(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.