Fitness trade-offs incurred by ovary-to-gut steroid signaling in Drosophila

Sexual dimorphism arises from genetic differences between male and female cells, and from systemic hormonal differences(1–3). How sex hormones affect non-reproductive organs is poorly understood, yet highly health-relevant given the sex-biased incidence of most diseases(4). Here we report that steroid signaling from the Drosophila ovaries to the gut promotes growth of the intestine specifically in mated females, enhancing their reproductive output. The fly’s active ovaries produce the steroid hormone ecdysone, which stimulates intestinal stem cell (ISC) division and pool expansion in two distinct proliferative phases via its receptor EcR/Usp and downstream targets Broad, Eip75B and Hr3. Although ecdysone-dependent gut growth augments female fecundity, the more active, more numerous ISCs also increase female susceptibility to age-dependent gut dysplasia and tumorigenesis, potentially reducing lifespan. This work highlights the fitness trait trade-offs that occur when inter-organ signaling alters stem cell behavior to optimize organ size.