in the brain of male KO animals but not in their female counterparts. In male SSTR5KO islets, there was an increase in the number of cells immunoreactive for SSTR1-3, whereas in female islets only SSTR3 expression was increased. Pancreatic SST-LI and SST mRNA, as well as immunoreactivity for insulin were reduced in male but not in female KO mice. These data indicate that deficiency of SSTR5 leads to subtype-selective sexually dimorphic changes in the expression of both brain and pancreatic SSTRs.