New players in the regulation of ecdysone biosynthesis.
ABSTRACT Insect ecdysone steroid hormone regulates major developmental transitions, such as molting and metamorphosis. The production of ecdysone correlates well with the timing of these transitions. Finding out how the ecdysone biosynthesis is regulated is crucial to fully understand these sophisticated developmental switches. Here we summarized recent findings in the regulation of ecdysone biosynthesis from the aspects of cell signaling, key biosynthetic enzymes and substrate cholesterol trafficking.
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- "In most insects, ecdysteroids, and predominantly 20E, regulate moulting and metamorphosis, as well as some aspects of reproduction (Huang et al., 2008). Crustaceans also synthesize 20E along with ponasterone A (PoA, 25-deoxy-20E) (Lachaise & Lafont, 1984), and both have biological activity, although the role of PoA has not been studied as extensively as that of 20E (Mykles, 2011). "
ABSTRACT: The ecdysteroid biosynthetic pathway involves sequential enzymatic hydroxylations by a group of enzymes collectively known as Halloween gene proteins. Complete sequences for three Halloween genes, spook (Vdspo), disembodied (Vddib) and shade (Vdshd), were identified in varroa mites and sequenced. Phylogenetic analyses of predicted amino acid sequences for Halloween orthologues showed that the acarine orthologues were distantly associated with insect and crustacean clades indicating that acarine genes had more ancestral characters. The lack of orthologues or pseudogenes for remaining genes suggests these pathway elements had not evolved in ancestral arthropods. Vdspo transcript levels were highest in gut tissues, while Vddib transcript levels were highest in ovary-lyrate organs. In contrast, Vdshd transcript levels were lower overall but present in both gut and ovary-lyrate organs. All three transcripts were present in eggs removed from gravid female mites. A brood cell invasion assay was developed for acquiring synchronously staged mites. Mites within 4 h of entering a brood cell had transcript levels of all three that were not significantly different from mites on adult bees. These analyses suggest that varroa mites may be capable of modifying 7-dehydro-cholesterol precursor and hydroxylations of other steroid precursors, but whether the mites directly produce ecdysteroid precursors and products remains undetermined.Insect Molecular Biology 06/2015; 24(3). DOI:10.1111/imb.12155 · 2.98 Impact Factor
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- "The microsomal CYP306A was found to be responsible for C25 hydroxylation in Bombyx mori and D. melanogaster. The mitochondrial CYP314A1 converts E to 20E in the target tissues (Huang et al., 2008). Two other D. melanogaster CYPs which are related to ecdysteroid metabolism are the CYP18A1 responsible for the 26 carbon hydroxylation leading to the formation of 26,20E inactive hormone (Guittard et al., 2011) and CYP301A1 which was indicated to participate in a yet unclear mode in ecdysteroid metabolism or regulation in peripheral organs (Sztal et al., 2012). "
ABSTRACT: A transcriptomic assembly originated from hypodermis and Y organ of the crustacean Pontastacus leptodactylus is used here for in silico characterization of oxi-reductase enzymes potentially involved in the metabolism of ecdysteroid molting hormones. RNA samples were extracted from male Y organ and its neighboring hypodermis in all stages of the molt cycle. An equimolar RNA mix from all stages was sequenced using next generation sequencing technologies and de novo assembled, resulting with 74,877 unique contigs. These transcript sequences were annotated by examining their resemblance to all GenBank translated transcripts, determining their Gene Ontology terms and their characterizing domains. Based on the present knowledge of arthropod ecdysteroid metabolism and more generally on steroid metabolism in other taxa, transcripts potentially related to ecdysteroid metabolism were identified and their longest possible conceptual protein sequences were constructed in two stages, correct reading frame was deduced from BLASTX resemblances, followed by elongation of the protein sequence by identifying the correct translation frame of the original transcript. The analyzed genes belonged to several oxi-reductase superfamilies including the Rieske non heme iron oxygenases, cytochrome P450s, short-chained hydroxysteroid oxi-reductases, aldo/keto oxireductases, lamin B receptor/sterol reductases and glucose-methanol-cholin oxi-reductatses. A total of 68 proteins were characterized and the most probable participants in the ecdysteroid metabolism where indicated. The study provides transcript and protein structural information, a starting point for further functional studies, using a variety of gene-specific methods to demonstrate or disprove the roles of these proteins in relation to ecdysteroid metabolism in P. leptodactylus.General and Comparative Endocrinology 09/2013; DOI:10.1016/j.ygcen.2013.09.003 · 2.67 Impact Factor
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- "The acute effects of prothoracicotropic or prothoracicostatic factors which becomes manifest temporally during short-term in vitro incubation of the PG are mediated by translation and phosphorylation of intercellular molecules involved in the signal transduction of ecdysteroidogenesis (Gilbert et al., 2002; Huang et al., 2008; Rewitz et al., 2009a). On the other hand, the chronic effects of these factors which become obvious on a longer time scale during development are mediated by the transcriptional regulation of some genes encoding ecdysteroidogenic enzymes probably via cAMP-mediated pathway (Gilbert et al., 2002; Huang et al., 2008). The chronic effects of these factors are pharmacologically separable from the acute effects (Yamanaka et al., 2007). "
ABSTRACT: Molting and metamorphosis are strictly regulated by steroid hormones known as ecdysteroids. It is now widely recognized that ecdysteroid biosynthesis (ecdysteroidogenesis) in the prothoracic gland (PG) is regulated by the tropic factor prothoracicotropic hormone (PTTH). However, the importance of PTTH in the induction of molting and metamorphosis remains unclear, and other mechanisms are thought to be involved in the regulation of ecdysteroidogenesis by the PG. Recently, new regulatory mechanisms, prothoracicostatic factors, and neural regulation have been explored using the silkworm, Bombyx mori, and two circulating prothoracicostatic factors, prothoracicostatic peptide (PTSP) and Bommo-myosuppressin (BMS), have been identified. Whereas PTTH and BMS are secreted from the brain, PTSP is secreted from the peripheral neurosecretory system - the epiproctodeal gland - during the molting stage. The molecular basis of neural regulation of ecdysteroidogenesis has been revealed for the first time in B. mori. The innervating neurons supply both Bommo-FMRF related peptide (BRFa) and orcokinin to maintain low levels of ecdysteroids during the feeding stage. These complex regulatory mechanisms - involving tropic and static factors, peripheral neurosecretory cells as well as the central neuroendocrine system, and neural regulation in addition to circulating factors collaborate to regulate ecdysteroidogenesis. Thus, together they create the finely tuned fluctuations in ecdysteroid titers needed in the hemolymph during insect development.Frontiers in Endocrinology 12/2011; 2:107. DOI:10.3389/fendo.2011.00107