Control and Biochemical Nature of the Ecdysteroidogenic Pathway

Abstract

Molting is elicited by a critical titer of ecdysteroids that includes the principal molting hormone, 20-hydroxyecdysone (20E), and ecdysone (E), which is the precursor of 20E but also has morphogenetic roles of its own. The prothoracic glands are the predominate source of ecdysteroids, and the rate of synthesis of these polyhydroxylated sterols is critical for molting and metamorphosis. This review concerns three aspects of ecdysteroidogenesis: (a) how the brain neuropeptide prothoracicotropic hormone (PTTH) initiates a transductory cascade in cells of the prothoracic gland, which results in an increased rate of ecdysteroid biosynthesis (upregulation); (b) how the concentrations of 20E in the hemolymph feed back on the prothoracic gland to decrease rates of ecdysteroidogenesis (downregulation); and (c) how the prothoracic gland cells convert cholesterol to the precursor of E and then 20E, a series of reactions only now being understood because of the use of a combination of classical biochemistry and molecular genetics.

Nitric oxide directly regulates gene expression during Drosophila development: need some gas to drive into metamorphosis?: Figure 1.

“…Ecdysone biosynthesis (ecdysteroidogenesis) in the PG is mediated by multiple enzymes, each of which is engaged in a specific step of sequential hydroxylation and oxidation reactions (Gilbert et al 2002). Ecdysone, after being converted into active 20E in peripheral tissues, triggers gene expression cascades throughout the body leading to developmental transitions; i.e., molting and metamorphosis.…”

“…In Malpighian (renal) tubules of Drosophila, two neuropeptides, capa-1 and capa-2, increase fluid secretion rates through the up-regulation of intracellular Ca 2+ concentration and subsequent NOS/cyclic GMP signaling (Kean et al 2002). Since Ca 2+ signaling is known to have an important role in the fly PG (Venkatesh and Hasan 1997) and some neuropeptides like the prothoracicotropic hormone (PTTH) are known to activate the Ca 2+ signaling pathway in the PG to regulate ecdysteroidogenesis (Gilbert et al 2002), it will be interesting to see whether the activities of these ecdysteroidogenic neuropeptides are mediated by NOS.…”

Interaction of proteins involved in ecdysone and juvenile hormone signal transduction

“…Neurosecretory cells in the brain produce the prothoracicotrophic hormone (PTTH), which activates the prothoracic glands to produce ecdysone. Ecdysone is a prohormone; it is converted to the active hormone 20E in target tissues (Gilbert et al, 2002). Ecdysteroids activate the target genes through a heterodimeric receptor complex comprising the ecdysone receptor (EcR) (Koelle et al, 1991) and ultraspiracle (USP) (Henrich et al, 1990;Oro et al, 1990;Shea et al, 1990) proteins; both of them are members of the nuclear steroid/thyroid/retinoid receptor superfamily.…”

CYP306A1, a Cytochrome P450 Enzyme, Is Essential for Ecdysteroid Biosynthesis in the Prothoracic Glands of Bombyx and Drosophila

“…In the ecdysozoa (1) including insects, developmental schedules are mediated by molting, metamorphosis, and diapause. It is well known that steroid hormones play pivotal roles in such developmental timing in ecdysozoan organisms (2)(3)(4). In insects, molting and metamorphosis are elicited by critical titers of ecdysone and 20-hydroxyecdysone.…”