It is well established that endotoxemia disrupts reproductive capability, and several proinflammatory cytokines, especially IL-1 beta, IL-6, and TNF-alpha in the brain, have been implicated in this endocrine aberration. However, no previous study has directly compared the effects of the three major proinflammatory cytokines (IL-1 beta, IL-6, and TNF-alpha) on the in vivo release of hypothalamic GnRH, a secretagogue of LH from the pituitary. Therefore, in this study, we addressed this issue with two complementary approaches involving push-pull perfusion in freely moving ovariectomized female rats. First, we examined the effects of systemic lipopolysaccharide (LPS) treatment on the release of plasma LH, and of GnRH, IL-1 beta, IL-6, and TNF-alpha in the hypothalamic medial preoptic area (MPOA), where the majority of GnRH neuronal perikarya are located. LPS inhibited the secretion of both LH and GnRH and concomitantly stimulated the release of all three cytokines. We next tested the effects of direct MPOA perfusion with the respective cytokines (at three different concentrations each) on the GnRH and LH secretion. IL-1 beta and TNF-alpha, at the concentrations that were observed in the MPOA after the LPS injection, were equipotent in inhibiting the GnRH-LH system, whereas IL-6 was ineffective (even at a supraphysiological concentration). These results strongly suggest that IL-1 beta and TNF-alpha may represent the major proinflammatory cytokines mediating the LPS-induced suppression of GnRH and LH release, whereas the role of IL-6 seems to be insignificant.
Kisspeptin, encoded by the Kiss1 gene, has attracted attention as a key candidate neuropeptide in controlling puberty and reproduction via regulation of gonadotrophin-releasing hormone (GnRH) secretion in mammals. Pioneer studies with Kiss1 or its cognate receptor Gpr54 knockout (KO) mice showed the indispensable role of kisspeptin-GPR54 signalling in the control of animal reproduction, although detailed analyses of gonadotrophin secretion, especially pulsatile and surge-mode of luteinising hormone (LH) secretion, were limited. Thus, in the present study, we have generated Kiss1 KO rats aiming to evaluate a key role of kisspeptin in governing reproduction via pulse and surge modes of GnRH/LH secretion. Kiss1 KO male and female rats showed a complete suppression of pulsatile LH secretion, which is responsible for folliculogenesis and spermatogenesis, and an absence of puberty and atrophic gonads. Kiss1 KO female rats showed no spontaneous LH/follicle-stimulating hormone surge and an oestrogen-induced LH surge, suggesting that the GnRH surge generation system, which is responsible for ovulation, does not function without kisspeptin. Furthermore, challenge of major stimulatory neurotransmitters, such as monosodium glutamate, NMDA and norepinephrine, failed to stimulate LH secretion in Kiss1 KO rats, albeit they stimulated LH release in wild-type controls. Taken together, the results of the present study confirm that kisspeptin plays an indispensable role in generating two modes (pulse and surge) of GnRH/gonadotrophin secretion to regulate puberty onset and normal reproductive performance. In addition, the present study suggests that kisspeptin neurones play a critical role as a hub integrating major stimulatory neural inputs to GnRH neurones, using newly established Kiss1 KO rats, which serve as a useful model for detailed analysis of hormonal profiles.
Ionic polymer-metal composite (IPMC), which is one of the electro-active polymer actuators, is expected as artificial muscles for robots. An interesting property of IPMC is that it requires water to work, therefore it is suitable for underwater robots. In this paper, we developed an underwater robot which mimics rajiform swimming, that is the swimming form of a ray fish. Fins are designed using sixteen IPMCs. For autonomous operation, miniaturization of the electrical devices such as a micro controllers and small amplifiers are performed. A simple traveling wave control input is employed to generate moment on the fin. In the experiment, propulsion speed is measured under various control parameters. Furthermore, incremental wave of the fin is observed although the amplitude of the control input is spatially uniform. We also discuss this phenomenon from the point of view of interaction between elasticity of the actuator and fluid dynamics.
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