Attempts were made to induce metamorphosis in Mexican axolotls by treatment with TRH. Animals were injected with doses of 1-2 mg per 100g per day for 44-45 days, or immersed in water containing 1 mg of TRH per liter for 50 days. Results were uniformly negative despite the large doses administered. Treatment with TRH also had no significant effect on thyroid 131I metabolism. Rapid degradation of injected TRH by axolotl plasma was probably not a factor in the negative results since it was observed that axolotl plasma, unlike rat plasma, does not degrade TRH. Tadpole plasma similarly failed to degrade TRH, but frog plasma resembled rat plasma in its ability to degrade TRH very rapidly. TRH levels in the brain of axolotls and other amphibia were measured with the aid of a very sensitive radioimmunoassay. Highly significant endogenous levels were observed in both hypothalamus and extrahypothalamic brain tissue of axolotl, tiger salamander, and frog. The levels were higher than the corresponding values in rat brain. Evidence was obtained to support the conclusion that radioimmuno-assayable TRH in axolotl brain is identical with synthetic TRH. From these findings we conclude that (1) the axolotl is not deficient in TRH, (2) TRH deficiency is not a factor in the neoteny of axolotls, and (3) axolotl TRH is chemically indistinguishable from the synthetic tripeptide. Pituitaries from axolotls incubated in vitro with TRH did not show a stimulation of TSH release into the medium, although bioassayable TSH was readily detectable within the gland. This observation raised the possibility that the neoteny of the axolotl might be explained by insensitivity of its pituitary to stimulation by TRH. However, tiger salamander and frog pituitaries were also insensitive to authentic TRH, despite the fact that the frog pituitary contains a very high concentration of bioassayable TSH. Lack of responsiveness of the thyroid to TRH injections has also been reported in vivo for the tadpole, the chick, and the lungfish. The findings reported here raise the possibility that TRH in nonmammalian species serves some function other than that of stimulating TSH release from the pituitary.
ASJC Scopus subject areas
- Animal Science and Zoology