The effect of prolactin, growth hormone, and various adrenal corticoids on hindlimb growth, development, and differentiation was studied in Rana pipiens larvae. Experiments were performed at different stages of spontaneous development and during metamorphosis induced in premetamorphic tadpoles by various concentrations of exogenous T4. Prolactin at 10 micrograms/day inhibited the limb at spontaneous premetamorphosis, had no effect at prometamorphosis or when administered with 3.8 nM T4, and synergized with T4 at 63 nM T4 and above. Growth hormone (10 or 20 micrograms/day) promoted limb growth and development during premetamorphosis but had no effect on spontaneous or induced metamorphosis thereafter, nor did it stimulate limb epidermal differentiation. The adrenal corticoids inhibited limb growth and epidermal cell proliferation during pre- and prometamorphosis but had no effect on limb morphogenesis or differentiation. The depressive effect of corticoids during spontaneous metamorphosis is at least partly through thyroid inhibition since hydrocortisone significantly reduced follicle cell height, lumen diameter, and cell proliferation in the thyroid. During induced metamorphosis, steroids (0.29 microM), especially corticosterone and aldosterone, antagonized the effect of 0.38 to 1.2 nM T4 on the limb. All steroids except deoxycorticosterone synergized with 3.8 nM T4, and at 31 nM T4, approximating the climax level with permeability factors taken into account, all corticoids synergized with T4 to promote limb growth and development. Aldosterone antagonized T4 at a higher T4 level than the other corticoids. The effect of all steroids except corticosterone was also corticoid dose-dependent. The results show the importance of the T4 concentrations in interactions of T4 with other hormones and suggest a scheme for hormonal control of limb growth and morphogenesis during metamorphosis. During premetamorphosis growth hormone synergizes with low endogenous T4 to promote initial limb growth and development while prolactin opposes this action. During prometamorphosis, as growth hormone and prolactin become ineffective corticosteroids begin to synergize with the rising level of endogenous T4. At climax, prolactin also augments the action of T4 to bring about rapid hindlimb growth.

No abstract

Metamorphosis of Rana pipiens tadpoles may be retarded when the light phase of the light/dark (LD) cycle is shortened or when thyroxine (T4) is given in the dark because melatonin peaks during the dark. Injection of premetamorphic tadpoles in spontaneous metamorphosis with melatonin (1 5 pg) retarded tail growth and hindlimb development on 18L:6D but had no significant effect on 6L: 18D. During induced metamorphosis (30 pg/liter T4), melatonin injections retarded tail resorption on 18L : 6D and accelerated it on 6L : 18D, but did not affect the hindlimb. When melatonin was injected during T4 immersion at different times in the photophase on 18L : 6D (L onset 0800 hr), tail regression was retarded by melatonin at 1430 or 2030 hr. At 0830 hr, shrinkage of tail length was accelerated whereas tail height was not affected. Tail tips in vifro induced to resorb by 0.2 pg/ml T4 in Niu-Twitty solution regressed more slowly in the presence of melatonin (10 or 15pg/ml) than with T4 alone on both 6L: 18D and 18L:6D. The findings implicate melatonin in LD cycle effects on tadpole metamorphic rate in vivo, show the importance of the time of melatonin injections, and indicate that melatonin antagonizes the metamorphic action of T4 at the tissue level.