Purpose: For a variety of diseases, gender is a known risk factor. However, mechanisms behind this susceptibility are poorly understood. Interestingly, glucocorticoid signaling can exert sexually dimorphic effects, which is of interest in relation to gender-dependent disease susceptibility. Central serous chorioretinopathy (CSC), a type of macular degeneration characterized by subretinal fluid accumulation, is a disease in which both glucocorticoid use and male gender are important risk factors. CSC is presumed to be the result of leakage from the vasculature of the eye, and therefore endothelial cells are of particular interest. This study describes the effect of cortisol on human primary endothelial cells (ECs) from both males and females, in order to study intrinsic differences of the cortisol response between males and females.

Methods: Human primary ECs from 5 males and 5 females were isolated from cadaveric donor eyes by enzymatic digestion and magnetic-activated cell sorting. The cells were treated in vitro with either cortisol (10^-6 M) or vehicle (0.01% ethanol) medium, after which RNA was isolated and whole transcriptome analysis was performed on a Novaseq Illumina platform.

Results: Bioinformatic analysis showed statistically significant upregulation of 153 genes and downregulation of 169 genes. Genders were identified based on basal expression levels of Y-chromosome genes. However, variance in differential gene expression was largely explained by cortisol treatment, and could not be explained by gender.  

Conclusions: In summary, this study describes 322 genes regulated by cortisol in primary human ECs. Gender-specific gene expression profiles could not be identified based on differentially expressed genes induced by cortisol. A weak interaction was observed between gender and cortisol treatment, suggesting that gender differences are not driven by intrinsic differences on the cellular level, but possibly by hormonal context in vivo.