Regional Specialist Hospital in Wroclaw - Research and Development Centre, Wroclaw, Poland; Department of Biochemistry and Molecular Biology, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
Regional Specialist Hospital in Wroclaw - Research and Development Centre, Wroclaw, Poland; Department of Pathology, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
J Card Fail. 2021 Jun;27(6):682-692. doi: 10.1016/j.cardfail.2020.12.024. Epub 2021 Jan 12.
Steroid hormones play an important role in heart failure (HF) pathogenesis, and clinical data have revealed disordered steroidogenesis in male patients with HF. However, there is still a lack of studies on steroid hormones and their receptors during HF progression. Therefore, a porcine model of tachycardia-induced cardiomyopathy corresponding to HF was used to assess steroid hormone concentrations in serum and their nuclear receptor levels in heart tissue during the consecutive stages of HF.
Male pigs underwent right ventricular pacing and developed a clinical picture of mild, moderate, or severe HF. Serum concentrations of dehydroepiandrosterone, testosterone, dihydrotestosterone, estradiol, aldosterone, and cortisol were assessed by enzyme-linked immunosorbent assay. Androgen receptor, estrogen receptor alpha, mineralocorticoid receptor, and glucocorticoid receptor messenger RNA levels in the left ventricle were determined by qPCR.The androgen level decreased in moderate and severe HF animals, while the corticosteroid level increased. The estradiol concentration remained stable. The quantitative real-time polymerase chain reaction revealed the downregulation of androgen receptor in consecutive stages of HF and increased expression of mineralocorticoid receptor messenger RNA under these conditions.
In the HF pig model, deteriorated catabolic/anabolic balance, manifested by upregulation of aldosterone and cortisol and downregulation of androgen signaling on the ligand level, was augmented by changes in steroid hormone receptor expression in the heart tissue.
甾体激素在心力衰竭（HF）发病机制中起着重要作用，临床数据显示男性 HF 患者存在类固醇生成紊乱。然而，关于 HF 进展过程中甾体激素及其受体的研究仍然较少。因此，本研究采用心动过速诱导的心肌病猪模型来评估 HF 连续阶段血清中甾体激素浓度及其心脏组织中核受体水平。
雄性猪接受右心室起搏，并出现轻度、中度或重度 HF 的临床表现。采用酶联免疫吸附试验测定去氢表雄酮、睾酮、二氢睾酮、雌二醇、醛固酮和皮质醇的血清浓度。通过 qPCR 测定左心室雄激素受体、雌激素受体 α、盐皮质激素受体和糖皮质激素受体信使 RNA 水平。在中度和重度 HF 动物中，雄激素水平降低，而皮质类固醇水平升高。雌二醇浓度保持稳定。实时定量聚合酶链反应显示，在 HF 的连续阶段，雄激素受体下调，在这些条件下，矿物质皮质激素受体信使 RNA 的表达增加。
在 HF 猪模型中，心脏组织中甾体激素受体表达的变化加剧了醛固酮和皮质醇的上调以及雄激素信号转导的下调，导致分解代谢/合成代谢平衡恶化。
