Insulin signaling pathways in lepidopteran ecdysone secretion

Abstract

Molting and metamorphosis are stimulated by the secretion of ecdysteroid hormones from the prothoracic glands. Insulin-like hormones have been found to enhance prothoracic gland activity, providing a mechanism to link molting to nutritional state. In silk moths (Bombyx mori), the prothoracic glands are directly stimulated by insulin and the insulin-like hormone bombyxin. Further, in Bombyx, the neuropeptide prothoracicotropic hormone (PTTH) appears to act at least in part through the insulin-signaling pathway. In the prothoracic glands of Manduca sexta, while insulin stimulates the phosphorylation of the insulin receptor and Akt, neither insulin nor bombyxin II stimulate ecdysone secretion. Involvement of the insulin-signaling pathway in Manduca prothoracic glands was explored using two inhibitors of phosphatidylinositol-3-kinase (PI3K), LY294002 and wortmannin. PI3K inhibitors block the phosphorylation of Akt and 4EBP but have no effect on ecdysone secretion, or on the phosphorylation of the MAPkinase, ERK. Inhibitors that block phosphorylation of ERK, including the MEK inhibitor U0126, and high doses of the RSK inhibitor SL0101, effectively inhibit ecdysone secretion. The results highlight differences between the two lepidopteran insects most commonly used to directly study ecdysteroid secretion. In Bombyx, the PTTH and insulin-signaling pathways intersect; both insulin and PTTH enhance the phosphorylation of Akt and stimulate ecdysteroid secretion, and inhibition of PI3K reduces ecdysteroid secretion. By contrast, in Manduca, the action of PTTH is distinct from insulin. The results highlight species differences in the roles of translational regulators such as 4EBP, and members of the MAPkinase pathway such as ERK and RSK, in the regulation of insect ecdysone secretion, and in the impact of nutritionally-sensitive hormones such as insulin in the control of ecdysone secretion and molting.

The Homeodomain Transcription Factors Antennapedia and POU-M2 Regulate the Transcription of the Steroidogenic Enzyme Gene Phantom in the Silkworm

“…Notably, the insect brain-derived neuropeptide prothoracicotropic hormone, together with bombyxins or other insulin-like peptides, acts on the PG and thus determines the timing of ecdysteroidogenesis and stimulates ecdysone secretion (1,(11)(12)(13)(14). TGF␤/activin and nitric oxide (NO) signals are also required for ecdysteroidogenesis in the PG (15,16).…”

Transcriptome profiling reveals mechanisms for the evolution of insect seasonality

“…AMPK is a member of the insulin, target of rapamycin (TOR) and cell death pathways (Kahn et al, 2005;Lippai et al, 2008), all of which are known to be important in the progression of development and molting in Lepidoptera (Lippai et al, 2008;Gu et al, 2009;Smith et al, 2014). In our transcriptome, Snf4Aγ was significantly downregulated in the later-emerging Z-strain compared with the earlier-emerging E-strain (FDR<0.001 on day 7) (Table 2; Fig.…”

A comprehensive study of the changes in ecdysteroid levels during the feeding phase of fifth instar larvae of the silkworm, Bombyx mori (Lepidoptera: Bombycidae)

“…In Drosophila, insulin/IGF signaling controls the basal levels of ecdysone synthesis in the PTG and transgene manipulations of the insulin producing cells (IPCs) reveals that an increase in insulin signaling causes an increase in ecdysteroidogenesis (Colombani et al, 2005;Walkiewicz & Stern, 2009). However, in M. sexta, insulin does not stimulate the PTG and increase ecdysone synthesis (Walsh & Smith, 2011;Smith et al, 2014). The reason for this discrepancy in the insulin-mediated ecdysteroidogenesis by the prothoracic gland is not clear (Smith et al, 2014).…”

“…However, in M. sexta, insulin does not stimulate the PTG and increase ecdysone synthesis (Walsh & Smith, 2011;Smith et al, 2014). The reason for this discrepancy in the insulin-mediated ecdysteroidogenesis by the prothoracic gland is not clear (Smith et al, 2014).…”

“…The increase in the level of ecdysteroid following the injection of insulin might be due to increased ecdysteroidogenesis by the PTG (Gu et al, 2009;Smith et al, 2014). In vitro studies on B. mori have revealed that insulin causes an increase in ecdysteroidogenesis in the PTG, but only when PTGs are isolated after day 4 of last instar larvae (Gu et al, 2009).…”