Initiation of metamorphosis and control of ecdysteroid biosynthesis in insects: The interplay of absence of Juvenile hormone, PTTH, and Ca(2+)-homeostasis.

The paradigm saying that release of the brain neuropeptide big prothoracicotropic hormone (PTTH) initiates metamorphosis by activating the Torso-receptor/ERK pathway in larval prothoracic glands (PGs) is widely accepted nowadays. Upon ligand-receptor interaction Ca(2+) enters the PG cells and acts as a secondary messenger. Ecdysteroidogenesis results, later followed by apoptosis. Yet, some data do not fit in this model. In some species decapitated animals can still molt, even repeatedly, and metamorphose. PTTH does not universally occur in all insect species. PGs may also have other functions; PGs as counterpart of the vertebrate thymus? There are also small PTTHs. Finally, PTTH remains abundantly present in adults and plays a role in control of ecdysteroidogenesis (=sex steroid production) in gonads. This is currently documented only in males. This urges a rethinking of the PTTH-PG paradigm. The key question is: Why does PTTH-induced Ca(2+) entry only result in ecdysteroidogenesis and apoptosis in specific cells/tissues, namely the PGs and gonads? Indeed, numerous other neuropeptides also use Ca(2+) as secondary messenger. The recent rediscovery that in both invertebrates and vertebrates at least some isoforms of Ca(2+)-ATPase need the presence of an endogenous farnesol/juvenile hormone(JH)-like sesquiterpenoid for keeping cytosolic [Ca(2+)]i below the limit of apoptosis-induction, triggered the idea that it is not primarily PTTH, but rather the drop to zero of the JH titer that acts as the primordial initiator of metamorphosis by increasing [Ca(2+)]i. PTTH likely potentiates this effect but only in cells expressing Torso. PTTH: an evolutionarily ancient gonadotropin?