Brinkmeier Michelle L, Potok Mary Anne, Cha Kelly B, Gridley Thomas, Stifani Stefano, Meeldijk Jan, Clevers Hans, Camper Sally A
Department of Human Genetics, University of Michigan Medical School, 4301 MSRBIII, Ann Arbor, Michigan 48109-0638, USA.
Mol Endocrinol. 2003 Nov;17(11):2152-61. doi: 10.1210/me.2003-0225. Epub 2003 Aug 7.
Mutations in the prophet of PIT1 gene (PROP1) are the most common cause of multiple pituitary hormone deficiency in humans; however, the mechanism of PROP1 action is not well understood. We report that Prop1 is essential for dorsally restricted expression of a Groucho-related gene, transducin-like enhancer of split 3 (Tle3), which encodes a transcriptional corepressor. Deficiency of a related gene, amino terminal enhancer of split (Aes), causes pituitary anomalies and growth insufficiency. TLE3 and AES have been shown to interact with TCF/LEF (transcripiton factors of the T cell-specific and lymphoid enhancer specific group) family members in cell culture systems. In the absence of TCF4 (Tcf7L2), Prop1 levels are elevated, pituitary hyperplasia ensues and palate closure is abnormal. Thus, we demonstrate that Tcf4 and Aes influence pituitary growth and development, and place Tcf4 and Tle3 in the genetic hierarchy with Prop1.
先知PIT1基因（PROP1）的突变是人类多种垂体激素缺乏症的最常见原因；然而，PROP1的作用机制尚未完全明确。我们报告称，Prop1对于一种与Groucho相关基因——转导素样分裂增强子3（Tle3，编码一种转录共抑制因子）——的背侧受限表达至关重要。相关基因氨基末端分裂增强子（Aes）的缺乏会导致垂体异常和生长不足。在细胞培养系统中，TLE3和AES已被证明可与TCF/LEF（T细胞特异性和淋巴增强子特异性组的转录因子）家族成员相互作用。在缺乏TCF4（Tcf7L2）的情况下，Prop1水平升高，继而出现垂体增生，并且腭闭合异常。因此，我们证明Tcf4和Aes影响垂体的生长和发育，并将Tcf4和Tle3置于与Prop1相关的遗传层级中。
