PT - JOURNAL ARTICLE AU - Aaron Leiblich AU - Josephine E. E. U. Hellberg AU - Aashika Sekar AU - Carina Gandy AU - Siamak Redhai AU - Mark Wainwright AU - Pauline Marie AU - Deborah C. I. Goberdhan AU - Freddie C. Hamdy AU - Clive Wilson TI - Mating Induces Switch From Hormone-Dependent to – Independent Steroid Receptor-Mediated Growth in <em>Drosophila</em> Prostate-Like Cells AID - 10.1101/533976 DP - 2019 Jan 01 TA - bioRxiv PG - 533976 4099 - http://biorxiv.org/content/early/2019/01/29/533976.short 4100 - http://biorxiv.org/content/early/2019/01/29/533976.full AB - Male reproductive glands like the mammalian prostate and the paired Drosophila melanogaster accessory glands secrete seminal fluid components that enhance fecundity. In humans, the prostate grows throughout adult life, stimulated by environmentally regulated endocrine and local androgens. We previously showed that in each fly accessory gland, secondary cells (SCs) and their nuclei also grow in adults, a process enhanced by mating and controlled by bone morphogenetic protein (BMP) signalling. Here we demonstrate that BMP-mediated SC growth is dependent on the receptor for the developmental steroid, ecdysone, whose concentration reflects socio-sexual experience in adults. BMP signalling regulates ecdysone receptor (EcR) levels post-transcriptionally, partly via EcR’s N-terminus. Nuclear growth in virgin males is ecdysone-dependent. However, mating activates genome endoreplication to drive additional BMP-mediated nuclear growth via a cell type-specific form of hormone-independent EcR signalling. In virgin males with low ecdysone levels, this mechanism ensures resources are conserved. However, by switching to hormone-independence after mating, this control is overridden to hyper-activate growth of secretory secondary cells. Our data suggest parallels between this physiological, behaviour-induced switch and altered pathological signalling associated with prostate cancer progression.