生殖 Reproduction

P1-1-155 GnRHニューロンでGABAの興奮性入力を抑制性に変化させると生殖機能に異常がみられる Modulation of excitatory action of GABA in GnRH neurons in vivo cause impairment of fertility ○渡部美穂1,2, 鍋倉淳一2, 福田敦夫1 ○Miho Watanabe1,2, Junichi Nabekura2, Atsuo Fukuda1 浜松医大・神経生理1, 生理研・成体恒常機能2 Dept Neurophysiol, Hamamatsu Univ School of Medicine, Shizuoka1, Division of Homeostatic Development, NIPS, Aichi2 Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway for the central regulation of reproduction. GABA has long been implicated as one of the major players in the regulation of GnRH secretions. Previously, we reported that GABA, the main inhibitory neurotransmitter in the adult brain, exerts an excitatory action in adult GnRH neurons. GABA acts excitatory when [Cl-]i is high, due to the high expression of the Na+-K+-2Cl- cotransporter (NKCC1), which mediates inward transport of Cl-, and the low expression of the K+-Cl- cotransporter (KCC2), which excludes Cl- out of the cell. The decreased expression of NKCC1 and increased expression of KCC2 switches the GABA response from excitatory to inhibitory. To examine the functional role of the excitatory action of GABA in neuronal function in vivo, we generated transgenic mice with conditional overexpression of KCC2 or knockout of NKCC1 restricted in specific neuronal populations in a reversible fashion using tetracycline controlled gene expression system. We can control the temporal and regional expression of KCC2 or NKCC1. We investigated the role of excitatory action of GABA in GnRH neurons using the mice that the excitatory action of GABA can be modulated restricted in GnRH neurons. Female mice, which expressed KCC2 in GnRH neurons, showed low rate of pregnancy and abnormal estrous cyclicity. These results suggest that the excitatory action of GABA on GnRH neurons has an important role in the female reproduction.

P1-1-156 SF-1ノックアウトマウスのPOAにおけるプロゲステロン受容体とkisspeptinの発現 Immunoreactivity of progesterone receptor and kisspeptin in the developing preoptic area of SF-1 knockout mice ○池田やよい1, 加藤朋子3, 加藤大貴2, 高橋幸子1, 駒田致和1 ○Yayoi Ikeda1, Tomoko Kato3, Tomoki Kato2, Sachiko Takahashi1, Munekazu Komada1 愛知学院大・歯・解剖1, 愛知学院大・歯・口先天2, 成育セ　システム医学3 Dept Anat, Aichi-Gakuin Univ Sch Dent, Nagoya1, Dev Cong Ano, Aichi-Gakuin Univ Sch Dent, Nagoya2, Dept System BioMed, Natl Cent Child Health Dev, Tokyo3 The preoptic area (POA), which is highly involved in regulating adult reproductive behaviors, is morphologically different between sexes and is affected by neonatal estrogen treatment. We have studied sexual differentiation of this area of a unique agonadal mouse model, SF-1 knockout (KO) mice, which are born without gonads and adrenal glands, and are not exposed to endogenous sex steroids during fetal/neonatal development. Since SF-1 KO mice die shortly after birth due to adrenal insufficiency, we rescued them by replacement of adrenal hormones, and examined expression of progesterone receptor (PR) and kisspeptin during postnatal development, using immunohistochemistry. The number of PR-immunoreactive (-ir) cells in the POA of wild-type (WT) mice was significantly greater in males than in females at postnatal-day (P) 0 and P7. PR-ir in this brain area of SF-1 KO males and females was significantly lower than in WT males, and resembled the values observed in WT females. Kisspeptin, the Kiss1 gene product, has been proposed as an important upstream regulator of the gonadotrophin-releasing hormone system. Kisspeptin expression is sexually dimorphic in rats and mice, with females having greater numbers of kisspeptin-expressing neurons than males in the rostral periventricular area of the third ventricle. We observed kisspeptin-ir in this region as early as P14 in WT females but not WT males, whereas no expression was detected in either sex of SF-1 KO mice at any developmental stage examined. The results indicate that the POA of either male or female SF-1 KO mice did not display sex-specific PR and kisspeptin expression, suggesting a dual role for gonadal hormones for both male- or female-typical brain development.

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