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

Nature. 2020 Aug;584(7821):415-419. doi: 10.1038/s41586-020-2462-y. Epub 2020 Jul 8.

Abstract

Sexual dimorphism arises from genetic differences between male and female cells, and from systemic hormonal differences1-3. How sex hormones affect non-reproductive organs is poorly understood, yet highly relevant to health given the sex-biased incidence of many diseases4. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Carcinogenesis
  • Cell Proliferation
  • Copulation / physiology
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / anatomy & histology
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / metabolism*
  • Drosophila melanogaster / physiology
  • Ecdysone / metabolism
  • Female
  • Fertility / physiology*
  • Intestinal Mucosa / anatomy & histology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestines / anatomy & histology
  • Intestines / cytology
  • Intestines / growth & development*
  • Intestines / pathology
  • Longevity / physiology*
  • Male
  • Organ Size / physiology*
  • Ovary / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Steroid / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Steroids / metabolism*
  • Transcription Factors / metabolism

Substances

  • Br protein, Drosophila
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Hr3 protein, Drosophila
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Steroids
  • Transcription Factors
  • USP protein, Drosophila
  • ecdysone receptor
  • Eip75B protein, Drosophila
  • Ecdysone