Anterior pituitary and adrenal cortical hormones accelerate or inhibit tadpole hindlimb growth and development depending on stage of spontaneous development or thyroxine concentration in induced metamorphosis.

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.