German Cancer Research Center (DKFZ), Heidelberg, Germany.
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Heidelberg, Germany.
Nature. 2020 Aug;584(7821):415-419. doi: 10.1038/s41586-020-2462-y. Epub 2020 Jul 8.
Sexual dimorphism arises from genetic differences between male and female cells, and from systemic hormonal differences. How sex hormones affect non-reproductive organs is poorly understood, yet highly relevant to health given the sex-biased incidence of many diseases. Here we report that steroid signalling in Drosophila from the ovaries to the gut promotes growth of the intestine specifically in mated females, and enhances their reproductive output. The active ovaries of the fly produce the steroid hormone ecdysone, which stimulates the division and expansion of intestinal stem cells in two distinct proliferative phases via the steroid receptors EcR and Usp and their downstream targets Broad, Eip75B and Hr3. Although ecdysone-dependent growth of the female gut augments fecundity, the more active and more numerous intestinal stem cells also increase female susceptibility to age-dependent gut dysplasia and tumorigenesis, thus potentially reducing lifespan. This work highlights the trade-offs in fitness traits that occur when inter-organ signalling alters stem-cell behaviour to optimize organ size.
性二型性是由雌雄细胞的遗传差异以及系统性激素差异引起的。性激素如何影响非生殖器官尚不清楚，但鉴于许多疾病的性别偏向发病率很高，这与健康密切相关。在这里，我们报告称，果蝇从卵巢到肠道的类固醇信号传导促进了交配后雌性特定的肠道生长，并增强了它们的生殖能力。苍蝇的活跃卵巢会产生类固醇激素蜕皮激素，通过类固醇受体 EcR 和 Usp 及其下游靶标 Broad、Eip75B 和 Hr3，蜕皮激素在两个不同的增殖阶段刺激肠道干细胞的分裂和扩张。虽然雌性肠道依赖蜕皮激素的生长增加了繁殖力，但更活跃和更多数量的肠道干细胞也增加了雌性对年龄相关肠道发育不良和肿瘤形成的易感性，从而可能缩短寿命。这项工作强调了当器官间信号改变干细胞行为以优化器官大小时，适应性特征之间会出现权衡。
