Nuclear receptors: structure, function and involvement in disease.

Nuclear hormone receptors are acting as transcription factors in the cell nucleus. They regulate gene expression of hormonal regulated target genes. The role of hormone in the transcriptional process is to modulate and change the nuclear receptor functionality. Receptors contain a DNA binding domain that enables them to bind to hormone response elements of target genes. Nuclear hormone receptors bind to lipophilic hormones produced by the organisms' endocrine system, which links the secretion of hormones directly to regulation of gene expression of responsive tissues. In recent years increasing numbers of naturally occurring mutations of a variety of nuclear hormone receptor genes were identified in patients showing abnormalities in hormonal response. Here, we present an overview of nuclear receptors and their mutant forms which cause human syndromes or are associated with cancer progression. The major scope of this article is to give an overview on the structural-functional relationship and based on that, to understand the effects of naturally occurring receptor mutants on the molecular level. Thereby, functional aberrations of naturally occurring receptors for androgen, glucocorticoids, mineralocorticoid, estrogen, vitamin D3, retinoic acid, and thyroid hormone as well as the orphan receptor DAX1 are discussed.