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High Colorectal Cancer Rates in Men Linked to Androgen Levels

Colorectal cancer affects the colon area, and it is common among older adults. The incidence of colon cancer in men is more significant than in females. Colorectal cancer begins as polyps (Small, benign clusters of cells) inside the colon. Some polyps develop into cancerous cells, thus causing the disease.

Scientists have persistently sought to understand why colon cancer is more prevalent in men than women. Finally, scientists, through their study, “Androgen Maintains Intestinal Homeostasis by Inhibiting BMP Signaling via Intestinal Stromal Cells,” explain how stem cells and androgens lead to colon cancer.

The researchers said, “We report the roles of androgen in proliferation and differentiation of intestinal stem cells via targeting of the androgen receptor (AR) on intestinal stromal cells by negatively regulating bone morphogenetic proteins (BMPs) signaling.”

According to previous research, the micro-environment and arrangement of stem cells is similar in colonic and intestinal epithelia. By altering the level of androgen in mice, scientists found out that elevated levels of androgen stimulate intestinal stem cells to divide at a faster rate than usual.

The scientists said, “Orchidectomy (ORX), ovariectomy (OVX), and inhibition of AR in male mouse models were done to investigate the effect of androgens on ISC terminal differentiation. The small intestines were isolated for specific staining and quantification of secretory cells and enterocytes.”

Enteroendocrine, Paneth, and goblet cells increased after orchidectomy compared to controls. The researchers added dihydrotestosterone to reverse the phenomenon. They noted that androgens reduce the number of enterocytes and secretory lineages.  Researchers made the BMP pathway selective inhibitor in ORX males. The results were similar to the reverse influence of exogenous androgens. 

The researchers explained, “Conversely, the AR agonist inhibits ISC differentiation but augments proliferation in ovariectomized mice. Mechanistically, activation of the AR increases expression of BMP antagonists but lowers the expression of BMP4 and Wnt antagonists in primary stromal cells, which promotes intestinal organoid growth. Interestingly, the BMP pathway inhibitor LDN-193189 reverses the ORX-induced effect.”

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