AMPHIBIAN LIMB REGENERATION
239
necessitated some interruptions of the daily injections. Regeneration,
although minimal, was evidently not correlated with dose. Similar
injections of deoxycorticosterone (a mineralocorticoid) produced similar
results—delayed regenerative responses consisting of small blastemata.
Large numbers of the newts died and fewer than half survived beyond
20 days. Manner (1958) reported that 0.037 mg of cortisone acetate
injected daily into intact newts resulted in extensive degeneration of the
amputated limb. Williams (1959) injected a single dose of 4 mg of
cortisone acetate at the time of amputation into intact newts and reported
a delay of 4 to 6 days in limb regeneration. Twelve milligrams of cortisone acetate administered over a period of 3 to 4 weeks (1 mg every 2
days) resulted in a delay in regeneration of only 2 to 3 days compared to
saline-injected controls. Williams concluded that the newt can tolerate
high doses of cortisone without any appreciable effect on regeneration.
Bragdon and Dent (1954) injected 0.5 mg of cortisone acetate daily for
17 days into intact newts and observed no difference in limb regeneration rates, as compared to controls.
Schotte and Lindberg (1954) attempted a clarification of the problem
by means of adrenal transplantation. They implanted adrenal tissue of
Rana palustris
and Rana pipiens into hypophysectomized newts and
observed limb regeneration in half the cases. Interestingly, the best
regeneration (100% of cases) was obtained when the adrenal was
implanted 15 days after amputation, although amputation of a second
limb simultaneously with adrenal implantation may be a complication.
Schotte and Wilber (1958) transplanted adrenal tissue of R. pipiens into
both intact and hypophysectomized Rana clamitans adults. Regeneration, although atypical, was induced in the intact frogs but, surprisingly,
seven of eight limbs regenerated when adrenals were grafted into normal
host frogs at 40 and 47 days after amputation! Regeneration was abortive
in the hypophysectomized frogs; only about half the limbs developed a
regenerative response and this was merely of the nature of a small
accumulation blastema. Although the authors interpret this as being a
result of an absence of ACTH stimulation of the adrenal implants, other
pituitary growth factors are also missing and may be important. Furthermore, it is impossible to separate the adrenal gland of the frog from
kidney tissue so that, as Schotte and Wilber (1958) state, the stressor
effect of kidney tissue must also be considered. This suggestion is particularly pertinent since Johnson et al. (1967) have recently shown that
aldosterone (a mineralocorticoid) production can be significantly increased in hypophysectomized
bull frogs by infusion of renin and also
239
necessitated some interruptions of the daily injections. Regeneration,
although minimal, was evidently not correlated with dose. Similar
injections of deoxycorticosterone (a mineralocorticoid) produced similar
results—delayed regenerative responses consisting of small blastemata.
Large numbers of the newts died and fewer than half survived beyond
20 days. Manner (1958) reported that 0.037 mg of cortisone acetate
injected daily into intact newts resulted in extensive degeneration of the
amputated limb. Williams (1959) injected a single dose of 4 mg of
cortisone acetate at the time of amputation into intact newts and reported
a delay of 4 to 6 days in limb regeneration. Twelve milligrams of cortisone acetate administered over a period of 3 to 4 weeks (1 mg every 2
days) resulted in a delay in regeneration of only 2 to 3 days compared to
saline-injected controls. Williams concluded that the newt can tolerate
high doses of cortisone without any appreciable effect on regeneration.
Bragdon and Dent (1954) injected 0.5 mg of cortisone acetate daily for
17 days into intact newts and observed no difference in limb regeneration rates, as compared to controls.
Schotte and Lindberg (1954) attempted a clarification of the problem
by means of adrenal transplantation. They implanted adrenal tissue of
Rana palustris
and Rana pipiens into hypophysectomized newts and
observed limb regeneration in half the cases. Interestingly, the best
regeneration (100% of cases) was obtained when the adrenal was
implanted 15 days after amputation, although amputation of a second
limb simultaneously with adrenal implantation may be a complication.
Schotte and Wilber (1958) transplanted adrenal tissue of R. pipiens into
both intact and hypophysectomized Rana clamitans adults. Regeneration, although atypical, was induced in the intact frogs but, surprisingly,
seven of eight limbs regenerated when adrenals were grafted into normal
host frogs at 40 and 47 days after amputation! Regeneration was abortive
in the hypophysectomized frogs; only about half the limbs developed a
regenerative response and this was merely of the nature of a small
accumulation blastema. Although the authors interpret this as being a
result of an absence of ACTH stimulation of the adrenal implants, other
pituitary growth factors are also missing and may be important. Furthermore, it is impossible to separate the adrenal gland of the frog from
kidney tissue so that, as Schotte and Wilber (1958) state, the stressor
effect of kidney tissue must also be considered. This suggestion is particularly pertinent since Johnson et al. (1967) have recently shown that
aldosterone (a mineralocorticoid) production can be significantly increased in hypophysectomized
bull frogs by infusion of renin and also