Kisspeptin neurons are essential for the coordinated regulation of reproduction and sexual behaviors
Figure: Three functionally as well as morphologically different types of GnRH neurons (GnRH1~3) exist in the vertebrate brains; (1) the GnRH1 neurons function to stimulate the release of gonadotropic hormones from the pituitary, (2) the GnRH2 neurons and (3) the GnRH3 neurons are suggested to function as neuromodulators that facilitate the motivational state for sexual behaviors. All of these GnRH neurons are suggested to express kisspeptin receptors (GPR54) and are thus the target neurons of kisspeptin, which implies that the kisspeptin neurons are essential for the coordinated regulation of reproduction and sexual behaviors. We plan to verify this working hypothesis by using the transgenic Medaka brain in which GnRH and/or kisspeptin neurons express fluorescent proteins or other functional proteins.
We identified a novel physiologically active peptide, kisspeptin, for the first time in the brain of nonmammalian species. Kisspeptin has been reported to facilitate sexual maturation and ovulation by directly stimulating gonadotropin-releasing hormone (GnRH) neurons in several mammalian species. Here, we used Medaka for the identification of the gene that encodes kisspeptin (KiSS-1 gene) and the anatomical distribution of KiSS-1 mRNA expressing neurons (KiSS-1 neurons). We found two kisspeptin neuronal populations in the hypothalamic brain regions, called NPPv and NVT. The NVT KiSS-1 neurons were sexually dimorphic in number (male neurons >> female neurons) under the breeding conditions. We also found that the number of KiSS-1 neurons in the NVT but not that in the NPPv was positively regulated by ovarian estrogens. The fact that there were clear differences in the number of NVT KiSS-1 neurons between the fish under the breeding and non-breeding conditions strongly suggests that the steroid-sensitive changes in the KiSS-1 mRNA expression in the NVT occur physiologically, according to the changes in the reproductive state. From the present results, we conclude that the Medaka KiSS-1 neuronal system is involved in the central regulation of reproductive functions, and, given many experimental advantages, the Medaka brain may serve as a good model system to study its physiology.
Published in Endocrinology 149: 2467-2476 (2008 May). Identification of KiSS-1 Product Kisspeptin and Steroid-Sensitive Sexually-Dimorphic Kisspeptin neurons in Medaka (Oryzias latipes)
Shinji Kanda1, Yasuhisa Akazome1, Takuya Matsunaga1, Naoyuki Yamamoto2, Shunji Yamada3, Hiroko Tsukamura3, Kei-ichiro Maeda3, and Yoshitaka Oka1
- Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033 (Japan)
- Laboratory of Fish Biology, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
- Laboratory of Reproductive Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan