AMPHIBIAN LIMB REGENERATION
241
way of the adrenal cortex. Finally, the problem as to which of the
hormones of the pituitary and of the adrenal cortex are involved in
regeneration is still to be clarified.
The influence of the thyroid secretion on regeneration has been extensively investigated, particularly in anurans where thyroid-induced
metamorphic effects are of dramatic proportions. Thyroxine administered
before amputation inhibits limb regeneration but accelerates regeneration
if given at blastemal phases (Speidel, 1929). In the urodele, where the
metamorphic changes are less drastic and possibly provide less of a
complication for regeneration, thyroxine effects are quite opposite to
those found in anurans. Thus, Hay (1956), in a comprehensive study,
found that thyroxine (1.10
- 6
) had no effect on limb regeneration of the
newt when administered prior to amputation, but was partially inhibitory
when given during blastemal growth phases. She suggests that thyroxine
depresses cellular proliferation. Removal of the thyroid (Schotte and
Washburn, 1954; Richardson, 1940, 1945) in the newt causes retarded
or abnormal regeneration so that a minimal level of thyroxine is necessary for limb regeneration to proceed, although the reason for this remains
unknown. Schmidt (1958a,b), however, finds that thyroidectomy performed 10 to 30 days prior to limb amputation results in a considerable
increase in the rate of regeneration. Wound epidermis gives every indication of being highly active and stump tissue dedifferentiation in these
newts is particularly rapid so that blastemal cells accumulate precociously. Accessory thyroid follicles were found in nearly one-third of
the newts so that Schmidt (1958b) prefers to consider his salamanders
as hypothyroid rather than athyroid.
Perhaps recent studies of Etkin and Gona (1967) may help in understanding the seeming inconsistencies of thyroid influences on newt limb
regeneration. They report that in frog tadpoles there is an antagonism
between thyroxine and prolactin; prolactin activity (on growth) is
greatest in premetamorphic stages but decreases to a minimum at
metamorphic climax. This behavior is the reciprocal of that for thyroxine.
To account for this they propose "that hypothalamic activity promotes
thyroid stimulating hormone secretion and inhibits prolactin secretion
by the tadpole's pituitary" (p. 257). The initiation of this hypothalamic
activity is thought to be by a positive feedback of thyroxine to the
hypothalamus. In Schmidt's experiments, could it be possible that the
prolonged hypothyroid state lifted the hypothalamic inhibition on the
secretion of prolactin which then could be released in large amounts to
stimulate limb regeneration? Thyroxine is most effective in restricting
241
way of the adrenal cortex. Finally, the problem as to which of the
hormones of the pituitary and of the adrenal cortex are involved in
regeneration is still to be clarified.
The influence of the thyroid secretion on regeneration has been extensively investigated, particularly in anurans where thyroid-induced
metamorphic effects are of dramatic proportions. Thyroxine administered
before amputation inhibits limb regeneration but accelerates regeneration
if given at blastemal phases (Speidel, 1929). In the urodele, where the
metamorphic changes are less drastic and possibly provide less of a
complication for regeneration, thyroxine effects are quite opposite to
those found in anurans. Thus, Hay (1956), in a comprehensive study,
found that thyroxine (1.10
- 6
) had no effect on limb regeneration of the
newt when administered prior to amputation, but was partially inhibitory
when given during blastemal growth phases. She suggests that thyroxine
depresses cellular proliferation. Removal of the thyroid (Schotte and
Washburn, 1954; Richardson, 1940, 1945) in the newt causes retarded
or abnormal regeneration so that a minimal level of thyroxine is necessary for limb regeneration to proceed, although the reason for this remains
unknown. Schmidt (1958a,b), however, finds that thyroidectomy performed 10 to 30 days prior to limb amputation results in a considerable
increase in the rate of regeneration. Wound epidermis gives every indication of being highly active and stump tissue dedifferentiation in these
newts is particularly rapid so that blastemal cells accumulate precociously. Accessory thyroid follicles were found in nearly one-third of
the newts so that Schmidt (1958b) prefers to consider his salamanders
as hypothyroid rather than athyroid.
Perhaps recent studies of Etkin and Gona (1967) may help in understanding the seeming inconsistencies of thyroid influences on newt limb
regeneration. They report that in frog tadpoles there is an antagonism
between thyroxine and prolactin; prolactin activity (on growth) is
greatest in premetamorphic stages but decreases to a minimum at
metamorphic climax. This behavior is the reciprocal of that for thyroxine.
To account for this they propose "that hypothalamic activity promotes
thyroid stimulating hormone secretion and inhibits prolactin secretion
by the tadpole's pituitary" (p. 257). The initiation of this hypothalamic
activity is thought to be by a positive feedback of thyroxine to the
hypothalamus. In Schmidt's experiments, could it be possible that the
prolonged hypothyroid state lifted the hypothalamic inhibition on the
secretion of prolactin which then could be released in large amounts to
stimulate limb regeneration? Thyroxine is most effective in restricting