Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Medical Science Room 362A, 635 North Barnhill Drive, Indianapolis, IN 46202-5120, USA.
Nat Rev Endocrinol. 2011 Jul 26;7(12):727-37. doi: 10.1038/nrendo.2011.119.
The anterior pituitary gland secretes hormones that regulate developmental and physiological processes, including growth, the stress response, metabolic status, reproduction and lactation. During embryogenesis, cellular determination and differentiation events establish specialized hormone-secreting cell types within the anterior pituitary gland. These developmental decisions are mediated in part by the actions of a cascade of transcription factors, many of which belong to the homeodomain class of DNA-binding proteins. The discovery of some of these regulatory proteins has facilitated genetic analyses of patients with hormone deficiencies. The findings of these studies reveal that congenital defects-ranging from isolated hormone deficiencies to combined pituitary hormone deficiency syndromes-are sometimes associated with mutations in the genes encoding pituitary-acting developmental transcription factors. The phenotypes of affected individuals and animal models have together provided useful insights into the biology of these transcription factors and have suggested new hypotheses for testing in the basic science laboratory. Here, we summarize the gene regulatory pathways that control anterior pituitary development, with emphasis on the role of the homeodomain transcription factors in normal pituitary organogenesis and heritable pituitary disease.
垂体前叶分泌的激素调节发育和生理过程，包括生长、应激反应、代谢状态、生殖和哺乳。在胚胎发生过程中，细胞决定和分化事件在前垂体中建立了专门的激素分泌细胞类型。这些发育决策部分受转录因子级联反应的调节，其中许多转录因子属于 DNA 结合蛋白的同源域类。这些调节蛋白的发现促进了对激素缺乏症患者的遗传分析。这些研究的结果表明，先天性缺陷——从孤立的激素缺乏到联合垂体激素缺乏综合征——有时与编码垂体作用发育转录因子的基因突变有关。受影响个体和动物模型的表型为这些转录因子的生物学提供了有用的见解，并为基础科学实验室的测试提出了新的假设。在这里，我们总结了控制垂体前叶发育的基因调控途径，重点介绍了同源域转录因子在正常垂体发生和遗传性垂体疾病中的作用。
