Acceleration of Anuran Amphibian Metamorphosis by Corticotropin-Releasing Hormone-like Peptides

Despite substantial information on the role of the pituitary-thyroid and pituitary-interrenal axes in controlling amphibian metamorphosis, the hypothalamic hormones responsible for controlling the activity of these axes have not been identified. The mammalian thyrotropin-releasing hormone (TRH) does not regulate the thyroid axis of tadpoles; however, corticotropin releasing hormone (CRH) stimulates the release of thyrotropin from bullfrog tadpole pituitary glands in vitro and may thus function as a central regulator of the thyroid axis during metamorphosis. I tested the possibility that a CRH-like peptide is involved in controlling amphibian development by treating tadpoles of two anuran species, the western spadefoot toad Scaphiopus hammondii , and the North American bullfrog, Rana catesbeiana, with neuropeptides and monitoring their effects on metamorphosis. Injection of spadefoot toad tadpoles with ovine (o) CRH (2 μg/animal every other day for 3 weeks) or the amphibian CRH-like peptide sauvagine (SV) significantly decreased their time from hatching to metamorphic climax (Gosner stage 42; frontlimb emergence) and their body weight and body length at climax compared with vehicle-injected controls: whereas, TRH had no effect and arginine vasotocin produced a small but significant lengthening of the larval period but did not alter body size at climax. In an acute response experiment, S. hammondii tadpoles (in Gosner stages 36-38—late prometamorphosis) treated with oCRH or SV (2 μg/animal) exhibited significantly elevated whole-body thyroxine (T 4) content at 2 and 6 hr after injection; whereas, treatment with TRH (2 μg/animal) did not significantly alter whole-body T 4. R. catesbeiana tadpoles treated with oCRH or SV (surgical implantation of ELVAX pellets impregnated with 100 μg peptide and injections of peptides at 5 μg/animal once every 3 days) exhibited accelerated spontaneous and triiodothyronine (T 3)induced metamorphosis as assessed by changes in tail height, hind limb development, and body weight; TRH had no effect. Injections of a pool of antisera generated against CRH-like peptides (rat/human CRH. oCRH, SV) slowed T 3-induced metamorphosis when compared with normal serum-injected controls. These results support the hypothesis that a CRH-like peptide(s) is involved in the central control of metamorphosis of anuran amphibians, and may act, at least in part, through stimulation of the thyroid axis.