Nature: Reveals the key role of sex hormones in stem cell control and colorectal cancer.

July 17, 2020 --In the first study to discover the effects of sex hormones on intestinal stem cells, scientists have revealed that steroids -- structurally and functionally similar to human steroid hormones -- dramatically alter the behavior of intestinal stem cells, ultimately affecting the overall structure and function of the vital organThe authors found that molting hormone -- a steroid hormone produced by fruit flies -- stimulates the growth of intestinal stem cells, causing the intestinal tract of female fruit flies to grow and triggering other key changesThe study also provides a mechanism to explain the specific role of sex in intestinal stem cells in normal intestinal functionIn addition, the study provides evidence that hormones in the gut may accelerate tumor developmentThe findings were jointly reported by the Huntsman Cancer Institute (HCI) at the University of Utah and the German Cancer Research Center (DKFZ), which was published recently in the journal NaturePhoto: DrBruce Edgar, a stem cell biologist at NatureHCI, a professor of oncology at the University of Utah, and DrAurelio Teleman of DKFZ at the University of HeidelbergHe wanted to know whether sex hormones affectthe ability of intestinal stem cells to reproduce and promote intestinal growth"To better understand how stem cells regulate, my lab and many laboratories around the world have been studying the guts of fruit flies for some time," Edgar saidWe know that male fruit flies and female fruit flies show differences in their guts -- for example, females have larger intestines than males, and females are more likely to develop intestinal tumors than males -- but we don't know why"This study provides important insights into these differences and how they occurEdgar and Teleman's team found that molting hormone is a gender-specific hormone that can dramatically alter the growth characteristics of stem cells in organs, notably that the organ is not directly related to reproductionThey found that these changes affect the structure and function of the entire organThey found that injecting male fruit flies with molting hormones causes their originally slow-splitting stem cell to split faster, leading to the growth of the male fruit fly's intestinesThis suggests that the limiting difference between stem cell division between male and female fruit flies lies in the level of hormone circulationIn the lifetime of a female fruit fly, this process has its advantages and disadvantages Initially, more molting hormones in the female body helped the evolutionary key process of reproduction It promotes intestinal expansion and nutrient absorption, which helps flies lay more eggs But in later life, the molting hormone produced by the ovaries eventually leads to intestinal dysfunction, creating an environment conducive to tumor growth, thereby shortening the lifespan of female fruit flies Although humans do not produce molting hormones, we have associated steroid hormones such as estrogen, progesterone and testosterone, which have similar mechanisms of action The experimental work of the study was mainly done by Sara Ahmed, a co-doctoral student at the Molekulare Biological Research Center (ZMBH) at the University of Heidelberg and Edgar and Teleman Labs at DKFZ Ahmed has devised experiments that use genetic tools to turn on and off genes of different cell types in the gut and ovaries of fruit flies, which produce metamorphosis "Our study provides conclusive evidence that sex hormones alter the behavior of non-sexual organs, such as the intestines, " Ahmed said She further speculated that the long-term effects of the study could include exploring new ways to treat human cancer Further research is needed to understand whether similar stem cell-hormone relationships play a role in human organs, according to the researchers They plan to explore this in the future In addition to the important role sex hormones play in intestinal stem cell behavior, the authors believe the study of fruit flies may reveal a new mechanism that may play a role in human physiology and pathology, as a growing body shows that the incidence of non-reproductive cancers, including colon and stomach cancers, is different in men and women () Source: New clues from the fruit flies of the critical role of sex hormones in stem cell control Sara Mahmoud H Ahmed et al Fitness trade-off gerby ovary-to-gut-steroid sos signaling in Drosophila, Nature (2020) DOI: 10.1038/s41586-020-2462-y.