A Glycoprotein Hormone Orchestrates Ovarian Development in the Fall Armyworm Spodoptera Frugiperda

Glycoprotein hormones serve as critical regulators of diverse physiological processes in both vertebrates and invertebrates, yet their functional roles in insect reproduction remain poorly understood. Here, we identified two glycoprotein hormone subunits, SfLFT1 and SfLFT2, and their cognate receptor SfLFTR (a leucine-rich-repeat-containing GPCR) in Spodoptera frugiperda. Liposome-encapsulated siRNA-mediated knockdown of these genes severely disrupted ovarian development as evidenced by suppressed vitellogenin biosynthesis and reduced mature follicle formation. Coimmunoprecipitation and molecular docking analysis further demonstrated that SfLFT1 and SfLFT2 form a functional heterodimer that engages SfLFTR predominantly via SfLFT2. This interaction elevated intracellular cAMP levels, activating second-messenger signaling. RNAi-mediated silencing of the GnRH-related neuropeptides AKH, Crz, and ACP resulted in the downregulation of SfLFT1 and SfLFT2, collectively implying that these neuropeptides are upstream modulators of the thyrostimulin-like GPA2/GPB5 pathway. Our findings reveal a neuroendocrine cascade governing vitellogenesis and ovarian maturation in S. frugiperda, offering potential novel targets for pest management.