Regulation of insect steroid hormone biosynthesis by innervating peptidergic neurons

In insects, steroid hormones named ecdysteroids elicit molting and metamorphosis. The prothoracic gland (PG) is a predominant source of ecdysteroids, where their biosynthesis (ecdysteroidogenesis) is regulated by several neuropeptides. Here, we report that FMRFamide-related peptides (FaRPs) regulate ecdysteroidogenesis through direct innervation of the PG in the silkworm Bombyx mori. We purified a previously uncharacterized Bombyx FaRP, DPSFIRFamide, and identified the corresponding Bombyx FMRFamide gene (Bommo-FMRFamide, BRFa), which encodes three additional FaRPs. All BRFa peptides suppressed ecdysteroidogenesis in the PG by reducing cAMP production by means of the receptor for Bommo-myosuppressin, another FaRP we have previously shown to act as a prothoracicostatic factor. BRFa is predominantly expressed in neurosecretory cells of thoracic ganglia, and the neurons in the prothoracic ganglion innervate the PG to supply all four peptides to the gland surface. Electrophysiological recordings during development confirmed the increased firing activity of BRFa neurons in stages with low PG activity and decreased ecdysteroid levels in the hemolymph. To our knowledge, this study provides the first report of peptides controlling ecdysteroidogenesis by direct innervation.