Direct evidence that KNDy neurons maintain gonadotropin pulses and folliculogenesis as the GnRH pulse generator
Mayuko Nagae, Yoshihisa Uenoyama, Saki Okamoto, Hitomi Tsuchida, Kana Ikegami, Teppei Goto, Sutisa Majarune, Sho Nakamura, Makoto Sanbo, Masumi Hirabayashi, Kenta Kobayashi, Naoko Inoue, Hiroko Tsukamura
Abstract
Significance Reports suggest that at least 25% of women suffering from reproductive disorders are due to hypothalamic dysfunction. Pulsatile gonadotropin-releasing hormone (GnRH) regimens are used for infertile women. Thus, elucidation of the GnRH/gonadotropin pulse generator is warranted to improve therapeutic approaches for these disorders. Normal pulsatile gonadotropin release and folliculogenesis were rescued by transfecting the kisspeptin gene ( Kiss1 ) into the hypothalamic neurokinin B (NKB) neurons in global Kiss1 knockout infertile female rats but not by transfecting outside the NKB neurons. Our results demonstrate that kisspeptin/NKB/dynorphin A (KNDy) neurons serve as the GnRH pulse generator, and >20% KNDy neurons are enough to maintain GnRH/gonadotropin pulses and folliculogenesis in female rats. The findings provide a potential therapeutic aspect for hypothalamic reproductive disorders.