Cheung Leonard Y M, Okano Hideyuki, Camper Sally A
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Mol Cell Endocrinol. 2017 Jan 5;439:213-223. doi: 10.1016/j.mce.2016.09.005. Epub 2016 Sep 8.
The hypothalamic-pituitary axes are the coordinating centers for multiple endocrine gland functions and physiological processes. Defects in the hypothalamus or pituitary gland can cause reduced growth and severe short stature, affecting approximately 1 in 4000 children, and a large percentage of cases of pituitary hormone deficiencies do not have an identified genetic cause. SOX21 is a protein that regulates hair, neural, and trophoblast stem cell differentiation. Mice lacking Sox21 have reduced growth, but the etiology of this growth defect has not been described. We studied the expression of Sox21 in hypothalamic-pituitary development and examined multiple endocrine axes in these mice. We find no evidence of reduced intrauterine growth, food intake, or physical activity, but there is evidence for increased energy expenditure in mutants. In addition, despite changes in pituitary hormone expression, hypothalamic-pituitary axes appear to be functional. Therefore, SOX21 variants may be a cause of non-endocrine short stature in humans.
下丘脑 - 垂体轴是多种内分泌腺功能和生理过程的协调中心。下丘脑或垂体的缺陷可导致生长发育迟缓及严重身材矮小，约每4000名儿童中就有1人受影响，且很大比例的垂体激素缺乏病例没有明确的遗传病因。SOX21是一种调节毛发、神经和滋养层干细胞分化的蛋白质。缺乏Sox21的小鼠生长减缓，但其生长缺陷的病因尚未明确。我们研究了Sox21在下丘脑 - 垂体发育中的表达，并检测了这些小鼠的多个内分泌轴。我们没有发现宫内生长减缓、食物摄入量或身体活动减少的证据，但有证据表明突变体的能量消耗增加。此外，尽管垂体激素表达发生了变化，但下丘脑 - 垂体轴似乎仍有功能。因此，SOX21变异可能是人类非内分泌性身材矮小的一个原因。
