Colvin Stephanie C, Mullen Rachel D, Pfaeffle Roland W, Rhodes Simon J
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202-5120, USA.
Pediatr Endocrinol Rev. 2009 Jan;6 Suppl 2:283-90.
The LHX3 and LHX4 LIM-homeodomain proteins are regulatory transcription factors that play overlapping but distinct functions during the establishment of the specialized cells of the mammalian pituitary gland and the nervous system. Recent studies have identified a variety of mutations in the LHX3 and LHX4 genes in patients with combined pituitary hormone deficiency diseases. These patients have complex and variable syndromes involving short stature, metabolic disorders, reproductive system deficits, and nervous system developmental abnormalities. The short stature secondary to growth hormone deficiency is a key feature of the disorders associated with these gene mutations and responds well to supplementation with recombinant growth hormone. Overall, the frequency of mutations in the LHX3 and LHX4 genes in patients with combined pituitary hormone deficiency is low. Mutations in other regulatory genes such as HESX1, PROP1, PIT1 / POU1F1, and GLI2 have been shown to be additional causes of pituitary hormone deficiency, but overall, the etiology of many cases of hypopituitarism is not understood. Further investigation is therefore required to identify other genes, both primary regulatory genes and those with modifier functions, which contribute to pituitary development and function.
LHX3和LHX4 LIM同源域蛋白是调节转录因子，在哺乳动物垂体和神经系统的特化细胞形成过程中发挥重叠但不同的功能。最近的研究在患有联合垂体激素缺乏症的患者中发现了LHX3和LHX4基因的多种突变。这些患者具有复杂多变的综合征，包括身材矮小、代谢紊乱、生殖系统缺陷和神经系统发育异常。生长激素缺乏继发的身材矮小是与这些基因突变相关疾病的关键特征，补充重组生长激素后反应良好。总体而言，联合垂体激素缺乏症患者中LHX3和LHX4基因突变的频率较低。其他调节基因如HESX1、PROP1、PIT1 / POU1F1和GLI2的突变已被证明是垂体激素缺乏的其他原因，但总体而言，许多垂体功能减退病例的病因尚不清楚。因此，需要进一步研究以确定其他基因，包括主要调节基因和具有修饰功能的基因，这些基因有助于垂体的发育和功能。
