Pecori Giraldi Francesca, Cassarino Maria Francesca, Sesta Antonella, Terreni Mariarosa, Lasio Giovanni, Losa Marco
Department of Clinical Sciences & Community Health, University of Milan; 20122 Milan, Italy.
Neuroendocrinology Research Laboratory, Istituto Auxologico Italiano, Istituto di Ricerca e Cura a Carattere Scientifico, 20095 Milan, Italy.
Cancers (Basel). 2020 Mar 13;12(3):669. doi: 10.3390/cancers12030669.
(1) Background. Cushing's disease presents gender disparities in prevalence and clinical course. Little is known, however, about sexual dimorphism at the level of the corticotrope adenoma itself. The aim of the present study was to evaluate molecular features of ACTH-secreting pituitary adenomas collected from female and male patients with Cushing's disease. (2) Methods. We analyzed 153 ACTH-secreting adenomas collected from 31 men and 122 women. Adenomas were established in culture and ACTH synthesis and secretion assessed in basal conditions as well as during incubation with CRH or dexamethasone. Concurrently, microarray analysis was performed on formalin-fixed specimens and differences in the expression profiles between specimens from male and female patients identified. (3) Results. ACTH medium concentrations in adenomas obtained from male patients were significantly lower than those observed in adenomas from female patients. This could be observed for baseline as well as modulated secretion. Analysis of corticotrope transcriptomes revealed considerable similarities with few, selected differences in functional annotations. Differentially expressed genes comprised genes with known sexual dimorphism, genes involved in tumour development and genes relevant to pituitary pathophysiology. (4) Conclusions. Our study shows for the first time that human corticotrope adenomas present sexual dimorphism and underlines the need for a gender-dependent analysis of these tumours. Differentially expressed genes may represent the basis for gender-tailored target therapy.
(1) 背景。库欣病在患病率和临床病程方面存在性别差异。然而，关于促肾上腺皮质激素细胞腺瘤本身水平的性别二态性知之甚少。本研究的目的是评估从患有库欣病的女性和男性患者中收集的促肾上腺皮质激素分泌型垂体腺瘤的分子特征。(2) 方法。我们分析了从31名男性和122名女性中收集的153个促肾上腺皮质激素分泌型腺瘤。将腺瘤进行培养，并在基础条件下以及与促肾上腺皮质激素释放激素（CRH）或地塞米松孵育期间评估促肾上腺皮质激素的合成和分泌。同时，对福尔马林固定的标本进行微阵列分析，并确定男性和女性患者标本之间表达谱的差异。(3) 结果。从男性患者获得的腺瘤中促肾上腺皮质激素的培养基浓度显著低于从女性患者腺瘤中观察到的浓度。这在基线以及调节分泌时均可观察到。对促肾上腺皮质激素细胞转录组的分析揭示了相当多的相似性，在功能注释方面只有少数选定的差异。差异表达基因包括具有已知性别二态性的基因、参与肿瘤发生的基因以及与垂体病理生理学相关的基因。(4) 结论。我们的研究首次表明人类促肾上腺皮质激素细胞腺瘤存在性别二态性，并强调了对这些肿瘤进行性别依赖性分析的必要性。差异表达基因可能代表了性别定制靶向治疗的基础。
