Kita Aya, Imayoshi Itaru, Hojo Masato, Kitagawa Masashi, Kokubu Hiroshi, Ohsawa Ryosuke, Ohtsuka Toshiyuki, Kageyama Ryoichiro, Hashimoto Nobuo
Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Mol Endocrinol. 2007 Jun;21(6):1458-66. doi: 10.1210/me.2007-0039. Epub 2007 Apr 10.
The pituitary gland is composed of two distinct entities: the adenohypophysis, including the anterior and intermediate lobes, and the neurohypophysis, known as the posterior lobe. This critical endocrine organ is essential for homeostasis, metabolism, reproduction, and growth. The pituitary development requires the control of proliferation and differentiation of progenitor cells. Although multiple signaling molecules and transcription factors are required for the proper pituitary development, the mechanisms that regulate the fate of progenitor cells remain to be elucidated. Hes genes, known as Notch effectors, play a crucial role in specifying cellular fates during the development of various tissues and organs. Here, we report that mice deficient for Hes1 and Hes5 display severe pituitary hypoplasia caused by accelerated differentiation of progenitor cells. In addition, this hypoplastic pituitary gland (adenohypophysis) lacks the intermediate lobe and exhibits the features of the anterior lobe only. Hes1 and Hes5 double-mutant mice also lack the neurohypophysis (the posterior lobe), probably due to incomplete evagination of the diencephalon. Thus, Hes genes control not only maintenance of progenitor cells but also intermediate vs. anterior lobe specification during the adenohypophysis development. Hes genes are also essential for the formation of the neurohypophysis.
腺垂体，包括前叶和中间叶；神经垂体，即后叶。这个关键的内分泌器官对于体内平衡、新陈代谢、生殖和生长至关重要。垂体的发育需要控制祖细胞的增殖和分化。尽管垂体的正常发育需要多种信号分子和转录因子，但调节祖细胞命运的机制仍有待阐明。Hes基因作为Notch效应器，在各种组织和器官的发育过程中对细胞命运的决定起着关键作用。在此，我们报告Hes1和Hes5基因缺失的小鼠表现出严重的垂体发育不全，这是由祖细胞分化加速所致。此外，这种发育不全的垂体（腺垂体）缺乏中间叶，仅表现出前叶的特征。Hes1和Hes5双突变小鼠也缺乏神经垂体（后叶），这可能是由于间脑不完全外翻所致。因此，Hes基因不仅控制祖细胞的维持，还在腺垂体发育过程中控制中间叶与前叶的分化。Hes基因对于神经垂体的形成也至关重要。
