Abstract. Metastin/kisspeptin, the KiSS-1 gene product, has been identified as an endogenous ligand of GPR54 that reportedly regulates GnRH/LH surges and estrous cyclicity in female rats. The aim of the present study was to determine if metastin/kisspeptin neurons are a target of estrogen positive feedback to induce GnRH/LH surges. We demonstrated that preoptic area (POA) infusion of the antirat metastin/kisspeptin monoclonal antibody blocked the estrogen-induced LH surge, indicating that endogenous metastin/kisspeptin released around the POA mediates the estrogen positive feedback effect on GnRH/LH release. Metastin/kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) may be responsible for mediating the feedback effect because the percentage of c-Fosexpressing KiSS-1 mRNA-positive cells to total KiSS-1 mRNA-positive cells was significantly higher in the afternoon than in the morning in the anteroventral periventricular nucleus (AVPV) of high estradiol (E2)-treated females. The percentage of c-Fos-expressing metastin/kisspeptin neurons was not different between the afternoon and morning in the arcuate nucleus (ARC). Most of the KiSS-1 mRNA expressing cells contain ERα immunoreactivity in the AVPV and ARC. In addition, AVPV KiSS-1 mRNA expressions were highest in the proestrous afternoon and lowest in the diestrus 1 in females and were increased by estrogen treatment in ovariectomized animals. On the other hand, the ARC KiSS-1 mRNA expressions were highest at diestrus 2 and lowest at proestrous afternoon and were increased by ovariectomy and decreased by high estrogen treatment. Males lacking the surge mode of GnRH/LH release showed no obvious cluster of metastin/kisspeptin-immunoreactive neurons in the AVPV when compared with high E2-treated females, which showed a much greater density of these neurons. Taken together, the present study demonstrates that the AVPV metastin/kisspeptin neurons are a target of estrogen positive feedback to induce GnRH/LH surges in female rats.

The proportion of having keitai (Japanese mobile phone) has increased rapidly in young children. To research how junior high school students use their own keitai and to examine the impact of using it on their psychology, especially on their friendship, we recruited 651 students, grade 8, from five public junior high schools in the Tokyo metropolitan area. Each student participant completed a questionnaire that we had created. The response rates were 88.8% (n = 578) for participants. The proportion of having their own keitai was 49.3% (n = 285) and that of not having it was 50.7% (n = 293). We found that they used it much more frequently for e-mail than as a phone. Most of them exchanged e-mails between schoolmates, and more than a half of them exchanged e-mails more than 10 times a day. Sociable students estimated that their own keitai was useful for their friendship. But they experienced some insecurity or started staying up late at night engaged in e-mail exchanges, and they thought that they could not live without their own keitai. Our findings suggest that keitai having an e-mail function play a big part in the junior high-school students' daily life, and its impact on students' friendships, psychology, or health should be discussed among students to prevent keitai addiction.

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