Female sexual receptivity is essential for reproduction of a species. Neuropeptides play the main role in regulating female receptivity. However, whether neuropeptides regulate the establishment of neural circuits for female sexual receptivity is unknown. Here we found the peptide hormone prothoracicotropic hormone (PTTH), which belongs to the insect PG axis, regulated virgin female receptivity through ecdysone during neural maturation in Drosophila melanogaster. We identified PG neurons expressing PTTH as doublesex-positive neurons, they regulated virgin female receptivity before the metamorphosis during the 3rd-instar larval stage. Furthermore, the ecdysone receptor EcR-A in pC1 neurons regulated virgin female receptivity during metamorphosis. The reduced EcR-A in pC1 neurons induced abnormal morphological development of pC1 neurons without changing neural activity. Among all subtypes of pC1 neurons, the function of EcR-A in pC1b neurons was necessary for virgin female copulation rate. These suggested that the changes of synaptic connections between pC1b and other neurons decreased female copulation rate. Moreover, analysis of brain transcriptomes when EcR-A was reduced in pC1 neurons revealed that, additional genes were regulated downstream of EcR-A function in pC1 neurons. The PG axis has similar functional strategy as the HPG axis in mammals to trigger the juvenile–adult transition. Our work suggests a general mechanism underlying which the neurodevelopment during maturation regulates female sexual receptivity.

Prothoracicotropic hormone controls female sexual receptivity through the function of ecdysone in pC1 neurons of Drosophila