RESUMO
Kisspeptin plays a pivotal role in pubertal onset and reproductive function. In rodents, kisspeptin perikarya are located in 2 major populations: the anteroventral periventricular nucleus and the hypothalamic arcuate nucleus (ARC). These nuclei are believed to play functionally distinct roles in the control of reproduction. The anteroventral periventricular nucleus population is thought to be critical in the generation of the LH surge. However, the physiological role played by the ARC kisspeptin neurons remains to be fully elucidated. We used bilateral stereotactic injection of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC of adult female rats to investigate the physiological role of kisspeptin neurons in this nucleus. Female rats with kisspeptin knockdown in the ARC displayed a significantly reduced number of both regular and complete oestrous cycles and significantly longer cycles over the 100-day period of the study. Further, kisspeptin knockdown in the ARC resulted in a decrease in LH pulse frequency. These data suggest that maintenance of ARC-kisspeptin levels is essential for normal pulsatile LH release and oestrous cyclicity.
Assuntos
Núcleo Arqueado do Hipotálamo/citologia , Regulação da Expressão Gênica , Kisspeptinas/fisiologia , Neurônios/metabolismo , Reprodução/fisiologia , Animais , Estradiol/metabolismo , Ciclo Estral , Retroalimentação Fisiológica , Feminino , Proteínas de Fluorescência Verde/metabolismo , Imunoensaio , Kisspeptinas/genética , Hormônio Luteinizante/metabolismo , Oligonucleotídeos Antissenso/genética , Ratos , Ratos Wistar , Proteínas Recombinantes/genética , Fatores de TempoAssuntos
Fibrinólise/efeitos dos fármacos , Heparina/farmacologia , Ativadores de Plasminogênio/efeitos dos fármacos , Animais , Heparina/metabolismo , Infarto do Miocárdio/sangue , Infarto do Miocárdio/tratamento farmacológico , Ativadores de Plasminogênio/metabolismo , Trombose/sangue , Trombose/tratamento farmacológicoRESUMO
SK, t-PA or APSAC were incubated in human plasma (adjusted to 300,000 platelets/mm3), in vitro, for up to 90 minutes using concentrations which were equivalent to those achieved in the treatment of AMI patients. Aggregation was measured in response to ADP and collagen. SK inhibited platelet aggregation after a 60 minute incubation. t-PA was less inhibitory and significant effects were only achieved on extended incubation with a higher concentration of activator. APSAC markedly inhibited platelet aggregation in response to both ADP and collagen and the inhibition was achieved earlier than with SK. The difference in temporal response between APSAC and SK was not attributed to differences in systemic plasminogen activation. There was no influence of anti-SK antibody (IgG) on the platelet function response to APSAC or SK. Aspirin inhibited second phase aggregation induced by ADP but even in the presence of aspirin, the net inhibition of platelet aggregation was greater for APSAC than for SK. This marked effect of APSAC on platelet aggregation helps to explain the high initial patency and low re-occlusion rates seen when APSAC is administered to AMI patients.