Steroidogenesis in zebrafish and mouse models

Hsu, Hwei-Jan; Hsu, Nai Chi; Hu, Meng Chun; Chung, Bon Chu

doi:10.1016/j.mce.2005.10.011

Cited by 39 publications

(28 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Following the production of P5 from cholesterol, P5 becomes the steroidogenic precursor for glucocorticoids ( 76 ), which play a central role in vertebrate development (77)(78)(79). Zebrafi sh embryos express a glucocorticoid receptor at early stages and readily process a synthetic glucocorticoid, Dex, when delivered in the embryo water ( 79,80 ).…”

Section: Disruption Of Npc1 Function Results In Actin Cytoskeleton DImentioning

confidence: 99%

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish

Schwend

Loucks

Snyder

et al. 2011

Journal of Lipid Research

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org ( 1,2 ). NP-C symptoms typically appear in childhood, although infant onsets are possible. By the time the disorder's symptoms manifest, signifi cant cellular damage has already occurred. At the cellular level, NP-C is characterized by an aberrant accumulation of unesterifi ed cholesterol and glycolipids in the late endosomes and lysosomes of the endocytotic pathway ( 3-6 ). The disease is caused by mutations in one of two genes, Niemann-Pick disease, type C1 ( NPC1 ), which accounts for 95% of cases, or NiemannPick disease, type C2 ( NPC2 ), which accounts for 4% of cases. The remaining 1% of cases involves patients with confi rmed biochemical defects without an accompanying identifi ed mutation ( 7-10 ).The function of NPC1 involves regulating the movement of LDL-derived cholesterol and plasma-derived glycolipids from the endocytotic pathway to the endoplasmic reticulum/trans-Golgi network (ER/TGN) and the mitochondrial membrane ( 11-15 ). Despite reductions in sterol exit from the endocytotic pathway, NPC1-defi cient cells display normal sterol uptake, proper sterol delivery to the endocytotic organelles, and unperturbed levels of cholesterol ester hydrolysis ( 3,16,17 ). Excessive sterol content in the liver and spleen likely accounts for reports of hepato-splenomegaly, whereas sterol accumulation in the brain may contribute to the neurological deterioration in NP-C patients ( 16,(18)(19)(20).Abstract Niemann-Pick disease, type C (NP-C), often associated with Niemann-Pick disease, type C1 (NPC1) mutations, is a cholesterol-storage disorder characterized by cellular lipid accumulation, neurodegeneration, and reduced steroid production. To study NPC1 function in vivo, we cloned zebrafi sh npc1 and analyzed its gene expression and activity by reducing Npc1 protein with morpholino (MO)-oligonucleotides. Filipin staining in npc1-morphant cells was punctate, suggesting abnormal accumulation of cholesterol. Developmentally, reducing Npc1 did not disrupt early cell fate or survival; however, early morphogenetic movements were delayed, and the actin cytoskeleton network was abnormal. MO-induced defects were rescued with ectopic expression of mouse NPC1 , demonstrating functional gene conservation, and by treatments with steroids pregnenolone or dexamethasone, suggesting that reduced steroidogenesis contributed to abnormal cell movements. Cell death was found in anterior tissues of npc1 morphants at later stages, consistent with fi ndings in mammals. Collectively, these studies show that npc1 is required early for proper cell movement and cholesterol localization and later for cell survival. -Schwend, T., E. J. Loucks, D. Snyder, and S. C. Ahlgren. Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafi sh. J.

show abstract

Section: Disruption Of Npc1 Function Results In Actin Cytoskeleton DImentioning

confidence: 99%

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish

Schwend

Loucks

Snyder

et al. 2011

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…Therefore, the conversion of cholesterol to 7dC is the first crucial step of steroid hormone bio- 81-29-853-6614; E-mail: ryusuke-niwa@umin.ac.jp. 5 The abbreviations used are: 7dC, 7-dehydrocholesterol; RP, reverse phase; ESI-MS/MS, electrospray ionization liquid chromatography-tandem mass spectrometry. …”

mentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

150

118

View full text Add to dashboard Cite

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...

show abstract

“…The interrenal tissue is the major site of steroidogenesis in most teleosts, as is the adrenal cortex in mammals. 14,35 In zebrafish, many steroidogenic genes have been cloned and identified, including side chain cleavage enzyme cyp11a1 (p540scc) 36,37 and steroidogenic acute regulatory protein (star), 38 both are known to mediate the rate-limiting steps of steroidogenesis. Cyp11a1 catalyzes the first step of adrenal steroidogenesis, while StAR regulates cholesterol shuttling across the mitochondrial membrane and the acute steroid production.…”

Section: Molecular Interplays Within Interrenal Primordiummentioning

confidence: 99%

Interrenal Organogenesis in the Zebrafish Model

Liu

2007

Organogenesis

View full text Add to dashboard Cite

In recent years, many genes that participate in the specification, differentiation and steroidogenesis of the interrenal organ, the teleostean homologue of the adrenal cortex, have been identified and characterized in zebrafish. In-depth studies of these genes have helped to delineate the morphogenetic steps of interrenal organ formation, as well as some of the molecular and cellular mechanisms that govern these processes. The codevelopment of interrenal tissue with the embryonic kidney (pronephros), surrounding endothelium and invading chromaffin cells has been analyzed, by virtue of the amenability of zebrafish embryos to a variety of genetic, developmental and histological approaches. Moreover, zebrafish embryos can be subject to molecular as well as biochemical assays for the unraveling of the transcriptional regulation program underlying interrenal development. To this end, the key mechanisms that control organogenesis and steroidogenesis of the zebrafish interrenal gland have been shown to resemble those in mammals, justifying the future utilization of zebrafish model for discovering novel genes associated with adrenal development and disease.

show abstract

Steroidogenesis in zebrafish and mouse models

Cited by 39 publications

References 12 publications

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish

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

Interrenal Organogenesis in the Zebrafish Model

Contact Info

Product

Resources

About