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The present study used <jats:italic>Kiss1<\/jats:italic> knockout (<jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>) rats to evaluate the role of kisspeptin in the defeminisation\/masculinisation of the brain mechanism that controls sexual behaviours. Castrated adult <jats:italic>Kiss1 <\/jats:italic><jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> males treated with testosterone showed no male sexual behaviours but demonstrated the oestrogen\u2010induced lordosis behaviours found in wild\u2010type females. The sizes of some of the sexual dimorphic nuclei of <jats:italic>Kiss1 <\/jats:italic><jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> male rats are similar to those of females. Plasma testosterone levels at embryonic day 18 and postnatal day 0 (PND0) in <jats:italic>Kiss1 <\/jats:italic><jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> males were high, similar to wild\u2010type males, indicating that perinatal testosterone is secreted in a kisspeptin\u2010independent manner. Long\u2010term exposure to testosterone from peripubertal to adult periods restored mounts and intromissions in <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> males, suggesting that kisspeptin\u2010dependent peripubertal testosterone secretion is required to masculinise the brain mechanism. This long\u2010term testosterone treatment failed to abolish lordosis behaviours in <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> males, whereas kisspeptin replacement at <jats:styled-content style=\"fixed-case\">PND<\/jats:styled-content>0 reduced lordosis quotients in <jats:italic>Kiss1 <\/jats:italic><jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> males but not in <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> females. These results suggest that kisspeptin itself is required to defeminise behaviour in the perinatal period, in cooperation with testosterone. Oestradiol benzoate treatment at <jats:styled-content style=\"fixed-case\">PND<\/jats:styled-content>0 suppressed lordosis quotients in <jats:italic>Kiss1 <\/jats:italic><jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> rats, indicating that the mechanisms downstream of oestradiol work properly in the absence of kisspeptin. There was no significant difference in aromatase gene expression in the whole hypothalamus between <jats:italic>Kiss1 <\/jats:italic><jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content> and wild\u2010type male rats at <jats:styled-content style=\"fixed-case\">PND<\/jats:styled-content>0. Taken together, the present study demonstrates that both perinatal kisspeptin and kisspeptin\u2010independent testosterone are required for defeminisation of the brain, whereas kisspeptin\u2010dependent testosterone during peripuberty to adulthood is needed for masculinisation of the brain in male rats.<\/jats:p>","DOI":"10.1111\/jne.12409","type":"journal-article","created":{"date-parts":[[2016,6,25]],"date-time":"2016-06-25T14:42:45Z","timestamp":1466865765000},"source":"Crossref","is-referenced-by-count":26,"title":["Neonatal Kisspeptin is Steroid\u2010Independently Required for Defeminisation and Peripubertal Kisspeptin\u2010Induced Testosterone is Required for Masculinisation of the Brain: A Behavioural Study Using Kiss1 Knockout Rats"],"prefix":"10.1111","volume":"28","author":[{"given":"S.","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Veterinary Medical Sciences The University of Tokyo Tokyo 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