Male hormones regulate stomach inflammation in mice

Male hormones regulate stomach inflammation in mice

Scientists determined that stomach inflammation is regulated differently in male and female mice after finding that androgens, or male sex hormones, play a critical role in preventing inflammation in the stomach. The finding suggests that physicians could consider treating male patients with stomach inflammation differently than female patients with the same condition. The study was published in Gastroenterology.

Researchers made the discovery after removing adrenal glands from mice of both sexes. Adrenal glands produce glucocorticoids, hormones that have several functions, one of them being suppressing inflammation. With no glucocorticoids, the female mice soon developed stomach inflammation. The males did not. However, after removing androgens from the males, they exhibited the same stomach inflammation seen in the females.

"The fact that androgens are regulating inflammation is a novel idea," said co-corresponding author. "Along with glucocorticoids, androgens offer a new way to control immune function in humans."

While this study provides insight into how inflammation is being regulated in males, the author said additional research is underway to understand the process in females.

Whether inflammation is inside the stomach or elsewhere in the body, the author said rates of chronic inflammatory and autoimmune diseases vary depending on sex. Eight out of 10 individuals with autoimmune disease are women.

The current research focused on stomach glands called pits, which are embedded in the lining of the stomach.

The author said the study showed that glucocorticoids and androgens act like brake pedals on the immune system and are essential for regulating stomach inflammation. In this analogy, glucocorticoids are the primary brakes and androgens are the emergency brakes.

"Females only have one layer of protection, so if you remove glucocorticoids, they develop stomach inflammation and a pre-cancerous condition in the stomach called spasmolytic polypeptide-expressing metaplasia (SPEM)," the author said. "Males have redundancy built in, so if something cuts the glucocorticoid brake line, it is okay, because the androgens can pick up the slack."

The research also offered a possible mechanism — or biological process — behind this phenomenon. In healthy stomach glands, the presence of glucocorticoids and androgens inhibit special immune cells called type 2 innate lymphoid cells (ILC2s). But in diseased stomach glands, the hormones are missing. As a result, ILC2s may act like a fire alarm, directing other immune cells called macrophages to promote inflammation and damage gastric glands leading to SPEM and ultimately cancer.

"ILC2s are the only immune cells that contain androgen receptors and could be a potential therapeutic target," the senior author said.