Down‐modulation of keratin 8 phosphorylation levels by PRL‐3 contributes to colorectal carcinoma progression

Phosphatase of regenerating liver‐3 (PRL‐3) is a member of the PRL protein tyrosine phosphatase family and has been proposed to promote the invasiveness and metastastic capability of colorectal cancers (CRCs); however, the underlying mechanisms and target molecules of PRL‐3 protein remain unknown. On the basis of the biological significance of PRL‐3 phosphatase activity confirmed by the catalytically inactive PRL‐3 mutant (C104S) and a PRL‐3 inhibitor in CRC‐derived SW480 cells, we performed protein expression profiling to search for PRL‐3‐mediated effector proteins. By a comparative study of phosphorylated proteins that differentially expressed in wild type and C104S mutant PRL‐3‐transfected SW480 cells; the cytoskeletal intermediate filament keratin 8 (KRT8) was identified as a physiological PRL‐3‐interacting protein. Indeed, treatment with the PRL‐3 inhibitor effectively suppressed the phosphorylation of KRT8 at S73 and S431. Moreover, we detected the physiological interaction between PRL‐3 and KRT8 and their colocalization at cellular lamellipodias and ruffles in vivo. In CRC tissue samples, tumor cells with high PRL‐3 expression showed reduction or loss of phosphorylated KRT8 expression, particularly at the invasive front and in the liver metastases. In conclusion, our results indicate that PRL‐3 may play an important role for the promotion of CRC cell migration and metastatic potential through direct KRT8 dephosphorylation. © 2008 Wiley‐Liss, Inc.     

子宫肌瘤患者及接受UAE治疗后血清性激素水平分析

目的：探讨性激素在子宫肌瘤发病中的意义。方法：采用化学发光技术检测正常对照61例(对照组)、子宫肌瘤患6l例(患组)以及44例子宫肌瘤接受子宫动脉栓塞治疗(UAE)后的患，血清促卯泡成熟激素(FSH)、促黄体生成激素(LH)、雌激素(E2)、垂体泌乳素(PRL)、睾酮(T)水平。结果：子宫肌瘤患组的血清FSH、LH、PRL、T水平均明显高于对照组；血清E2水平与对照组无显差异。其中44例接受UAE治疗的子宫肌瘤患术后血清LH、E2、PRL、T水平均比术前明显降低，FSH与术前无显差异；术后血清FSH、PRL、T水平均明显高于对照组，LH、E2水平明显低于对照组。结论：PRL、T是子宫肌瘤的发病因素。     

前列腺癌患者血清IGF-I、PRL及SE-cad测定的临床意义

目的：探讨前列腺癌患者血清IGF-Ⅰ、PRL及SE-cad水平的变化及临床意义。方法：血清IGF-Ⅰ采用放射免疫分析;fPSA及PRL采用化学发光法;血清SE-cad采用酶联免疫分析法。结果：前列腺增生组患者血清IGF-Ⅰ水平较对照组升高显著（P〈0.05）;血清PRL含量也较对照组显著升高（P〈0.05）;SE-cad浓度其测定数值也存在显著性差异（P〈0.05）。而前列腺癌患者组血清IGF-Ⅰ水平较对照组升高更为显著（P〈0.01）;血清PRL含量也较对照组升高极其显著（P〈0.01）;SE-cad浓度其测定数值升高同样非常显著（P〈0.01）。灵敏度分析表明,fPSA＋IGF-Ⅰ和fPSA＋SE-cad两组灵敏度显著高于fPSA单项测定组;fPSA＋PRL组灵敏度略低,但P〉0.05。特异性分析则fPSA＋SE-cad组fPSA单项测定组显著增高（P〈0.05）,fP-SA＋PRL降低明显,fPSA＋IGF-Ⅰ组与单项组差异并不显著（P〉0.05）。结论：血清IGF-Ⅰ、PRL及SE-cad水平的变化与前列腺癌的发生关系密切,与fPSA的联合测定可提高诊断的灵敏度及特异性,有助于前列腺癌的辅助诊断。     

磁分离酶联免疫测定男性生殖激素方法性能评价

目的：对磁分离酶联免疫测定（MAIA）法测定男性生殖激素的方法学性能作临床和实验室评价。方法：将本法与放射免疫测定（RIA）法进行对比研究。结果：MAIA法测定促卵泡生成激素（FSH）、促黄体生成素（LH）、睾酮（T）和催乳素（PRL）的线性分别为0－150IU／L、0－200IU／L、0．5－55ng/L、0－250ng/L；最小检测量分别为0．3mIU/ml、0．25mIU/ml、4μIU/ml、4μIU/ml；批内CV＜4％，批间CV＜8％，平均回收率偏差＜5％，互感率＜3％；与RIA法比较，两法相关系数分别为0．9826、0．8550、0．8512、0．9831。临床质控观察60d，质控稳定；成年健康男性（n=95）血清FSH、LH、T、PRL的参考范围分别为：0．25－10．18IU／L、0．33－8．95IU／L、0．54－11．11ng/L和8．77－33．43ng/L。结论：用MAIA法测定男性生殖激素，方法灵敏，结果可靠，先例临床要求。     

急性精神分裂症中枢5-HT功能状态的研究

目的：探讨急性精神分裂症中枢5-HT的功能状态，并了解与临床症状间的关系。方法：通过帕罗西汀激发实验，以催乳素（PRL）作为应答指标；精神症状采用阳性和阴性综合征量表（PANSS）进行评定。结果：（1）急性组PRL基础水平符合正态分布，且明显低于慢性对照组，与健康对照组比较无显差异。（2）急性组激发后的PRL含量虽有增高趋势，但缺乏显意义；与慢性和健康两个对照组比较，均有显差异。（3）急性组PRL水平、AUC（曲线下面积）以及激发反应值与PANSS多介无明显相关关系。结论：与慢性精神分裂症相比，急性精神分裂症中枢5-HT的功能可能更加亢进；但与精神症状之间尚缺乏明显的相关关系。     

垂宁方治疗泌乳素型垂体瘤的临床疗效观察

【摘要】 目的 探讨垂宁方治疗泌乳素(PRL)型垂体腺瘤的临床疗效,为临床应用提供借鉴依据。方法 将2014年1月至2015年1月收治的60例PRL型垂体瘤随机分为A组、B组和C组。A组患者采用垂宁方进行治疗,B组患者采用溴隐亭进行治疗,C组患者采用溴隐亭联合垂宁方进行治疗;治疗6个月及1年时对患者的瘤体积、血清PRL水平及中医症候积分量表得分进行对比评价。结果 治疗6个月及1年时C组患者肿瘤大小改善情况明显优于A组和B组,差异有统计学意义（P<0.05）;治疗后3组患者血清PRL水平均显著降低（P<0.05）,C组血清中PRL水平改善程度显著高于其余两组（P<0.05）,且开始治疗后C组患者PRL水平均明显低于A组和B组,差异具有统计学意义（P<0.05）;经治疗后C组患者中医证候评价结果明显优于其余两组,差异具有统计学意义（P<0.05）。结论 垂宁方治疗PRL型垂体瘤具有理想的治疗效果,可有效抑制瘤体生长,降低患者血清中泌乳素水平,改善患者预后。     

服棉酚者和其他原因所致的无精症患者血中促性腺激素与甾体激素的变化

本文比较了正常男子(Ⅰ组)、各种无精症患者(包括棉酚服用者。Ⅱ组)、原因不明的无精症者(Ⅲ组)以及Klinefelter 综合征患者(Ⅳ)血浆中FSH、LH、PRL、T、E_2和F 的变化。结果所有无精症患者的平均FSH、LH 水平明显高于Ⅰ组(P<0.001),但PRL、T、E_2及F 的平均值与Ⅰ组无区别(P>0.05)Ⅱ、Ⅲ组患者FSH 水平升高者与正常者各为50%,其余各组明显高于正常。Ⅲ组的LH 及T/LH 比值仍在正常范围内,但T、E_2及F 的平均值升高,PRL 降低;其余各组LH 与FSH 平行升高,T 及T/LH比值明显低于Ⅰ组(P<0.001),但E_2、F 及PRL 则在正常范围内。本实验证实,避孕剂量的棉酚并不损害睾丸合成T 的功能。FSH 过高说明生精上皮损害过度。本文还提出了一些控制棉酚用量的客观指标。     

A new key neurohormone controlling reproduction,gonadotropin-inhibitory hormone (GnIH): Biosynthesis,mode of action and functional significance

Identification of novel neurohormones that play important roles in the regulation of pituitary function is essential for the progress of neurobiology. The decapeptide gonadotropin-releasing hormone (GnRH) is the primary factor responsible for the hypothalamic control of gonadotropin secretion. Gonadal sex steroids and inhibin inhibit gonadotropin secretion via feedback from the gonads, but a neuropeptide inhibitor of gonadotropin secretion was, until recently, unknown in vertebrates. In 2000, a novel hypothalamic dodecapeptide that inhibits gonadotropin release was identified in quail and termed gonadotropin-inhibitory hormone (GnIH). This was the first demonstration of a hypothalamic neuropeptide inhibiting gonadotropin release in any vertebrate. GnIH acts on the pituitary and GnRH neurons in the hypothalamus via a novel G protein-coupled receptor for GnIH to inhibit gonadal development and maintenance by decreasing gonadotropin release and synthesis. GnIH neurons express the melatonin receptor and melatonin stimulates the expression of GnIH. Because GnIH exists and functions in several avian species, GnIH is considered to be a new key neurohormone controlling avian reproduction. From a broader perspective, subsequently the presence of GnIH homologous peptides has been demonstrated in other vertebrates. Mammalian GnIH homologous peptides also act to inhibit reproduction by decreasing gonadotropin release in several mammalian species. Thus, the discovery of GnIH has opened the door to a new research field in reproductive neurobiology. This review summarizes the advances made in our understanding of the biosynthesis, mode of action and functional significance of GnIH, a newly discovered key neurohormone, and its homologous peptides.