Local action of thyroxine analogues on amphibian metamorphosis

Abstract

To determine whether or not thyroxine analogues can accelerate metamorphosis by acting directly upon peripheral tissues, thyroxine analogue-cholesterol pellets were implanted into the dorsal tail fins of Rana pipiens larvae. Many analogues tested brought about localized fin resorption in the region in which they were implanted; this was attributed to the direct action of the analogue upon the fin. Triiodothyronine and two of the acrylic acid analogues tested were more active than thyroxine. On the other hand, metamorphosing activity was reduced in compounds with bromine atom replacements for iodine atoms, with only two halogen atoms instead of four, with a methoxy group as a substitution for the hydroxyl group, and with a carboxyl or an amino group as replacement for the alanine side chain. No activity was detected for single ring compounds unlikely to condense, thyronine, and meta- and ortho- thyroxine. Although intra-fin implants of single ring compounds likely to condense to diphenyl ethers did not induce local fin resorption in the concentrations tested, large intraperitoneal implants stimulated general metamorphic progress, as evidenced by accelerated hind limb development and a decrease in length of the tadpoles. Moreover, fairly high concentrations of diiodohydroxy-benzoic and phenylacetic acids implanted either subcutaneously near the operculum or intraorbitally induced opercular thinning and perforation or incipient upper eyelid development (two metamorphic events with lower thresholds of response to thyroxine than tail fin resorption). Any condensation of these compounds to their corresponding diphenyl ethers must have occurred in the target organs. The experiments demonstrate the direct, local action of certain thyroxine analogues upon peripheral tissues of the tadpole.