性激素对肠道干细胞的关键调控作用
廖联明 编译
在第一个研究性激素对肠道干细胞影响的研究中,科学家们提出了新的见解,表明在结构和功能上与人体类固醇激素相似的类固醇性激素,如何彻底改变肠干细胞的行为方式,最终影响到肠道器官的整体结构和功能。作者发现,蜕皮激素,一种由果蝇产生的类固醇激素,它能刺激肠道干细胞的生长,使雌性果蝇的肠道变大,并诱导其他显著的变化。这项研究还提出了一种解释肠道干细胞在正常肠道功能中的性别差异性作用的机制。此外,这项还研究提出肠道激素可能加速肿瘤恶化的证据。犹他大学亨斯迈癌症研究所(HCI)和德国癌症研究中心(DKFZ)联合报道了这一发现,研究结果发表在《自然》杂志上。
Journal Reference:
Fitness trade-offs incurred by ovary-to-gut steroid signalling in Drosophila. Nature, 2020; DOI: 10.1038/s41586-020-2462-y
New clues about the critical role of sex hormones in stem cell control
In one of the first studies addressing the role of sex hormones' impact on stem cells in the gut, scientists outline new insights showing how a steroidal sex hormone, that is structurally and functionally similar to human steroid hormones, drastically alters the way intestinal stem cells behave, ultimately affecting the overarching structure and function of this critical organ. The authors found that ecdysone, a steroid hormone produced by fruit flies, stimulates intestinal stem cell growth and causes the gut of the female fruit fly to grow in size, and induces other critical changes. The study also provides a mechanism to account for sex-specific roles for intestinal stem cells in normal gut function. Moreover, the research presents evidence that gut hormones may accelerate tumor development. The findings, reported jointly by Huntsman Cancer Institute (HCI) at the University of Utah (U of U) and the German Cancer Research Center (DKFZ), are published in the journal Nature.
Bruce Edgar, PhD, a professor of oncological sciences at the U of U, together with Aurelio Teleman, PhD, professor at Heidelberg University jointly led the work. They asked whether sex hormones affect intestinal stem cells' ability to multiply and contribute to gut growth.
We knew that male and female fruit flies exhibited differences in their intestine -- for example, the female's intestine is larger than the male's, and females develop intestinal tumors much more readily than males -- but we didn't know why.
This study adds significant insights into these differences, and how they arise.
The Edgar and Teleman teams found that ecdysone, a sex-specific hormone, can drastically alter the growth properties of stem cells in an organ that, remarkably, is not directly involved in reproduction. They found that these changes affect the structure and function of the entire organ. They discovered that subjecting male flies to ecdysone caused their otherwise slow dividing stem cells to divide as fast as in females, leading to intestinal growth in males as well. This suggests that the limiting difference between the division of stem cells in male and female flies is the circulating levels of the hormone.
This process confers both advantages and disadvantages to the female fruit fly during the course of its life. Initially, more ecdysone in females helps with the evolutionarily critical processes of reproduction. It promotes gut enlargement, facilitating nutrient absorption, which helps the fly lay more eggs. But later in life, the ecdysone hormone, produced by the ovaries, eventually causes gut disfunction that can shorten the lifespan in female fruit flies by creating an environment that favors tumor growth. While humans don't produce ecdysone, they do have related steroid hormones such as estrogen, progesterone and testosterone, which have similar mechanisms of action.
The study provides conclusive evidence that sex hormones alter the behavior of non-sex organs like the intestine. The long-term implications of this research may include exploration of new paths to treating human cancers.
According to the researchers, understanding whether a similar stem cell-hormone relationship operates in human organs will require further studies. They plan to explore this in the future. In addition to the critical role played by sex hormones in intestinal stem cell behavior, the authors believe this study in Drosophila potentially unveils a new mechanism that may play out in human physiology and pathology. Insights from this study add to a growing body of work showing that the incidence cancers of non-reproductive organs, including colon and gastric cancers, are different in males and females.