We have previously shown a critical role of prolactin (PRL) during maturation and anti-tumor effects of murine natural killer (NK) cells in vitro and in vivo. We extended that study by exploring the ability of human N...We have previously shown a critical role of prolactin (PRL) during maturation and anti-tumor effects of murine natural killer (NK) cells in vitro and in vivo. We extended that study by exploring the ability of human NK cell lines (NK-92 and YT cell) to express PRL receptor (PRL-R) and to respond to PRL stimulation in vitro. Both human NK cell lines constitutively expressed PRL-R on membrane and mRNA transcripts,NK-92 cells contained higher level of PRL-R than YT cells,which correlated to the enhanced capacity of the cells to proliferate and to lyse target cells in response to PRL stimulation in the presence of trace amount of IL-2 or IL-15 in vitro. Two differences between IL-2 and IL-15 in functioning on human NK cells were for the first time observed. PRL synergized with IL-15 to improve proliferation of NK cells in a dose-dependent manner without double peak manifesting like IL-2. Although PRL enhanced the cytotoxicity of IL-2 or IL- 15 activated NK cells,it exerted the function through up-regulating gene expression of perforin without influence of FasL in IL-2-stimulated NK cells,while in IL-15-stimulated NK cells,PRL did the function through up-regulating gene expression of both perforin and FasL but not IFNγ. PRL increased expressions of IL-2Rα on membrane and of IL-2 mRNA in cells,indicating that PRL up-regulated NK cell function by improving positive feedback between IL-2 and IL-2R. The similar results were also observed in network between IL-15 and IL-15R. These data indicate a potential role of PRL in human NK cell modulation.展开更多
Experimental data shows that the binding of human prolactin(hPRL)to human prolactin receptor(hPRLr-ECD)is strongly pH-dependent,while the binding of the same receptor to human growth hormone(hGH)is pH-independent.Here...Experimental data shows that the binding of human prolactin(hPRL)to human prolactin receptor(hPRLr-ECD)is strongly pH-dependent,while the binding of the same receptor to human growth hormone(hGH)is pH-independent.Here we carry in silico analysis of the molecular effects causing such a difference and reveal the role of individual amino acids.It is shown that the computational modeling correctly predicts experimentally determined pKa’s of histidine residues in an unbound state in the majority of the cases and the pH-dependence of the binding free energy.Structural analysis carried in conjunction with calculated pH-dependence of the binding revealed that the main reason for pH-dependence of the binding of hPRL-hPRLr-ECD is a number of salt-bridges across the interface of the complex,while no salt-bridges are formed in the hGH-hPRlr-ECD.Specifically,most of the salt-bridges involve histidine residues and this is the reason for the pH-dependence across a physiological range of pH.The analysis not only revealed the molecular mechanism of the pH-dependence of the hPRL-hPRLr-ECD,but also provided critical insight into the underlying physicchemical mechanism.展开更多
Prolactin is a polypeptide hormone associated with an extensive variety of biological functions.Among the roles of prolactin in vertebrates,some were preserved throughout evolution.This is the case of its function in ...Prolactin is a polypeptide hormone associated with an extensive variety of biological functions.Among the roles of prolactin in vertebrates,some were preserved throughout evolution.This is the case of its function in the brain,where prolactin receptors,are expressed in different structures of the central nervous system.In the brain,prolactin actions are principally associated with reproduction and parental behavior,and involves the modulation of adult neurogenesis,neuroprotection,and neuroplasticity,especially during pregnancy,thereby preparing the brain to parenthood.Prolactin is mainly produced by specialized cells in the anterior pituitary gland.However,during vertebrate evolution many other extrapituitary tissues do also produce prolactin,like the immune system,endothelial cells,reproductive structures and in several regions of the brain.This review summarizes the relevance of prolactin for brain function,the sources of prolactin in the central nervous system,as well as its local production and secretion.A highlight on the impact of prolactin in human neurological diseases is also provided.展开更多
This study aimed to investigate the correlations among androgen receptor （AR） CAG repeat polymorphism, sex hormones and penile length in healthy Chinese young adult men. Two hundred and fifty-three healthy men （age...This study aimed to investigate the correlations among androgen receptor （AR） CAG repeat polymorphism, sex hormones and penile length in healthy Chinese young adult men. Two hundred and fifty-three healthy men （aged 22.8 ± 3.1years） were enrolled. The individuals were grouped as CAG short （CAGs） if they harbored repeat length of 〈20 or as CAG long （CAGL） if their CAG repeat length was 〉20. Body height/weight, penile length and other parameters were examined and recorded by the specified physicians; CAG repeat polymorphism was determined by the polymerase chain reaction （PCR） method; and the serum levels of the sex hormones were detected by radioimmunoassay. Student＇s t-test or linear regression analysis was used to assess the associations among AR CAG repeat polymorphism, sex hormones and penile length. This investigation showed that the serum total testosterone （T） level was positively associated with the AR CAG repeat length （P = 0.01）; whereas, no significant correlation of T or AR CAG repeat polymorphism with the penile length was found （P = 0.593）. Interestingly, an inverse association was observed between serum prolactin （PRL） levels and penile length by linear regression analyses （β = -0.024, P = 0.039, 95% confidence interval （CI）： -0.047, 0）. Collectively, this study provides the first evidence that serum PRL, but not T or AR CAG repeat polymorphism, is correlated with penile length in the Han adult population from northwestern China.展开更多
Today there is significant information indicating an effect of prolactin on the prostate gland. It has been shown to be involved in mechanisms leading to the synthesis of some proteins such as PSA and cathepsin D, syn...Today there is significant information indicating an effect of prolactin on the prostate gland. It has been shown to be involved in mechanisms leading to the synthesis of some proteins such as PSA and cathepsin D, synthesis of citrate and accumulation of zinc. Also, at the behavioral level, prolactin is known to control some aspects of reproduction, including documentation on the physiology of the prostate and the possibility to trigger pathologies in this sex gland. Although the later still is not clear, there is a correlation between the level of prolactin and the presence of prostate pathologies. Thus, the aim of this review is to show how prolactin is involved in the progression of some pathologies of this male sexual gland.展开更多
目的比较阿立哌唑与利培酮治疗女性首发精神分裂症患者的疗效和血浆催乳素水平变化及其与多巴胺D3受体(DRD3)基因Ser9Gly(rs6280)多态性的关联。方法选择完成8周阿立哌唑或利培酮治疗的女性首发精神分裂症患者各60例,于治疗前和治疗8周...目的比较阿立哌唑与利培酮治疗女性首发精神分裂症患者的疗效和血浆催乳素水平变化及其与多巴胺D3受体(DRD3)基因Ser9Gly(rs6280)多态性的关联。方法选择完成8周阿立哌唑或利培酮治疗的女性首发精神分裂症患者各60例,于治疗前和治疗8周后分别评测阳性与阴性症状量表(positive and negativesymptom scale,PANSS)。采用放射免疫法检测血浆催乳素水平,DNA测序技术检测DRD3基因Ser9Gly多态性,分析DRD3基因Ser9Gly多态性与两药疗效及血浆催乳素变化的关联。结果治疗8周后,两组PANSS减分率的差异无统计学意义[(59.79±23.48)vs.(63.30±22.66),P>0.05],但利培酮组血浆催乳素的变化值高于阿立哌唑组[(26.92±9.48)vs.(-25.25±8.07),P<0.05]。利培酮组中C等位基因携带者的血浆催乳素的增加明显高于未携带者[(52.48±27.01)ng/mL vs(36.07±17.46),P<0.05];而阿立哌唑组中未见此差异[(-23.27±8.36)vs.TT(-26.05±8.11),P>0.05]。两组8周后PANSS减分率(%)与DRD3基因Ser9Gly的差异均无统计学意义:阿立哌唑组[CC+CT(57.83±19.94)vs.TT(56.84±18.46),P>0.05];利培酮组[CC+CT(53.94±21.08)vs.TT(60.38±19.37),P>0.05]。结论阿立哌唑治疗女性首发精神分裂症疗效与利培酮相当,但引起血浆催乳素水平变化的幅度较小;利培酮引起血浆催乳素水平增加可能与DRD3基因Ser9Gly多态性有关联。展开更多
基金supported partly by Outstanding Young Scientist Award and Key Project by Natural Science Foundation of China(No.30125038,No.30230340)The Major Sate Basic research Development program of China(No.2001CB510009)+1 种基金The National high technology research and Development program of China(No.2002AA216151)by Ministry of Science and Technology of ChinaKey Project by Chinese Academy of Science(No.KSCX2-2-08).
文摘We have previously shown a critical role of prolactin (PRL) during maturation and anti-tumor effects of murine natural killer (NK) cells in vitro and in vivo. We extended that study by exploring the ability of human NK cell lines (NK-92 and YT cell) to express PRL receptor (PRL-R) and to respond to PRL stimulation in vitro. Both human NK cell lines constitutively expressed PRL-R on membrane and mRNA transcripts,NK-92 cells contained higher level of PRL-R than YT cells,which correlated to the enhanced capacity of the cells to proliferate and to lyse target cells in response to PRL stimulation in the presence of trace amount of IL-2 or IL-15 in vitro. Two differences between IL-2 and IL-15 in functioning on human NK cells were for the first time observed. PRL synergized with IL-15 to improve proliferation of NK cells in a dose-dependent manner without double peak manifesting like IL-2. Although PRL enhanced the cytotoxicity of IL-2 or IL- 15 activated NK cells,it exerted the function through up-regulating gene expression of perforin without influence of FasL in IL-2-stimulated NK cells,while in IL-15-stimulated NK cells,PRL did the function through up-regulating gene expression of both perforin and FasL but not IFNγ. PRL increased expressions of IL-2Rα on membrane and of IL-2 mRNA in cells,indicating that PRL up-regulated NK cell function by improving positive feedback between IL-2 and IL-2R. The similar results were also observed in network between IL-15 and IL-15R. These data indicate a potential role of PRL in human NK cell modulation.
文摘Experimental data shows that the binding of human prolactin(hPRL)to human prolactin receptor(hPRLr-ECD)is strongly pH-dependent,while the binding of the same receptor to human growth hormone(hGH)is pH-independent.Here we carry in silico analysis of the molecular effects causing such a difference and reveal the role of individual amino acids.It is shown that the computational modeling correctly predicts experimentally determined pKa’s of histidine residues in an unbound state in the majority of the cases and the pH-dependence of the binding free energy.Structural analysis carried in conjunction with calculated pH-dependence of the binding revealed that the main reason for pH-dependence of the binding of hPRL-hPRLr-ECD is a number of salt-bridges across the interface of the complex,while no salt-bridges are formed in the hGH-hPRlr-ECD.Specifically,most of the salt-bridges involve histidine residues and this is the reason for the pH-dependence across a physiological range of pH.The analysis not only revealed the molecular mechanism of the pH-dependence of the hPRL-hPRLr-ECD,but also provided critical insight into the underlying physicchemical mechanism.
基金supported by Fundação para a Ciência e Tecnologia(FCT,I.P.,Portugal,http://www.fct.p)project grants UID/Multi/00709/2013 and UID/Multi/00709/2019ARCB is a recipient of a PhD fellowship funded by the FCT(SFRH/BD/121890/2016)+1 种基金supported by the State Budget of the Portuguese Ministry of Science,Technology and Higher Education,by the European Commission and by the European Social Fund through the“Programa Operacional Regional Centro”funded by the grant“Sociedade Portuguesa de Endocrinologia Diabetes e Metabolismovartis Oncology em Patologia Hipofisária 2019”and the European Regional Development Fund through the“Programa Operacional Regional do Centro(Centro 2020)-Sistema de ApoioàInvestigação Científica e Tecnológica-Programas Integrados de IC&DT”(Project Centro-01-0145-FEDER-000019-C4-Centro de Competências em Cloud Computing).
文摘Prolactin is a polypeptide hormone associated with an extensive variety of biological functions.Among the roles of prolactin in vertebrates,some were preserved throughout evolution.This is the case of its function in the brain,where prolactin receptors,are expressed in different structures of the central nervous system.In the brain,prolactin actions are principally associated with reproduction and parental behavior,and involves the modulation of adult neurogenesis,neuroprotection,and neuroplasticity,especially during pregnancy,thereby preparing the brain to parenthood.Prolactin is mainly produced by specialized cells in the anterior pituitary gland.However,during vertebrate evolution many other extrapituitary tissues do also produce prolactin,like the immune system,endothelial cells,reproductive structures and in several regions of the brain.This review summarizes the relevance of prolactin for brain function,the sources of prolactin in the central nervous system,as well as its local production and secretion.A highlight on the impact of prolactin in human neurological diseases is also provided.
文摘This study aimed to investigate the correlations among androgen receptor （AR） CAG repeat polymorphism, sex hormones and penile length in healthy Chinese young adult men. Two hundred and fifty-three healthy men （aged 22.8 ± 3.1years） were enrolled. The individuals were grouped as CAG short （CAGs） if they harbored repeat length of 〈20 or as CAG long （CAGL） if their CAG repeat length was 〉20. Body height/weight, penile length and other parameters were examined and recorded by the specified physicians; CAG repeat polymorphism was determined by the polymerase chain reaction （PCR） method; and the serum levels of the sex hormones were detected by radioimmunoassay. Student＇s t-test or linear regression analysis was used to assess the associations among AR CAG repeat polymorphism, sex hormones and penile length. This investigation showed that the serum total testosterone （T） level was positively associated with the AR CAG repeat length （P = 0.01）; whereas, no significant correlation of T or AR CAG repeat polymorphism with the penile length was found （P = 0.593）. Interestingly, an inverse association was observed between serum prolactin （PRL） levels and penile length by linear regression analyses （β = -0.024, P = 0.039, 95% confidence interval （CI）： -0.047, 0）. Collectively, this study provides the first evidence that serum PRL, but not T or AR CAG repeat polymorphism, is correlated with penile length in the Han adult population from northwestern China.
文摘Today there is significant information indicating an effect of prolactin on the prostate gland. It has been shown to be involved in mechanisms leading to the synthesis of some proteins such as PSA and cathepsin D, synthesis of citrate and accumulation of zinc. Also, at the behavioral level, prolactin is known to control some aspects of reproduction, including documentation on the physiology of the prostate and the possibility to trigger pathologies in this sex gland. Although the later still is not clear, there is a correlation between the level of prolactin and the presence of prostate pathologies. Thus, the aim of this review is to show how prolactin is involved in the progression of some pathologies of this male sexual gland.
文摘目的比较阿立哌唑与利培酮治疗女性首发精神分裂症患者的疗效和血浆催乳素水平变化及其与多巴胺D3受体(DRD3)基因Ser9Gly(rs6280)多态性的关联。方法选择完成8周阿立哌唑或利培酮治疗的女性首发精神分裂症患者各60例,于治疗前和治疗8周后分别评测阳性与阴性症状量表(positive and negativesymptom scale,PANSS)。采用放射免疫法检测血浆催乳素水平,DNA测序技术检测DRD3基因Ser9Gly多态性,分析DRD3基因Ser9Gly多态性与两药疗效及血浆催乳素变化的关联。结果治疗8周后,两组PANSS减分率的差异无统计学意义[(59.79±23.48)vs.(63.30±22.66),P>0.05],但利培酮组血浆催乳素的变化值高于阿立哌唑组[(26.92±9.48)vs.(-25.25±8.07),P<0.05]。利培酮组中C等位基因携带者的血浆催乳素的增加明显高于未携带者[(52.48±27.01)ng/mL vs(36.07±17.46),P<0.05];而阿立哌唑组中未见此差异[(-23.27±8.36)vs.TT(-26.05±8.11),P>0.05]。两组8周后PANSS减分率(%)与DRD3基因Ser9Gly的差异均无统计学意义:阿立哌唑组[CC+CT(57.83±19.94)vs.TT(56.84±18.46),P>0.05];利培酮组[CC+CT(53.94±21.08)vs.TT(60.38±19.37),P>0.05]。结论阿立哌唑治疗女性首发精神分裂症疗效与利培酮相当,但引起血浆催乳素水平变化的幅度较小;利培酮引起血浆催乳素水平增加可能与DRD3基因Ser9Gly多态性有关联。
