Sublethal Hyperthermia Transiently Disrupts Cortisol Steroidogenesis in Adrenocortical Cells.
Sublethal Hyperthermia Transiently Disrupts Cortisol Steroidogenesis in Adrenocortical Cells.
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献血性高温会瞬时破坏肾上腺皮质细胞中的皮质醇类固醇生成。
DOI：
10.1210/endocr/bqad046
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发表时间：
2023-03-13
期刊：
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
原发性醛固酮增多症是继发性高血压最常见的原因。肾上腺切除术的一线治疗是切除肾上腺结节和邻近的正常组织，限制了对单侧疾病患者的适用性。使用热消融代表了一种新兴的方法，作为单侧和双侧疾病的可能微创治疗，靶向和破坏分泌过多的醛固酮腺瘤，同时保留相邻的正常肾上腺皮质。为了确定暴露于高温时对肾上腺细胞的损伤程度，在37 ° C至50°C的温度下用高温处理类固醇生成肾上腺皮质细胞系H295 R和HAC 15，在用毛喉素和ANGII刺激后评价高温对类固醇生成的影响。处理后立即和7天分析细胞死亡、类固醇生成酶和损伤标记物（HSP 70/90）的蛋白/mRNA表达以及类固醇分泌。在高温处理后，42°C和45°C不会诱导细胞死亡，被认为是亚致死剂量，而≥50°C会导致肾上腺细胞过度死亡。亚致死高温（45°C）导致治疗后皮质醇分泌立即显著减少，同时差异性地影响各种类固醇生成酶的表达，尽管类固醇生成在治疗后7天明显恢复。因此，在热消融过程中发生在过渡区的亚致死性高温诱导了体外肾上腺皮质细胞中皮质醇类固醇生成的短暂、不持续的抑制。
Primary aldosteronism is the most common cause of secondary hypertension. The first-line treatment adrenalectomy resects adrenal nodules and adjacent normal tissue, limiting suitability to those who present with unilateral disease. Use of thermal ablation represents an emerging approach as a possible minimally invasive therapy for unilateral and bilateral disease, to target and disrupt hypersecreting aldosterone-producing adenomas, while preserving adjacent normal adrenal cortex. To determine the extent of damage to adrenal cells upon exposure to hyperthermia, the steroidogenic adrenocortical cell lines H295R and HAC15 were treated with hyperthermia at temperatures between 37 and 50°C with the effects of hyperthermia on steroidogenesis evaluated following stimulation with forskolin and ANGII. Cell death, protein/mRNA expression of steroidogenic enzymes and damage markers (HSP70/90), and steroid secretion were analyzed immediately and 7 days after treatment. Following treatment with hyperthermia, 42°C and 45°C did not induce cell death and were deemed sublethal doses while ≥50°C caused excess cell death in adrenal cells. Sublethal hyperthermia (45°C) caused a significant reduction in cortisol secretion immediately following treatment while differentially affecting the expression of various steroidogenic enzymes, although recovery of steroidogenesis was evident 7 days after treatment. As such, sublethal hyperthermia, which occurs in the transitional zone during thermal ablation induces a short-lived, unsustained inhibition of cortisol steroidogenesis in adrenocortical cells in vitro.
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影响因子：
4.1
作者：
Castillo, Ana F.;Orlando, Ulises;Podesta, Ernesto J.
通讯作者：
Podesta, Ernesto J.
DOI：
10.1016/j.coemr.2019.08.009
发表时间：
2019-10-01
影响因子：
--
作者：
Pinto, Emilia Modolo;Kiseljak-Vassiliades, Katja;Hantel, Constanze
通讯作者：
Hantel, Constanze
影响因子：
3.2
作者：
O'Shea, Paula M.;O'Donoghue, Darragh;Dennedy, Michael C.
通讯作者：
Dennedy, Michael C.
影响因子：
8.3
作者：
Heinze, Britta;Fuss, Carmina T.;Hahner, Stefanie
通讯作者：
Hahner, Stefanie
影响因子：
5.8
作者：
Funder, John W.;Carey, Robert M.;Young, William F., Jr.
通讯作者：
Young, William F., Jr.