In C. elegans larvae, steroid hormone signalling functions with insulin/IGF-1-like signalling to promote reproductive development and to prevent dauer arrest - in hostile conditions, larvae enter the dormant diapausal dauer stage instead of becoming adults. Now, Patel and colleagues have discovered a key enzyme in the biosynthetic pathway used by C. elegans to make steroid hormones - HSD-1, which is orthologous to vertebrate 3β-hydroxysteroid dehydrogenases (3β-HSDs; see p. 2239). They found HSD-1 by screening for mutations that enhance the dauer phenotype of ncr-1 mutants; NCR-1 and NCR-2 are intracellular cholesterol transporters that prevent dauer arrest. hsd-1; ncr-1 double mutants, they report, fail to inhibit dauer arrest; feeding these worms with certain steroid hormone precursors rescues this defect. They also show that reduction of the HSD-1-mediated steroid signal alters the subcellular localization of the DAF-16/FOXO transcription factor, a component of the insulin signalling pathway. This important result reveals a novel way in which steroid hormone and insulin/IGF-1-like signalling can intersect to direct development.
Worming into steroid and insulin signal intersection
Worming into steroid and insulin signal intersection. Development 1 July 2008; 135 (13): e1301. doi:
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