University of Michigan Medical School, Ann Arbor, MI 41809-5618, USA.
Mol Cell Endocrinol. 2010 Jul 8;323(1):4-19. doi: 10.1016/j.mce.2009.12.012. Epub 2009 Dec 16.
Defects in pituitary gland organogenesis are sometimes associated with congenital anomalies that affect head development. Lesions in transcription factors and signaling pathways explain some of these developmental syndromes. Basic research studies, including the characterization of genetically engineered mice, provide a mechanistic framework for understanding how mutations create the clinical characteristics observed in patients. Defects in BMP, WNT, Notch, and FGF signaling pathways affect induction and growth of the pituitary primordium and other organ systems partly by altering the balance between signaling pathways. The PITX and LHX transcription factor families influence pituitary and head development and are clinically relevant. A few later-acting transcription factors have pituitary-specific effects, including PROP1, POU1F1 (PIT1), and TPIT (TBX19), while others, such as NeuroD1 and NR5A1 (SF1), are syndromic, influencing development of other endocrine organs. We conducted a survey of genes transcribed in developing mouse pituitary to find candidates for cases of pituitary hormone deficiency of unknown etiology. We identified numerous transcription factors that are members of gene families with roles in syndromic or non-syndromic pituitary hormone deficiency. This collection is a rich source for future basic and clinical studies.
垂体腺发生缺陷有时与影响头部发育的先天性异常有关。转录因子和信号通路的损伤解释了其中一些发育综合征。基础研究，包括对基因工程小鼠的特征描述，为理解突变如何产生患者观察到的临床特征提供了一个机制框架。BMP、WNT、Notch 和 FGF 信号通路的缺陷通过改变信号通路之间的平衡，影响垂体原基和其他器官系统的诱导和生长。PITX 和 LHX 转录因子家族影响垂体和头部发育，与临床相关。少数晚期作用的转录因子对垂体具有特异性作用，包括 PROP1、POU1F1（PIT1）和 TPIT（TBX19），而其他转录因子，如 NeuroD1 和 NR5A1（SF1）则是综合征性的，影响其他内分泌器官的发育。我们对发育中的小鼠垂体转录的基因进行了调查，以寻找病因不明的垂体激素缺乏症病例的候选基因。我们鉴定了许多转录因子，它们是在综合征性或非综合征性垂体激素缺乏症中发挥作用的基因家族的成员。这个集合是未来基础和临床研究的丰富来源。
