title: Neonatal Kisspeptin is Steroid-Independently Required for Defeminisation and Peripubertal Kisspeptin-Induced Testosterone is Required for Masculinisation of the Brain: A Behavioural Study Using Kiss1 Knockout Rats.
abstract: Rodents show apparent sex differences in their sexual behaviours. The present study used Kiss1 knockout (KO) rats to evaluate the role of kisspeptin in the defeminisation/masculinisation of the brain mechanism that controls sexual behaviours. Castrated adult Kiss1 KO males treated with testosterone showed no male sexual behaviours but demonstrated the oestrogen-induced lordosis behaviours found in wild-type females. The sizes of some of the sexual dimorphic nuclei of Kiss1 KO male rats are similar to those of females. Plasma testosterone levels at embryonic day 18 and postnatal day 0 (PND0) in Kiss1 KO males were high, similar to wild-type males, indicating that perinatal testosterone is secreted in a kisspeptin-independent manner. Long-term exposure to testosterone from peripubertal to adult periods restored mounts and intromissions in KO males, suggesting that kisspeptin-dependent peripubertal testosterone secretion is required to masculinise the brain mechanism. This long-term testosterone treatment failed to abolish lordosis behaviours in KO males, whereas kisspeptin replacement at PND0 reduced lordosis quotients in Kiss1 KO males but not in KO females. These results suggest that kisspeptin itself is required to defeminise behaviour in the perinatal period, in cooperation with testosterone. Oestradiol benzoate treatment at PND0 suppressed lordosis quotients in Kiss1 KO 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 Kiss1 KO and wild-type male rats at PND0. Taken together, the present study demonstrates that both perinatal kisspeptin and kisspeptin-independent testosterone are required for defeminisation of the brain, whereas kisspeptin-dependent testosterone during peripuberty to adulthood is needed for masculinisation of the brain in male rats.
authors.affiliation: Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Uenoyama
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ikegami
authors.affiliation: Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Dai
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Takahashi
authors.affiliation: Center for Genetic Analysis of Behaviour, National Institute for Physiological Sciences, Okazaki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirabayashi
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tsukamura
authors.affiliation: Department of Veterinary Medical Sciences, The University of Tokyo, Tokyo, Japan. akeimaed@mail.ecc.u-tokyo.ac.jp.
authors.forename: K-I
authors.initials: KI
authors.lastname: Maeda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002369:Castration; D005260:Female; D055786:Gene Knockout Techniques; D059648:Kisspeptins / Q000235:genetics / Q000502:physiology*; D008297:Male; D012727:Sex Characteristics; D012733:Sex Differentiation / Q000187:drug effects; D012726:Sexual Behavior, Animal; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*
chemical_list: C491406:Kiss1 protein, rat; D059648:Kisspeptins; D013739:Testosterone
keywords: androgen surge; organisational effect; perinatal period; sexual behaviour; sexual differentiation