Instituto de Tecnologías Biomédicas and Departamento de Ciencias Médicas Básicas, Universidad de La Laguna, La Laguna, Tenerife, Spain.
Instituto de Tecnologías Biomédicas and Departamento de Ciencias Médicas Básicas, Universidad de La Laguna, La Laguna, Tenerife, Spain.
Mol Cell Endocrinol. 2024 Dec 1;594:112389. doi: 10.1016/j.mce.2024.112389. Epub 2024 Oct 17.
The mineralocorticoid and glucocorticoid receptors (MR and GR, respectively) are members of the steroid receptor subfamily of nuclear receptors. Their main function is to act as ligand-activated transcription factors, transducing the effects of corticosteroid hormones (aldosterone and glucocorticoids) by modulating gene expression. Corticosteroid signaling is essential for homeostasis and adaptation to different forms of stress. GR responds to glucocorticoids by regulating genes involved in development, metabolism, immunomodulation and brain function. MR is best known for mediating the effects of aldosterone, a key hormone controlling electrolyte and water homeostasis. In addition to aldosterone, MR binds glucocorticoids (cortisol and corticosterone) with equally high affinity. This ligand promiscuity has important repercussions to understand MR function, as well as glucocorticoid signaling. MR and GR share significant sequence and structural similarities, regulate overlapping sets of genes and are able to interact forming heteromeric complexes. However, the precise role of these heteromers in regulating corticosteroid-regulated transcriptional outcomes remains an open question. In this review, we examine the evidence supporting MR-GR heteromerization, the molecular determinants of complex formation and their possible role in differential regulation of transcription in different cellular contexts and ligand availability.
盐皮质激素受体和糖皮质激素受体（分别为 MR 和 GR）是核受体甾体受体亚家族的成员。它们的主要功能是作为配体激活的转录因子，通过调节基因表达来传递糖皮质激素（醛固酮和糖皮质激素）的作用。皮质类固醇信号对于体内平衡和适应不同形式的应激至关重要。GR 通过调节涉及发育、代谢、免疫调节和大脑功能的基因对糖皮质激素做出反应。MR 最著名的作用是介导醛固酮的作用，醛固酮是一种控制电解质和水体内平衡的关键激素。除了醛固酮外，MR 与糖皮质激素（皮质醇和皮质酮）具有同样高的亲和力。这种配体混杂性对于理解 MR 功能以及糖皮质激素信号具有重要影响。MR 和 GR 具有显著的序列和结构相似性，调节重叠的基因集，并能够形成异源二聚体复合物。然而，这些异源二聚体在调节糖皮质激素调节的转录结果方面的确切作用仍然是一个悬而未决的问题。在这篇综述中，我们考察了支持 MR-GR 异源二聚化的证据、复合物形成的分子决定因素及其在不同细胞环境和配体可用性下对转录的差异调节中的可能作用。
