Ecdysteroid hormone action

Spindler, Klaus-Dieter; Honl, Celine; Tremmel, Ch.; Braun, Simone; Ruff, Heike; Spindler-Barth, Margarethe

doi:10.1007/s00018-009-0112-5

Cited by 103 publications

(74 citation statements)

References 139 publications

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“…In insects and other arthropods, steroid hormones designated as ecdysteroids, such as ecdysone and its derivative, 20-hydroxyecdysone (20E), control the precise temporal progression of development (Thummel, 2001;Gilbert et al, 2002;Mirth and Riddiford, 2007;Spindler et al, 2009). Ecdysone is synthesized via a series of hydroxylation and oxidation steps in the prothoracic gland (PG) during postembryonic development and in the ovary in adults .…”

Section: Introductionmentioning

confidence: 99%

Non-molting glossy/shroud encodes a short-chain dehydrogenase/reductase that functions in the ‘Black Box’ of the ecdysteroid biosynthesis pathway

et al. 2010

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SUMMARYIn insects, the precise timing of molting and metamorphosis is strictly guided by a principal steroid hormone, ecdysone. Among the multiple conversion steps for synthesizing ecdysone from dietary cholesterol, the conversion of 7-dehydrocholesterol to 5-ketodiol, the so-called 'Black Box', is thought to be the important rate-limiting step. Although a number of genes essential for ecdysone synthesis have recently been revealed, much less is known about the genes that are crucial for functioning in the Black Box. Here we report on a novel ecdysteroidgenic gene, non-molting glossy (nm-g)/shroud (sro), which encodes a short-chain dehydrogenase/reductase. This gene was first isolated by positional cloning of the nm-g mutant of the silkworm Bombyx mori, which exhibits a low ecdysteroid titer and consequently causes a larval arrest phenotype. In the fruit fly, Drosophila melanogaster, the closest gene to nm-g is encoded by the sro locus, one of the Halloween mutant members that are characterized by embryonic ecdysone deficiency. The lethality of the sro mutant is rescued by the overexpression of either sro or nm-g genes, indicating that these two genes are orthologous. Both the nm-g and the sro genes are predominantly expressed in tissues producing ecdysone, such as the prothoracic glands and the ovaries. Furthermore, the phenotypes caused by the loss of function of these genes are restored by the application of ecdysteroids and their precursor 5-ketodiol, but not by cholesterol or 7-dehydrocholesterol. Altogether, we conclude that the Nm-g/Sro family protein is an essential enzyme for ecdysteroidogenesis working in the Black Box.

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Section: Introductionmentioning

confidence: 99%

Non-molting glossy/shroud encodes a short-chain dehydrogenase/reductase that functions in the ‘Black Box’ of the ecdysteroid biosynthesis pathway

et al. 2010

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“…However, the molecular mechanisms of cholesterol metabolism in these ecdysozoan animals have not been fully elucidated. The principal steroid hormones in nematodes and arthropods are dafachronic acids and ecdysteroids, respectively, both of which play pivotal roles in the regulation of developmental timing, reproduction, and longevity (1,7,8). In the biosynthesis of both dafachronic acids and ecdysteroids, which is different from the biosynthesis of vertebrate steroid hormones, cholesterol is converted to 7-dehydrocholesterol (7dC) 5 by dehydrogenation of the carbons at positions 7 and 8 ( Fig.…”

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confidence: 99%

The Conserved Rieske Oxygenase DAF-36/Neverland Is a Novel Cholesterol-metabolizing Enzyme

Yoshiyama-Yanagawa

Enya

Shimada-Niwa

et al. 2011

Journal of Biological Chemistry

149

118

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Steroid hormones play essential roles in a wide variety of biological processes in multicellular organisms. The principal steroid hormones in nematodes and arthropods are dafachronic acids and ecdysteroids, respectively, both of which are synthesized from cholesterol as an indispensable precursor. The first critical catalytic step in the biosynthesis of these ecdysozoan steroids is the conversion of cholesterol to 7-dehydrocholesterol. However, the enzymes responsible for cholesterol 7,8-dehydrogenation remain unclear at the molecular level. Here we report that the Rieske oxygenase DAF-36/Neverland (Nvd) is a cholesterol 7,8-dehydrogenase. The daf-36/nvd genes are evolutionarily conserved, not only in nematodes and insects but also in deuterostome species that do not produce dafachronic acids or ecdysteroids, including the sea urchin Hemicentrotus pulcherrimus, the sea squirt Ciona intestinalis, the fish Danio rerio, and the frog Xenopus laevis. An in vitro enzymatic assay system reveals that all DAF-36/Nvd proteins cloned so far have the ability to convert cholesterol to 7-dehydrocholesterol. Moreover, the lethality of loss of nvd function in the fruit fly Drosophila melanogaster is rescued by the expression of daf-36/ nvd genes from the nematode Caenorhabditis elegans, the insect Bombyx mori, or the vertebrates D. rerio and X. laevis. These data suggest that daf-36/nvd genes are functionally orthologous across the bilaterian phylogeny. We propose that the daf-36/nvd family of proteins is a novel conserved player in cholesterol metabolism across the animal phyla.Steroid hormones are crucial for development, growth, and homeostasis in multicellular organisms. Cholesterol and other sterol(s) serve as indispensable precursors for the biosynthesis of steroid hormones, and the conversion of cholesterol to the next specific intermediate is a crucial biochemical step across species (1-4). In the biosynthesis of vertebrate steroid hormones, cholesterol is commonly converted to pregnenolone by side-chain cleavage catalyzed by the cytochrome P450 monooxygenase P450scc/CYP11A1 (2). The step catalyzed by CYP11A1 is the key rate-limiting step in the synthesis of all vertebrate steroids, and it thus is controlled by numerous physiological responses throughout the life cycle (2, 5).Cholesterol is also required for steroid hormone biosynthesis in protostomes, including nematodes and arthropods (1, 6). However, the molecular mechanisms of cholesterol metabolism in these ecdysozoan animals have not been fully elucidated. The principal steroid hormones in nematodes and arthropods are dafachronic acids and ecdysteroids, respectively, both of which play pivotal roles in the regulation of developmental timing, reproduction, and longevity (1,7,8). In the biosynthesis of both dafachronic acids and ecdysteroids, which is different from the biosynthesis of vertebrate steroid hormones, cholesterol is converted to 7-dehydrocholesterol (7dC) 5 by dehydrogenation of the carbons at positions 7 and 8 (Fig. 1A) (9). Nematodes and arthropods lo...

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“…Some possess metal-like conductivity due to π-electrons, others not. Probably, these different chemical properties not only facilitate diverse interactions with proteins (Doukas, 1975) but may facilitate also crosstalk-like actions between hormones (Pieterse et al, 2009;Spindler et al, 2009).…”

Section: Hormones and Neurotransmittersmentioning

confidence: 99%

Low-molecular-weight metabolite systems chemistry

Hadaček

Bachmann

2015

Front. Environ. Sci.

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Low-molecular-weight metabolites (LMWMs) comprise primary or central and a plethora of intermediary or secondary metabolites, all of which are characterized by a molecular weight below 900 Dalton. The latter are especially prominent in sessile higher organisms, such as plants, corals, sponges and fungi, but are produced by all types of microbial organisms too. Common to all of these carbon molecules are oxygen, nitrogen and, to a lesser extent, sulfur, as heteroatoms. The latter can contribute as electron donators or acceptors to cellular redox chemistry and define the potential of the molecule to enter charge-transfer complexes. Furthermore, they allow LMWMs to serve as organic ligands in coordination complexes with various inorganic metals as central atoms. Especially the transition metals Fe, Cu, and Mn can catalyze one electron reduction of molecular oxygen, which results in formation of free radical species and reactive follow-up reaction products. As antioxidants LMWMs can scavenge free radicals. Depending on the chemical environment, the same LMWMs can act as pro-oxidants by reducing molecular oxygen. The cellular regulation of redox homeostasis, a balance between oxidation and reduction, is still far from being understood. Charge-transfer and coordination complex formation with metals shapes LMWMs into gel-like matrices in the cytosol. The quasi-polymer structure is lost usually during the isolation procedure. In the gel state, LMWMs possess semiconductor properties. Also proteins and membranes are semiconductors. Together they can represent biotransistor components that can be part of a chemoelectrical signaling system that coordinates systems chemistry by initiating cell differentiation or tissue homeostasis, the activated and the resting cell state, when it is required. This concept is not new and dates back to Albert Szent-Györgyi.

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Ecdysteroid hormone action

Cited by 103 publications

References 139 publications

Non-molting glossy/shroud encodes a short-chain dehydrogenase/reductase that functions in the ‘Black Box’ of the ecdysteroid biosynthesis pathway

Non-molting glossy/shroud encodes a short-chain dehydrogenase/reductase that functions in the ‘Black Box’ of the ecdysteroid biosynthesis pathway

The Conserved Rieske Oxygenase DAF-36/Neverland Is a Novel Cholesterol-metabolizing Enzyme

Low-molecular-weight metabolite systems chemistry

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