Department of Science, Roskilde University, Denmark.
Dev Cell. 2010 Dec 14;19(6):895-902. doi: 10.1016/j.devcel.2010.10.021.
Steroid hormones are systemic signaling molecules that regulate juvenile-adult transitions in both insects and mammals. In insects, pulses of the steroid hormone 20-hydroxyecdysone (20E) are generated by increased biosynthesis followed by inactivation/clearance. Although mechanisms that control 20E synthesis have received considerable recent attention, the physiological significance of 20E inactivation remains largely unknown. We show that the cytochrome P450 Cyp18a1 lowers 20E titer during the Drosophila prepupal to pupal transition. Furthermore, this reduction of 20E levels is a prerequisite to induce βFTZ-F1, a key factor in the genetic hierarchy that controls early metamorphosis. Resupplying βFTZ-F1 rescues Cyp18a1-deficient prepupae. Because Cyp18a1 is 20E-inducible, it appears that the increased production of steroid is responsible for its eventual decline, thereby generating the regulatory pulse required for proper temporal progression of metamorphosis. The coupling of hormone clearance to βFTZ-F1 expression suggests a general mechanism by which transient signaling drives unidirectional progression through a multistep process.
甾体激素是系统信号分子，可调节昆虫和哺乳动物的幼体-成体过渡。在昆虫中，类固醇激素 20-羟蜕皮酮（20E）的脉冲是通过增加生物合成，然后失活/清除来产生的。尽管控制 20E 合成的机制最近受到了相当多的关注，但 20E 失活的生理意义在很大程度上仍然未知。我们表明，细胞色素 P450 Cyp18a1 在果蝇预蛹到蛹化过渡期间降低 20E 的效价。此外，这种 20E 水平的降低是诱导βFTZ-F1 的前提，βFTZ-F1 是控制早期变态的遗传层次中的关键因素。βFTZ-F1 的补充挽救了 Cyp18a1 缺陷的预蛹。由于 Cyp18a1 是 20E 诱导的，因此似乎增加的类固醇产生是其最终下降的原因，从而产生了适当的变态时间进展所需的调节脉冲。激素清除与βFTZ-F1 表达的偶联表明了一种普遍的机制，即瞬时信号驱动通过多步过程的单向进展。
