SEX-BASED differences may be contributing to disparities in inflammation and the increased prevalence of autoimmune disease in females. Eight out of 10 individuals affected by autoimmune diseases are females. In a new study, Jonathon Busada, School of Medicine, West Virginia University, USA, investigated how sex hormones affect stomach inflammation in males and females. He discovered that male sex hormones, androgens, help to keep stomach inflammation in check.
Busada’s study focused on testosterone, the primary male sex hormone, but also investigated glucocorticoids, steroid hormones with anti-inflammatory properties whose production does not vary significantly between males and females. Busada described glucocorticoids as “the brake pedal to the immune system.”
In experiments carried out on mice that were deficient in both glucocorticoids and testosterone, Busada noted that stomach inflammation in male mice increased at the same level as the female mice. Furthermore, when female mice were given testosterone, their inflammation disappeared.
“We were able to completely rescue them from their stomach inflammation,” explained Busada. “We proved that androgens were giving the male mice that double layer of protection from inflammation… This study potentially explains why women have much higher incidence of autoimmune and chronic inflammatory diseases.”
The research findings suggest that clinicians should consider whether disruptive glucocorticoid or androgen signalling is contributing to their patients’ stomach-inflammatory diseases.
Stomach cancer is the fifth most common cause of cancer and the third leading cause of cancer deaths worldwide. “Persistent smouldering inflammation over the course of many, many years is the fertile ground for stomach cancer to grow,” Busada explained. “It’s an important and understudied, human health issue.”
He further stated: “The overarching theme of my lab is to understand what’s controlling the balance between a protective immune response, which is just targeting the infection, and a pathogenic immune response, which is like a toddler throwing a temper tantrum and damaging everything. It looks like androgens may be really important in tipping that balance toward a protective response.”