Prothoracicotropic hormone (PTTH) was first identified in the silk moth Bombyx mori where it regulates production and release of ecdysone (Ecd) in the prothoracic gland (Kataoka et al., 1991). The Bombyx PTTH is a homodimer of about 25 kDa where each monomer consists of 109 amino acids of which seven are cysteines. Six of these cysteines form three internal disulfide bridges in each monomer, and the seventh forms an intermolecular bridge to the other monomer (Kataoka et al., 1991). PTTH has been identified in several lepidopteran insects, and although the amino acid sequences are variable, the positions of the seven cysteines, and therefore the folding structure of the dimeric peptide, are well conserved (see Rybczynski, 2005; Marchal et al., 2009). The PTTH peptides are additionally characterized by several hydrophobic regions and a glycosylation site (see Marchal et al., 2009). The Drosophila PTTH precursor gene (CG13687), which was identified relatively late, can give rise to a peptide dimer very similar to that in lepidopterans (McBrayer et al., 2007). In Drosophila, the PTTH receptor is encoded on the gene torso (CG1389) and is a receptor tyrosine kinase (Rewitz et al., 2009).
PTTH seem to be exclusively distributed in 2 pairs of large neurosecretory cells in the pars lateralis of the brain in all studied insects (Nagasawa et al., 1986; Sauman and Reppert, 1996; McBrayer et al., 2007; Marchal et al., 2009). These neurons have axon terminations in the prothoracic glands. In Drosophila the torso receptor is expressed in the cells of the prothoracic gland and activation of torso phosphorylates extracellular signal regulated kinase, ERK (Rewitz et al., 2009).
In insects, the timing of molts and metamorphosis is coordinated by the circulating titer of the steroid hormone ecdysone (Gilbert et al., 2002). As the name indicates, PTTH regulates biosynthesis and maybe release of ecdysone in the prothoracic gland during development. In Drosophila, genetic ablation of the PTTH neurons does not affect adult emergence, but delayed development which resulted in bigger larvae, pupae and adults (Rewitz et al., 2009). This indicates that PTTH regulates developmental timing via ecdysone production, but the peptide is not necessary for normal ecdysis. A further layer in the regulation of ecdysone production was discovered recently. The insulin-like peptide 8 (DILP8) released from imaginal discs, and its receptor Lgr3 expressed on brain neurons are part of signal pathway that can regulate ecdysone production upon damage of disc tissues (Colombani et al., 2015; Vallejo et al., 2015). After activation by DILP8, the Lgr3 expressing brain interneurons, signal to the PTTH neurons and thus developmental timing can be correlated with growth of tissues. A recent finding is that cells of the prothoracic gland may release vesicular bound ecdysone in a calcium dependent manner in addition to the previously suggested diffusion through membranes (Yamanaka et al., 2016). Thus, there may be additional signals regulating ecdysone release.
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