Cited by 532Neurobiology and Insect Physiology ResearchSteroid Chemistry and BiochemistryLipid metabolism and biosynthesis

The DOI matches its Crossref record; 185 of the 185 references it cites were found in a registry or an index.

Control and Biochemical Nature of the Ecdysteroidogenic Pathway

Gilbert, Lawrence I., Rybczynski, Robert, Warren, James T.·2002·Annual Review of Entomology

DOI 10.1146/annurev.ento.47.091201.145302

Open this paper in CoChat — free account

Abstract

Molting is elicited by a critical titer of ecdysteroids that includes the principal molting hormone, 20-hydroxyecdysone (20E), and ecdysone (E), which is the precursor of 20E but also has morphogenetic roles of its own. The prothoracic glands are the predominate source of ecdysteroids, and the rate of synthesis of these polyhydroxylated sterols is critical for molting and metamorphosis. This review concerns three aspects of ecdysteroidogenesis: (a) how the brain neuropeptide prothoracicotropic hormone (PTTH) initiates a transductory cascade in cells of the prothoracic gland, which results in an increased rate of ecdysteroid biosynthesis (upregulation); (b) how the concentrations of 20E in the hemolymph feed back on the prothoracic gland to decrease rates of ecdysteroidogenesis (downregulation); and (c) how the prothoracic gland cells convert cholesterol to the precursor of E and then 20E, a series of reactions only now being understood because of the use of a combination of classical biochemistry and molecular genetics.

Integrity signals

Registry

Crossref · 10.1146/annurev.ento.47.091201.145302

Cites

185 of 185 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The Steroid and Thyroid Hormone Receptor Superfamily
Evans, R. M. (1988) · Science · doi:10.1126/science.3283939 · Cited by 7,394
Comprehensive insect physiology, biochemistry and pharmacology
(1985) · Journal of Insect Physiology · doi:10.1016/0022-1910(85)90117-9 · Cited by 4,819
Steroid Receptor Interactions with Heat Shock Protein and Immunophilin Chaperones*
Pratt, W. B., & Toft, D. O. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.3.0303 · Cited by 1,791
Signal Transduction through MAP Kinase Cascades
Lewis, T. S., Shapiro, P. S., & Ahn, N. G. (1998) · Advances in cancer research · doi:10.1016/s0065-230x(08)60765-4 · Cited by 1,759
Evidence for a clade of nematodes, arthropods and other moulting animals
Aguinaldo, A. M. A., Turbeville, J. M., Linford, L. S., Rivera, M. C., Garey, J. R., Raff, R. A., & Lake, J. A. (1997) · Nature · doi:10.1038/387489a0 · Cited by 1,609
Comprehensive insect physiology, biochemistry and pharmacology
Brooks, G. T. (1985) · Insect Biochemistry · doi:10.1016/0020-1790(85)90131-3 · Cited by 1,595
Mutations affecting the pattern of the larval cuticle inDrosophila melanogaster
N�sslein-Volhard, C., Wieschaus, E. F., & Kluding, H. (1984) · Development Genes and Evolution · doi:10.1007/bf00848156 · Cited by 1,552
A Family of cAMP-Binding Proteins That Directly Activate Rap1
Kawasaki, H., Springett, G. M., Mochizuki, N., Toki, S., Nakaya, M., Matsuda, M., Housman, D. E., & Graybiel, A. M. (1998) · Science · doi:10.1126/science.282.5397.2275 · Cited by 1,386
Regulation of the acute production of steroids in steroidogenic cells
STOCCO, D. M., & CLARK, B. J. (1996) · Endocrine Reviews · doi:10.1210/edrv-17-3-221 · Cited by 1,057
The drosophila EcR gene encodes an ecdysone receptor, a new member of the steroid receptor superfamily
Koelle, M. R., Talbot, W. S., Segraves, W. A., Bender, M. T., Cherbas, P. T., & Hogness, D. S. (1991) · Cell · doi:10.1016/0092-8674(91)90572-g · Cited by 966

Show all 185 references

Research works printed but not linked: 14

Bergamasco R, Horn DHS. 1980. The biological activities of ecdysteroids and ecdysteroid analogues. In Progress in Ecdysone Research , ed. JA Hoffmann, 7:299–324. Amsterdam/New York/Oxford: Elsevier/North Holland Biomed.
Böcking D, 1994, C. R. Acad. Sci. Paris, 317, 891
10.1210/me.9.11.1549 · DOI
10.1210/me.8.12.1731 · DOI
Fujimoto Y, 2000, AOCS Press, 35, 279
Gelman DB, 1995, Eur. J. Entomol., 92, 123
Gilbert LI, 1967, Adv. Insect Physiol., 4, 169
Ishizaki H, 1994, Int. J. Dev., 38, 301
Kappler C, Hetru C, Durst F, Hoffmann JA. 1989. Enzymes involved in ecdysone biosynthesis. In Ecdysone: From Chemistry to Mode of Action , ed. J Koolman, pp. 161–66. Stuttgart: Georg Thieme-Verlag
10.1210/me.9.7.838 · DOI
Nakanishi K, 1966, J. Chem. Soc. Chem. Commun., 915
Rees HH, 1995, Eur. J. Entomol., 92, 9
Rybczynski R, 2001, Mol. Cell. Endocrinol.
Smith WA, 1997, Arch. Insect Biochem. Physiol., 30, 579

Sorted by citations

Nutrient-Dependent Expression of Insulin-like Peptides from Neuroendocrine Cells in the CNS Contributes to Growth Regulation in Drosophila
Ikeya, T., Galic, M., Belawat, P., Nairz, K., & Hafen, E. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01043-6 · Cited by 765
Nuclear receptors — a perspective from Drosophila
King‐Jones, K., & Thummel, C. S. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1581 · Cited by 587
“ECDYSTEROIDS are produced by the PROTHORACIC GLANDS and released into the HAEMOLYMPH , primarily as α-ecdysone (αE), which is then converted by peripheral tissues to the biologically active form, 20E (Ref”
Method
Insights into the molecular basis of the hormonal control of molting and metamorphosis from Manduca sexta and Drosophila melanogaster
Riddiford, L. M., Hiruma, K., Zhou, X., & Nelson, C. A. (2003) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2003.06.001 · Cited by 547
Drosophila neuropeptides in regulation of physiology and behavior
Nässel, D. R., & Winther, Å. M. E. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.04.010 · Cited by 498
Shade is the Drosophila P450 enzyme that mediates the hydroxylation of ecdysone to the steroid insect molting hormone 20-hydroxyecdysone
Petryk, A., Warren, J. T., Marqués, G., Jarcho, M. P., Gilbert, L. I., Kahler, J. L., Parvy, J.-P., Li, Y., Dauphin‐Villemant, C., & O’Connor, M. B. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2336088100 · Cited by 493
Diabetic Larvae and Obese Flies—Emerging Studies of Metabolism in Drosophila
Baker, K. D., & Thummel, C. S. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.09.002 · Cited by 467
“A key difference between mammalian and insect metabolism is the inability of insects to synthesize cholesterol, rendering them cholesterol auxotrophs (Gilbert et al., 2002).”
Background
Size assessment and growth control: how adult size is determined in insects
Mirth, C. K., & Riddiford, L. M. (2007) · BioEssays · doi:10.1002/bies.20552 · Cited by 454
“This then induces ecdysone secretion, which initiates the cessation of feeding and onset of wandering behavior.((58))”
Background
The Insect Neuropeptide PTTH Activates Receptor Tyrosine Kinase Torso to Initiate Metamorphosis
Rewitz, K., Yamanaka, N., Gilbert, L. I., & O’Connor, M. B. (2009) · Science · doi:10.1126/science.1176450 · Cited by 367
Hormonal cross talk in insect development
Dubrovsky, E. B. (2004) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2004.11.003 · Cited by 362
Recent advances in neuropeptide signaling in Drosophila, from genes to physiology and behavior
Nässel, D. R., & Zandawala, M. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.02.003 · Cited by 373
“Functions: The timing of molts and metamorphosis in insects is coordinated by the steroid hormone ecdysone (Gilbert et al., 2002).”
Molecular and biochemical characterization of two P450 enzymes in the ecdysteroidogenic pathway of Drosophila melanogaster
Warren, J. T., Petryk, A., Marqués, G., Jarcho, M. P., Parvy, J.-P., Dauphin‐Villemant, C., O’Connor, M. B., & Gilbert, L. I. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162375799 · Cited by 335
Spook and Spookier code for stage-specific components of the ecdysone biosynthetic pathway in Diptera
Ono, H., Rewitz, K., Shinoda, T., Itoyama, K., Petryk, A., Rybczynski, R., Jarcho, M. P., Warren, J. T., Marqués, G., Shimell, M., et al. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.07.023 · Cited by 334
“Since the Black Box is presently thought to represent several oxidative transformations involved in the conversion of 7dC to the Δ(4)-diketol (Gilbert et al., 2002), unless Spo catalyzes the initial reaction, then expressing Spo alone with 7dC would not be expected to produce a product.”
Background
Hormonal Control of Reproductive Processes
Raikhel, A. S., Brown, M. R., & Bellés, X. (2005) · Elsevier eBooks · doi:10.1016/b0-44-451924-6/00040-5 · Cited by 323
“The disembodied, shadow, phantom, and shade genes encode cytochrome P450 enzymes involved in the final hydroxylation steps of ecdysteroid biosynthesis (Gilbert et al., 2002; Warren et al., 2002; Petryk et al., 2003) (see Chapter 3.3 for details).”
BackgroundInfluential
Cross-induction of detoxification genes by environmental xenobiotics and insecticides in the mosquito Aedes aegypti: Impact on larval tolerance to chemical insecticides
Poupardin, R., Reynaud, S., Strode, C., Ranson, H., VONTAS, J. G., & David, J. (2008) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2008.01.004 · Cited by 317
“Other regulatory elements such as the ecdysone response element (EcRE) (Gilbert et al., 2002), the constitutive androstane receptor family (CAR) (King-Jones et al., 2006) and the antioxidant response element (ARE) (Li et al., 2002) have been involved in insect response to xenobiotics and may…”
Background
CYP306A1, a Cytochrome P450 Enzyme, Is Essential for Ecdysteroid Biosynthesis in the Prothoracic Glands of Bombyx and Drosophila
Niwa, R., Matsuda, T., Yoshiyama, T., Namiki, T., Mita, K., Fujimoto, Y., & Kataoka, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404514200 · Cited by 319
Halloween genes encode P450 enzymes that mediate steroid hormone biosynthesis in Drosophila melanogaster
Gilbert, L. I. (2004) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2003.11.003 · Cited by 300
“Actually, the major molting hormone of insects is 20-hydroxyecdysone although ecdysone appears to have roles of its own in addition to being the immediate precursor of 20-hydroxyecdysone (Gilbert et al., 2002).”
Background
Functional Genomic Analysis of C. elegans Molting
Frand, A. R., Russel, S., & Ruvkun, G. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030312 · Cited by 300
“Production of a ligand for NHR-23 is likely to be tightly regulated, similar to how steroidogenesis in the prothoracic gland of insects is induced by the neuropeptide prothoracicotropic hormone but also repressed by ecdysteroids [3,70].”
Background
Phantom encodes the 25-hydroxylase of Drosophila melanogaster and Bombyx mori: a P450 enzyme critical in ecdysone biosynthesis
Warren, J. T., Petryk, A., Marqués, G., Parvy, J.-P., Shinoda, T., Itoyama, K., Kobayashi, J., Jarcho, M. P., Li, Y., O’Connor, M. B., et al. (2004) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2004.06.009 · Cited by 296
The TOR Pathway Couples Nutrition and Developmental Timing in Drosophila
Layalle, S., Arquier, N., & Léopold, P. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.08.003 · Cited by 295
“No bona fide PTTH receptor is identified yet, and the previously identified response to PTTH is a rise in cAMP, leading to a cascade of activation of kinases, including PKA, MAPKs, PKC, and S6-kinase (Gilbert et al., 2002; Rybczynski, 2005; Rybczynski and Gilbert, 2006).”
Background
Direct effect of acaricides on pathogen loads and gene expression levels in honey bees Apis mellifera
Boncristiani, H., Underwood, R. M., Schwarz, R. S., Evans, J. D., Pettis, J. S., & vanEngelsdorp, D. (2011) · Journal of Insect Physiology · doi:10.1016/j.jinsphys.2011.12.011 · Cited by 284
“Protein kinase pathways are responsible for ecdysteroid synthesis control from dietary cholesterol or phytosterols via a series of hydroxylation steps (Thummel and Chory, 2002; Gilbert et al., 2011).”
Background
Insect Sterol Nutrition and Physiology: A Global Overview
Behmer, S. T., & Nes, W. D. (2003) · Advances in insect physiology · doi:10.1016/s0065-2806(03)31001-x · Cited by 281
Ras Activity in the Drosophila Prothoracic Gland Regulates Body Size and Developmental Rate via Ecdysone Release
Caldwell, P. E., Walkiewicz, M. A., & Stern, M. (2005) · Current Biology · doi:10.1016/j.cub.2005.09.011 · Cited by 274
Arthropod nuclear receptors and their role in molting
Nakagawa, Y., & Henrich, V. C. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.07347.x · Cited by 259
Structural adaptability in the ligand-binding pocket of the ecdysone hormone receptor
Billas, I. M. L., Iwema, T., Garnier, J., Mitschler, A., Rochel, N., & Moras, D. (2003) · Nature · doi:10.1038/nature02112 · Cited by 254
“The key hormone for the development of most insects is 20-hydroxyecdysone (20E), but experimental evidence indicates that ecdysone and other ecdysteroids coexist with 20E and have distinct roles at different insect developmental stage”
Background
Enzymes for ecdysteroid biosynthesis: Their biological functions in insects and beyond
Niwa, R., & Niwa, Y. S. (2014) · Bioscience, Biotechnology, and Biochemistry · doi:10.1080/09168451.2014.942250 · Cited by 249
Neverland is an evolutionally conserved Rieske-domain protein that is essential for ecdysone synthesis and insect growth
Yoshiyama, T., Namiki, T., Mita, K., Kataoka, H., & Niwa, R. (2006) · Development · doi:10.1242/dev.02428 · Cited by 250
“The nurse cells are considered to be the source of ecdysteroids in adult females (Riddiford, 1993; Gilbert et al., 2002) and a number of ecdysteroidogenic genes, such as dare, Start1 and ecdysoneless, are known to be expressed in the nurse cells (Freeman et al.”
BackgroundMethodInfluential
The Drosophila Orphan Nuclear Receptor DHR38 Mediates an Atypical Ecdysteroid Signaling Pathway
Baker, K. D., Shewchuk, L. M., Kozlova, T., Makishima, M., Hassell, A. M., Wisely, B., Caravella, J. A., Lambert, M. H., Reinking, J. L., Krause, H. M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00420-3 · Cited by 238
“…(20E) in the peripheral tissues Research Triangle Park, North Carolina 27709 is thought to elicit most of the effects of ecdysteroid 3 Howard Hughes Medical Institute and pulses, with the remaining metabolites having no known Department of Human Genetics function (Gilbert et al., 2002).”
Background
Four-way regulation of mosquito yolk protein precursor genes by juvenile hormone-, ecdysone-, nutrient-, and insulin-like peptide signaling pathways
Hansen, I. A., Attardo, G. M., Rodriguez, S. D., & Drake, L. L. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00103 · Cited by 198
“During larval development a peptide hormone, prothoracicotropic hormone (PTTH), is released from the brain and stimulates ecdysone synthesis in the prothoracic gland by activating the RAS/ERK pathway (Gilbert et al., 2002; Rewitz et al., 2009).”
Background
Marine invertebrate cytochrome P450: Emerging insights from vertebrate and insect analogies
Rewitz, K., Styrishave, B., Løbner‐Olesen, A., & Andersen, O. (2006) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2006.04.001 · Cited by 199
“Since the biosynthetic pathways are similar in crustaceans and insects (Lachaise et al., 1993; Gilbert et al., 2002), it is reasonable to assume that crustaceans may possess orthologs of the insect Halloween genes.”
Background
Multifaceted biological insights from a draft genome sequence of the tobacco hornworm moth, Manduca sexta
Kanost, M. R., Arrese, E. L., Cao, X., Chen, Y.-R., Chellapilla, S., Goldsmith, M. R., Große‐Wilde, E., Heckel, D. G., Herndon, N., Jiang, H., et al. (2016) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2016.07.005 · Cited by 197
“It is an important model species for investigations of development and metamorphosis (Gilbert et al., 2002; Hiruma and Riddiford, 2010; Nijhout et al., 2014; Truman et al., 2006; Truman and Riddiford, 2007), neurobiology and olfaction (Heinbockel et al.”
Neuroendocrine regulation of Drosophila metamorphosis requires TGFβ/Activin signaling
Gibbens, Y., Warren, J. T., Gilbert, L. I., & O’Connor, M. B. (2011) · Development · doi:10.1242/dev.063412 · Cited by 198
“(Mauras et al., 1996; Sisk and Foster, 2004; Gilbert et al., 1997; Gilbert et al., 2002).”
BackgroundMethod
Nutritional control of body size through FoxO-Ultraspiracle mediated ecdysone biosynthesis
Koyama, T., Rodrigues, M. A., Athanasiadis, A., Shingleton, A. W., & Mirth, C. K. (2014) · eLife · doi:10.7554/elife.03091 · Cited by 184
“Since many CYP450 enzymes are involved in ecdysone biosynthesis (Gilbert et al., 2002), this led us to the hypothesis that the effect of IIS/TOR signaling on ecdysone biosynthesis is mediated by the interaction between FoxO and either EcR or Usp.”
Background
Independent elaboration of steroid hormone signaling pathways in metazoans
Markov, G. V., Tavares, R., Dauphin-Villemant, C., Demeneix, B. A., Baker, M. E., & Laudet, V. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812138106 · Cited by 187
Dilp8 requires the neuronal relaxin receptor Lgr3 to couple growth to developmental timing
Garelli, A., Herédia, F., Casimiro, A. P., Macedo, A., Nunes, C., Garcez, M., Dias, A. R. M., Volonté, Y., Uhlmann, T., Caparrós, E., et al. (2015) · Nature Communications · doi:10.1038/ncomms9732 · Cited by 190
Cholesterol in health and disease
Tabas, I. A. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0216381 · Cited by 190
Cytochrome P450 CYP307A1/Spook: A regulator for ecdysone synthesis in insects
Namiki, T., Niwa, R., Sakudoh, T., Shirai, K.-I., Takeuchi, H., & Kataoka, H. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.09.043 · Cited by 189
Non-molting glossy / shroud encodes a short-chain dehydrogenase/reductase that functions in the ‘Black Box’ of the ecdysteroid biosynthesis pathway
Niwa, R., Namiki, T., Ito, K., Shimada‐Niwa, Y., Kiuchi, M., Kawaoka, S., Kayukawa, T., Banno, Y., Fujimoto, Y., Shigenobu, S., et al. (2010) · Development · doi:10.1242/dev.045641 · Cited by 185
“…Satoru Kobayashi7, Toru Shimada4, Susumu Katsuma4 and Tetsuro Shinoda3,† D E V E LO P M E N T 1992 2002) and is ultimately under the regulation of the neuropeptide prothoracicotropic hormone (PTTH) and a subsequent intracellular signaling pathway (Gilbert et al., 2002; Rewitz et al., 2009).”
BackgroundInfluential
Integrating Body and Organ Size in Drosophila: Recent Advances and Outstanding Problems
Mirth, C. K., & Shingleton, A. W. (2012) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00049 · Cited by 180
“PTTH in turn stimulates the prothoracic gland to produce ecdysone (Dominick and Truman, 1985; Gilbert et al., 2002).”
Background
The Halloween genes code for cytochrome P450 enzymes mediating synthesis of the insect moulting hormone
Rewitz, K., Rybczynski, R., Warren, J. T., & Gilbert, L. I. (2006) · Biochemical Society Transactions · doi:10.1042/bst0341256 · Cited by 179
Genomics and Peptidomics of Neuropeptides and Protein Hormones Present in the Parasitic Wasp Nasonia vitripennis
Hauser, F., Neupert, S., Williamson, M. P., Predel, R., Tanaka, Y., & Grimmelikhuijzen, C. J. P. (2010) · Journal of Proteome Research · doi:10.1021/pr100570j · Cited by 176
Regulation of Body Size and Growth Control
Texada, M. J., Koyama, T., & Rewitz, K. (2020) · Genetics · doi:10.1534/genetics.120.303095 · Cited by 177
The Conserved Rieske Oxygenase DAF-36/Neverland Is a Novel Cholesterol-metabolizing Enzyme
Yoshiyama, T., Enya, S., Shimada‐Niwa, Y., Yaguchi, S., Haramoto, Y., Matsuya, T., Shiomi, K., Sasakura, Y., Takahashi, S., Asashima, M., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.244384 · Cited by 175
Molecular characterization of prothoracicotropic hormone and diapause hormone in Heliothis virescens during diapause, and a new role for diapause hormone
Xu, W. ‐., & Denlinger, D. L. (2003) · Insect Molecular Biology · doi:10.1046/j.1365-2583.2003.00437.x · Cited by 174
“The detection of Hvi-PTTH mRNA in the brain using Northern blotting is consistent with the brain being the primary site of PTTH synthesis in Lepidoptera (AdachiYamada et al., 1994; Gilbert et al., 2002).”
Method
Circadian Control of Eclosion
Myers, E. M., Yu, J., & Sehgal, A. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00167-2 · Cited by 171
Ecdysteroid Chemistry and Biochemistry
Lafont, R., Dauphin‐Villemant, C., Warren, J. T., & Rees, H. H. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-384749-2.10004-4 · Cited by 176
Cholesterol in health and disease
Tabas, I. A. (2002) · Journal of Clinical Investigation · doi:10.1172/jci16381 · Cited by 167
Steroid signaling in plants and insects—common themes, different pathways
Thummel, C. S., & Chory, J. (2002) · Genes & Development · doi:10.1101/gad.1042102 · Cited by 161
“It has been proposed that the translocation of 7-dehydrocholesterol from the endoplasmic reticulum to the mitochondria, where it may be oxidized to downstream steps in the pathway, is a rate-limiting step in ecdysteroid biosynthesis (Gilbert et al. 2002).”
BackgroundInfluential
Metabolism and growth adaptation to environmental conditions in Drosophila
Koyama, T., Texada, M. J., Halberg, K. A., & Rewitz, K. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03547-2 · Cited by 152
Drosophila Niemann-Pick Type C-2 genes control sterol homeostasis and steroid biosynthesis: a model of human neurodegenerative disease
Huang, X., Warren, J. T., Buchanan, J., Gilbert, L. I., & Scott, M. P. (2007) · Development · doi:10.1242/dev.004572 · Cited by 158
“The regulation of ecdysteroid biosynthesis and the downstream events that mediate ecdysteroid hormone action have been studied continuously for several decades using genetic and biochemical approaches (Gilbert et al., 2002).”
Background
Modeling metabolic homeostasis and nutrient sensing in Drosophila: implications for aging and metabolic diseases
Owusu-Ansah, E., & Perrimon, N. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.012989 · Cited by 156
“Similar concerns arise over the fact that flies are unable to synthesize cholesterol (Gilbert et al., 2002).”
Background
A role for βFTZ-F1 in regulating ecdysteroid titers during post-embryonic development in Drosophila melanogaster
Parvy, J.-P., Blais, C., Bernard, F., Warren, J. T., Petryk, A., Gilbert, L. I., O’Connor, M. B., & Dauphin‐Villemant, C. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2005.02.028 · Cited by 149
A Drosophila model of the Niemann-Pick type C lysosome storage disease: dnpc1a is required for molting and sterol homeostasis
Huang, X., Suyama, K. L., Buchanan, J., Zhu, A. J., & Scott, M. P. (2005) · Development · doi:10.1242/dev.02079 · Cited by 149
“High cholesterol or 7-dehydrocholesterol in the medium rescues dnpc1a mutants For insect ecdysone biosynthesis, the substrate cholesterol is first converted to 7-dehydrocholesterol, probably by a microsomal/endoplasmic reticulum (ER)-localized P450 enzyme (Gilbert et al., 2002).”
BackgroundInfluential
Control of ecdysteroidogenesis in prothoracic glands of insects: A review
Marchal, E., Vandersmissen, H. P., Badisco, L., de Velde, S. V., Verlinden, H., Iga, M., Wielendaele, P. V., Huybrechts, R., Simonet, G., Smagghe, G. J., et al. (2009) · Peptides · doi:10.1016/j.peptides.2009.08.020 · Cited by 148
“[39]; Rybczynski [97]; Huang et al.”
Background
Developmental Checkpoints and Feedback Circuits Time Insect Maturation
Rewitz, K., Yamanaka, N., & O’Connor, M. B. (2013) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-385979-2.00001-0 · Cited by 143
“This idea is consistent with studies showing that ecdysone inhibits ecdysone synthesis in the PG of lepidopterans (Beydon & Lafont, 1983; Gilbert et al., 2002; Sakurai & Williams, 1989).”
BackgroundResult
Mechanisms regulating nutrition-dependent developmental plasticity through organ-specific effects in insects
Koyama, T., Mendes, C. C., & Mirth, C. K. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00263 · Cited by 144
“Ecdysone is produced by the prothoracic glands (PGs) via a series of cytochrome P450 enzymes, the so-called Halloween genes, from a cholesterol precursor (Gilbert et al., 2002).”
Background
Daphnia Halloween genes that encode cytochrome P450s mediating the synthesis of the arthropod molting hormone: Evolutionary implications
Rewitz, K., & Gilbert, L. I. (2008) · BMC Evolutionary Biology · doi:10.1186/1471-2148-8-60 · Cited by 139
“However, it must be emphasized that the Black Box may hold more than one reaction and more than one enzyme may be participating in this conversion [5].”
Background
Ecdysteroid Chemistry and Biochemistry
Lafont, R., Dauphin‐Villemant, C., Warren, J. T., & Rees, H. (2005) · Elsevier eBooks · doi:10.1016/b0-44-451924-6/00035-1 · Cited by 137
Ecological significance of sterols in aquatic food webs
Martin‐Creuzburg, D., & von Elert, E. (2009) · Springer eBooks · doi:10.1007/978-0-387-89366-2_3 · Cited by 137
“In general, the prohormone ecdysone is synthesized from dietary sterols (i.e., specifically from cholesterol) and subsequently hydroxylated by target tissues to 20-hydroxyecdysone, the most active ecdysteroid in arthropods (Grieneisen 1994; Gilbert et al. 2002; Martin-Creuzburg et al. 2007; Fig.”
BackgroundInfluential
Post-transcriptional regulation of insect metamorphosis and oogenesis
Song, J., & Zhou, S. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03361-5 · Cited by 140
Nuclear Receptor DHR4 Controls the Timing of Steroid Hormone Pulses During Drosophila Development
Ou, Q., Magico, A., & King‐Jones, K. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001160 · Cited by 135
“This succession of uncharacterized reactions is generally referred to as the ‘‘Black Box’’ and is believed to harbor the rate-limiting step for the production of ecdysone [25].”
Prothoracicotropic Hormone
Rybczynski, R. (2005) · Elsevier eBooks · doi:10.1016/b0-44-451924-6/00033-8 · Cited by 133
A Molecular Genetic Approach to the Biosynthesis of the Insect Steroid Molting Hormone
Gilbert, L. I., & Warren, J. T. (2005) · Vitamins and hormones · doi:10.1016/s0083-6729(05)73002-8 · Cited by 134
Gonadal Ecdysteroidogenesis in Arthropoda: Occurrence and Regulation
Brown, M. R., Sieglaff, D. H., & Rees, H. H. (2008) · Annual Review of Entomology · doi:10.1146/annurev.ento.53.103106.093334 · Cited by 129
Transcriptional regulation of insect steroid hormone biosynthesis and its role in controlling timing of molting and metamorphosis
Niwa, Y. S., & Niwa, R. (2015) · Development Growth & Differentiation · doi:10.1111/dgd.12248 · Cited by 128
“While PTTH has been extensively studied for its short-term prothoracicotropic activity, which requires the de novo translation of proteins (Gilbert et al. 2002), PTTH also influences transcription in the PG, which might have a long-term effect on ecdysteroid biosynthesis (Ou & King-Jones 2013).”
Background
Bombyx prothoracicostatic peptides activate the sex peptide receptor to regulate ecdysteroid biosynthesis
Yamanaka, N., Hua, Y., Roller, L., Spalovská, I., Mizoguchi, A., Kataoka, H., & Tanaka, Y. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907471107 · Cited by 126
“E are steroidhormones that play a crucial role in insect development and metamorphosis as molting hormones (1, 2).”
Background
Steroid Hormone Inactivation Is Required during the Juvenile-Adult Transition in Drosophila
Rewitz, K., Yamanaka, N., & O’Connor, M. B. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.10.021 · Cited by 124
“Although the mechanisms that control the rise in 20E are well studied (Caldwell et al., 2005; Colombani et al., 2005; Gilbert et al., 2002; Layalle et al., 2008; McBrayer et al., 2007; Rewitz et al., 2009a, 2009b), the physiological significance of 20E inactivation is largely unexplored except for…”
Background
The ecdysteroidogenic P450 Cyp302a1/disembodied from the silkworm, Bombyx mori , is transcriptionally regulated by prothoracicotropic hormone
Niwa, R., Sakudoh, T., Namiki, T., Saida, K., Fujimoto, Y., & Kataoka, H. (2005) · Insect Molecular Biology · doi:10.1111/j.1365-2583.2005.00587.x · Cited by 120
“It is known that treatment with PTTH stimulates gene transcription in the PG (Keightley et al., 1990), but the identities of the genes thus regulated have not been elucidated (Gilbert et al., 2002).”
BackgroundInfluential
The Phytochemical, Biological, and Medicinal Attributes of Phytoecdysteroids: An Updated Review
Das, N., Mishra, S. K., Bishayee, A., Ali, E. S., & Bishayee, A. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.10.012 · Cited by 115
“(23)(48), achyranthesterone A [2b,3b,14a,20S,21,22R,25-heptahydroxycholest-7-en-6-one] (24)(49), (20R,22R)-2b,3b,20,22,26-pentahydroxy-cholestan-7,12-dien-6-one (25)(50), isolated from the plant Achyranthes bidentata(50), aervecdysteroid A [20,25-epoxy-2b,3b, 14a,22b-tetrahydroxy-5b-ecdysteroid] (26), aervecdysteroid…”
Background
Life-History Evolution and the Polyphenic Regulation of Somatic Maintenance and Survival
Flatt, T., Amdam, G. V., Kirkwood, T. B. L., & Omholt, S. W. (2013) · The Quarterly Review of Biology · doi:10.1086/671484 · Cited by 114
Developmental characterization, function and regulation of a Laccase2 encoding gene in the honey bee, Apis mellifera (Hymenoptera, Apinae)
Elias-Neto, M., Soares, M. P. M., Simões, Z. L. P., Hartfelder, K., & Bitondi, M. M. G. (2010) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2010.02.004 · Cited by 113
Structural and Functional Evolution of the Translocator Protein (18 kDa)
Fan, J., Lindemann, P., Feuilloley, M. G. J., & Papadopoulos, V. (2012) · Current Molecular Medicine · doi:10.2174/1566524011207040369 · Cited by 118
“The early steps in the regulation of ecdysteroid synthesis remain unknown, but are likely to occur in the mitochondria and have been characterized as the rate-limiting “black box” in ecdysteroid biosynthesis [109].”
Background
Dynamic regulation of Drosophila nuclear receptor activity in vivo
Musselman, L. P., Necakov, A., Sampson, H. M., Ni, R., Hu, C., Thummel, C. S., & Krause, H. M. (2006) · Development · doi:10.1242/dev.02512 · Cited by 110
“…whether this activity pattern reflects the presence of ligand, we tested the dependence of this localized GAL4-EcR transcriptional activity on the biosynthesis of -ecdysone (E), which is the immediate precursor of 20-hydroxyecdysone (20E), the active ecdysteroid in insects (Gilbert et al., 2002).”
Background
Early transcriptional events linked to induction of diapause revealed by RNAseq in larvae of drosophilid fly, Chymomyza costata
Poupardin, R., Schöttner, K., Korbelová, J., Provazník, J., Doležel, D., Pavlinić, D., Beneš, V., & Košťál, V. (2015) · BMC Genomics · doi:10.1186/s12864-015-1907-4 · Cited by 107
“Ecdysone is released by ring gland and further converted into the active hormone 20-hydroxyecdysone (20-HE) in target tissues [71, 73].”
Background
Identification, characterization and developmental expression of Halloween genes encoding P450 enzymes mediating ecdysone biosynthesis in the tobacco hornworm, Manduca sexta
Rewitz, K., Rybczynski, R., Warren, J. T., & Gilbert, L. I. (2006) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2005.12.002 · Cited by 106
Insecticides induce the co-expression of glutathione S-transferases through ROS/CncC pathway in Spodoptera exigua
Hu, B. H., Hu, S., Huang, H., Wei, Q., Ren, M., Huang, S., Tian, X., & Su, J. (2019) · Pesticide Biochemistry and Physiology · doi:10.1016/j.pestbp.2019.01.008 · Cited by 107
A Halloween gene noppera-bo encodes a glutathione S-transferase essential for ecdysteroid biosynthesis via regulating the behaviour of cholesterol in Drosophila
Enya, S., Ameku, T., Igarashi, F., Iga, M., Kataoka, H., Shinoda, T., & Niwa, R. (2014) · Scientific Reports · doi:10.1038/srep06586 · Cited by 106
Intercellular signaling of reproductive development by theC. elegansDAF-9 cytochrome P450
Mak, H. Y., & Ruvkun, G. (2004) · Development · doi:10.1242/dev.01069 · Cited by 103
“This is similar to cases in Drosophila and mammals, where hormone availability is modulated locally by enzymes, such as cytochrome P450, in target tissues (Luu-The, 2001; Gilbert et al., 2002).”
Method
Ecdysone steroid hormone remote controls intestinal stem cell fate decisions via the PPARγ-homolog Eip75B in Drosophila
Zipper, L., Jassmann, D., Burgmer, S., Görlich, B., & Reiff, T. (2020) · eLife · doi:10.7554/elife.55795 · Cited by 98
Halloween genes and nuclear receptors in ecdysteroid biosynthesis and signalling in the pea aphid
Christiaens, O., Iga, M., Velarde, R. A., Rougé, P., & Smagghe, G. J. (2010) · Insect Molecular Biology · doi:10.1111/j.1365-2583.2009.00957.x · Cited by 96
“The whole trafficking mechanism of the ecdysteroid precursors has not been elucidated yet in insects, but it may use similar mechanisms as the steroidogenesis in vertebrates (Rees, 1995; Gilbert et al., 2002; Lafont et al., 2005; Huang et al., 2008).”
Background
Identification of a Novel Prothoracicostatic Hormone and Its Receptor in the Silkworm Bombyx mori
Yamanaka, N., Hua, Y., Mizoguchi, A., Watanabe, K., Niwa, R., Tanaka, Y., & Kataoka, H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500308200 · Cited by 96
Ecdysone agonists: Mechanism and importance in controlling insect pests of agriculture and forestry
Retnakaran, A., Krell, P. J., Feng, Q., & Arif, B. M. (2003) · Archives of Insect Biochemistry and Physiology · doi:10.1002/arch.10116 · Cited by 93
FXPRL-amide peptides induce ecdysteroidogenesis through a G-protein coupled receptor expressed in the prothoracic gland of Bombyx mori
Watanabe, K., Hull, J. J., Niimi, T., Imai, K., Matsumoto, S., Yaginuma, T., & Kataoka, H. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.05.008 · Cited by 89
NCR-1 and NCR-2, the C. elegans homologs of the human Niemann-Pick type C1 disease protein, function upstream of DAF-9 in the dauer formation pathways
Li, J., Brown, G., Ailion, M., Lee, S., & Thomas, J. H. (2004) · Development · doi:10.1242/dev.01408 · Cited by 89
“Although the pathway for ecdysone biosynthesis has not been fully characterized, cytochrome P450 enzymes are likely to catalyze many of the hydroxylation steps (Gilbert et al., 2002).”
Background
Regulation of insect steroid hormone biosynthesis by innervating peptidergic neurons
Yamanaka, N., Žitňan, D., Kim, Y., Adams, M. E., Hua, Y., Suzuki, Y., Suzuki, M., Suzuki, A., Satake, H., Mizoguchi, A., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511196103 · Cited by 89
Expression of genes encoding proteins involved in ecdysteroidogenesis in the female mosquito, Aedes aegypti
Sieglaff, D. H., Duncan, K. A., & Brown, M. R. (2005) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2005.01.011 · Cited by 88
“The next step is believed to be the rate limiting step of ecdysteroidogenesis, and it involves the transport of 7-dehydrocholesterol to the inner mitochondrial matrix for further processing (Warren and Gilbert, 1996; Henrich et al., 1999; Gilbert et al., 2002).”
BackgroundInfluential
Structure of the heterodimeric ecdysone receptor DNA‐binding complex
Devarakonda, S., Harp, J. M., Kim, Y., Ożyhar, A., & Rastinejad, F. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg569 · Cited by 87
Insulin stimulates ecdysteroidogenesis by prothoracic glands in the silkworm, Bombyx mori
Gu, S., Lin, J., Lin, P., & Chen, C.-H. (2008) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2008.10.012 · Cited by 86
What Goes Up Must Come Down
Ou, Q., & King‐Jones, K. (2013) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-385979-2.00002-2 · Cited by 86
Role of the Halloween genes, Spook and Phantom in ecdysteroidogenesis in the desert locust, Schistocerca gregaria
Marchal, E., Badisco, L., Verlinden, H., Vandersmissen, T., Soest, S. V., Wielendaele, P. V., & Broeck, J. V. (2011) · Journal of Insect Physiology · doi:10.1016/j.jinsphys.2011.05.009 · Cited by 85
“Carnivorous insects can take it directly from their prey, whereas in phytophagous insects, phytosterols are first dealkylated to cholesterol (Gilbert et al., 2002; Gilbert and Warren, 2005).”
Background
Bracoviruses Contain a Large Multigene Family Coding for Protein Tyrosine Phosphatases
Provost, B., Varricchio, P., Arana, E. I., Espagne, E., Falabella, P., Huguet, E., Scaleia, R. L., Cattolico, L., Poirié, M., Malva, C., et al. (2004) · Journal of Virology · doi:10.1128/jvi.78.23.13090-13103.2004 · Cited by 85
Molecular characterization and expression of prothoracicotropic hormone during development and pupal diapause in the cotton bollworm, Helicoverpa armigera
Wei, Z., Zhang, Q., Kang, L., Xu, W., & Denlinger, D. L. (2005) · Journal of Insect Physiology · doi:10.1016/j.jinsphys.2005.03.005 · Cited by 84
“diapause (Denlinger, 1985; Ishizaki and Suzuki, 1994; Gilbert et al., 2002).”
Background
Ecdysteroids Regulate the Levels of Molt-Inhibiting Hormone (MIH) Expression in the Blue Crab, Callinectes sapidus
Techa, S., & Chung, J. S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117278 · Cited by 83
“sexta and Pieris brassicae [1,6–8].”
Critical Role of Desolvation in the Binding of 20-Hydroxyecdysone to the Ecdysone Receptor
Browning, C., Martin, E., Loch, C., Wurtz, J., Moras, D., Stote, R. H., Dejaegere, A. P., & Billas, I. M. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705559200 · Cited by 86
Prothoracicotropic Hormone
Smith, W. A., & Rybczynski, R. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-384749-2.10001-9 · Cited by 86
Regulation of ecdysone production in Drosophila by neuropeptides and peptide hormones
Kannangara, J. R., Mirth, C. K., & Warr, C. G. (2021) · Open Biology · doi:10.1098/rsob.200373 · Cited by 84
“It is then converted to its active form, 20E, by Shade and can bind to the nuclear receptor complex, Ecdysone Receptor (EcR) and Ultraspiracle (Usp), to activate the downstream transcription factors that promote developmental transitions [36].”
Background
Identification and expression profile of Halloween genes involved in ecdysteroid biosynthesis in Spodoptera littoralis
Iga, M., & Smagghe, G. J. (2009) · Peptides · doi:10.1016/j.peptides.2009.08.002 · Cited by 82
“Insects may have similar trafficking mechanisms to vertebrate steroidogenesis and shuttle between the endoplasmic reticulum (ER) and mitochondria for modification, but the details are unclear [11,17,20,31].”
Background
Rhodnius, Golden Oil, and Met: A History of Juvenile Hormone Research
Riddiford, L. M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00679 · Cited by 84
The Fruit FlyDrosophila melanogasteras a Model System to Study Cholesterol Metabolism and Homeostasis
Niwa, R., & Niwa, Y. S. (2011) · Cholesterol · doi:10.1155/2011/176802 · Cited by 82
“Ecdysteroid biosynthesis occurs in a specialized endocrine organ called the prothoracic gland (PG) during the larval stages or in ovaries of adult females.”
BackgroundMethod
Differential expression of the detoxification genes in the different life stages of the malaria vector Anopheles gambiae
Strode, C., Steen, K., Ortelli, F., & Ranson, H. (2006) · Insect Molecular Biology · doi:10.1111/j.1365-2583.2006.00667.x · Cited by 85
“…and adult ovary development and consists of CYP302A1 ( disembodied ), CYP306A1 ( phantomn ), CYP307A1 ( spook ), CYP315A1 ( shadow ) and CYP314A1 ( shade ) (Chavez et al ., 2000; Gilbert et al ., 2002; Warren et al ., 2002, 2004; Petryk et al ., 2003; Namiki et al ., 2005; Niwa et al ., 2005).”
Background
20-Hydroxyecdysone (20E) Primary Response Gene E75 Isoforms Mediate Steroidogenesis Autoregulation and Regulate Developmental Timing in Bombyx
Li, K., Tian, L., Guo, Z., Guo, S., Zhang, J., Gu, S., Palli, S. R., Cao, Y., & Li, S. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.737072 · Cited by 81
“The prothoracic glands produce and secrete ecdysone; once released into the hemolymph, ecdysone is converted to 20E in the peripheral tissues, such as the fat body and midgut (34).”
Background

Authors: Gilbert, L. I., Rybczynski, R., & Warren, J. T.
Affiliations: University of North Carolina at Chapel Hill (US)
Venue: Annual Review of Entomology
Publisher: Annual Reviews
Published: 2002-01
Volume: 47
Issue: 1
Pages: 883-916
ISSN: 0066-4170 (ISSN-L)
1545-4487
DOI: 10.1146/annurev.ento.47.091201.145302
OpenAlex: W2157228103
Cited by: 532
References: 185
Citations by year: 2026: 15 · 2025: 20 · 2024: 16 · 2023: 14 · 2022: 14 · 2021: 21 · 2020: 32 · 2019: 20 · 2018: 11 · 2017: 13 · 2016: 20 · 2015: 21 · 2014: 31 · 2013: 28 · 2012: 26
FWCI: 2.40
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Entomology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords: ecdysteroid biosynthesis, 20-hydroxyecdysone, ecdysone, prothoracic gland, prothoracicotropic hormone, molting, metamorphosis, cholesterol conversion, steroidogenesis, insect endocrinology
MeSH terms: Animals, Insecta, Down-Regulation, Ecdysteroids

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Control and Biochemical Nature of the Ecdysteroidogenic Pathway

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks