What goes up must come down: transcription factors have their say in making ecdysone pulses

Insect metamorphosis is one of the most fascinating biological processes in the animal kingdom. The dramatic transition from an immature juvenile to a reproductive adult is under the control of the steroid hormone ecdysone, also known as the insect molting hormone. During Drosophila development, periodic pulses of ecdysone are released from the prothoracic glands, upon which the hormone is rapidly converted in peripheral tissues to its biologically active form, 20-hydroxyecdysone. Each hormone pulse has a unique profile and causes different developmental events, but we only have a rudimentary understanding of how the timing, amplitude, and duration of a given pulse are controlled. A key component involved in the timing of ecdysone pulses is PTTH, a brain-derived neuropeptide. PTTH stimulates ecdysone production through a Ras/Raf/ERK signaling cascade; however, comparatively little is known about the downstream targets of this pathway. In recent years, it has become apparent that transcriptional regulation plays a critical role in regulating the synthesis of ecdysone, but only one transcription factor has a well-defined link to PTTH. Interestingly, many of the ecdysteroidogenic transcription factors were originally characterized as primary response genes in the ecdysone signaling cascade that elicits the biological responses to the hormone in target tissues. To review these developments, we will first provide an overview of the transcription factors that act in the Drosophila ecdysone regulatory hierarchy. We will then discuss the roles of these transcriptional regulators in controlling ecdysone synthesis. In the last section, we will briefly outline transcription factors that likely have roles in regulating ecdysone synthesis but have not been formally identified as downstream effectors of ecdysone.