Brain-gonad axes harmonize male mating drive and reproductive strategy via steroid hormones

The interplay between the nervous and reproductive systems, encapsulated by the brain-gonad axis, is pivotal for reproduction. However, it remains largely unclear how hormones released from reproductive system actively regulate male sexual behaviors and mating strategies. Here we find that sexual priming induces an elevated sexual drive in both male mice and Drosophila, triggered by the surge of circulating steroid hormones 20-hydroxyecdysone (20E) in flies and testosterone in mice, respectively. In Drosophila, 20E is released from the male reproductive system upon sexual priming, which is controlled by a descending brain-gonad pathway composed of P1 neurons, Dsk neurons, and Crz/CrzR neurons. In return, 20E activates P1 neurons to elevate and sustain male flies' mating drive. The enhanced mating drive not only fosters consequent mating success but also makes full use of the reproductive materials prepared during the pre-ejaculatory emission stage, e.g., seminal proteins which would otherwise be potentially harmful to males' gonads. Collectively, our study offers insights into how hormones regulate males' reproductive strategies.