| Title: | "Genetic identification of HSD-1, a conserved steroidogenic enzyme that directs larval development in Caenorhabditis elegans" |
| Author(s): | Patel DS; Fang LL; Svy DK; Ruvkun G; Li W; |
| Address: | "Department of Biological Structure, University of Washington, Seattle, WA, USA" |
| ISSN/ISBN: | 0950-1991 (Print) 0950-1991 (Linking) |
| Abstract: | "In C. elegans, steroid hormones function in conjunction with insulin/IGF-1-like signaling in promoting reproductive development over entry into the diapausal dauer stage. The NCR-1 and -2 (NPC1-related) intracellular cholesterol transporters function redundantly in preventing dauer arrest, presumably by regulating the availability of substrates for steroid hormone synthesis. We have identified hsd-1 as a new component of this cholesterol trafficking/processing pathway, using an ncr-1 enhancer screen. HSD-1 is orthologous to 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerases (3beta-HSDs), which are key steroidogenic enzymes in vertebrates, and is exclusively expressed in two neuron-like XXX cells that are crucial in preventing dauer arrest, suggesting that it is involved in biosynthesis of dauer-preventing steroid hormones. The hsd-1 null mutant displays defects in inhibiting dauer arrest: it forms dauers in the deletion mutant backgrounds of ncr-1 or daf-28/insulin; as a single mutant, it is hypersensitive to dauer pheromone. We found that hsd-1 defects can be rescued by feeding mutant animals with several steroid intermediates that are either downstream of or in parallel to the 3beta-HSD function in the dafachronic acid biosynthetic pathway, suggesting that HSD-1 functions as a 3beta-HSD. Interestingly, sterols that rescued hsd-1 defects also bypassed the need for the NCR-1 and/or -2 functions, suggesting that HSD-1-mediated steroid hormone production is an important functional output of the NCR transporters. Finally, we found that the HSD-1-mediated signal activates insulin/IGF-I signaling in a cell non-autonomous fashion, suggesting a novel mechanism for how these two endocrine pathways intersect in directing development" |
| Keywords: | 3-Hydroxysteroid Dehydrogenases/genetics/*metabolism Animals Biological Transport Caenorhabditis elegans/*enzymology/genetics/*growth & development Caenorhabditis elegans Proteins/genetics/metabolism Endocrine System/metabolism *Gene Expression Regulation; |
| Notes: | "MedlinePatel, Dhaval S Fang, Lily L Svy, Danika K Ruvkun, Gary Li, Weiqing eng Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2008/05/23 Development. 2008 Jul; 135(13):2239-49. doi: 10.1242/dev.016972. Epub 2008 May 21" |
