Abstract
(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.
Highlights
ACTH-secreting pituitary adenomas, i.e., Cushing’s disease, are known to occur far more frequently in women than in men [1,2] and, as we first showed some years ago [3], give rise to a somewhat different clinical course in the two sexes
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
Our approach to gender differences was two-fold, on the one side we assessed the secretory status of corticotrope adenomas in culture, on the other we compared the gene expression profile in archival adenomatous specimens
Summary
ACTH-secreting pituitary adenomas, i.e., Cushing’s disease, are known to occur far more frequently in women than in men [1,2] and, as we first showed some years ago [3], give rise to a somewhat different clinical course in the two sexes. Cancers 2020, 12, 669 disease [10,11], suggesting that the corticotrope adenoma itself may harbour features which contribute to gender-dependent differences in Cushing’s disease. On molecular features of ACTH-secreting adenomas from female and male patients, an avenue of research which may yield novel insights into Cushing’s disease pathophysiology and, possibly, provide the basis for tailored diagnostic and therapeutic approaches. The aim of the present study was to evaluate differences in ACTH-secreting adenomas collected from female and male patients. Our approach to gender differences was two-fold, on the one side we assessed the secretory status of corticotrope adenomas in culture, on the other we compared the gene expression profile in archival adenomatous specimens
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