238
CHARLES S. THORNTON
even when the injections were begun at 14 days after amputation and
hypophysectomy. Berman et al. (1964) point out, however, that the GH
(NIH) which Wilkerson used contained a significant prolactin contamination. Since these authors have shown that prolactin is an important
growth-stimulating agent in frog tadpoles, the possibility exists that the
prolactin contaminant stimulated the regeneration in Wilkerson's experiments. This suggestion is particularly cogent since Niwelinski (1958) had
previously found that limb regeneration was enhanced by injections of
prolactin into intact newts. Recently, we have found that prolactin will
support good limb regeneration when it is injected into hypophysectomized newts (Connelly et al., unpublished). These studies suggest an
important role of prolactin in adult newt limb regeneration, but do not
rule out a role of growth hormone.
Too little attention has been given, in regeneration studies, to the
interrelationship between the hypothalamus and the pituitary and to the
consequences of breaking this relation by removal of the pituitary to an
ectopic position. Thus ectopic pituitaries in the toad, Bujo, secrete little,
if any, ACTH, and hypophysectomized toads must be supplied with
exogenous ACTH to survive (van Dongen et al., 1966). The adult newt
ectopic pituitary has so far been found to synthesize only prolactin
(Masur, 1962; Grant and Cooper, 1965) and thyrotropin (Dent, 1966),
and ultrastructural studies of newt pituitaries correlate well with these
findings (Dent and Gupta, 1967). It may also be of interest, in this
connection, that Mangili et al. (1966) point out that the ectopic mammalian pituitary does not maintain adrenal weight in hypophysectomized
mammals nor will stress cause an increase in corticosterone secretion;
only when five ectopic pituitaries are present (Purnes and Sirett, 1967)
is there a significant elevation of plasma corticosterone (up to one-third
that of normal rats).
Schotte (1961, for review) has proposed that the stress of limb amputation triggers the release of ACTH from the pituitary which stimulates
increased synthesis and release of cortisone in the adrenal cortex. Cortisone is, according to this view, necessary for initiating the predominantly
epidermal type of wound healing associated with typical regeneration.
In the absence of this hormone activity, a thick dermal pad forms at the
stump tip and regeneration fails. Evidence for the involvement of
cortisone in the regeneration process is rather conflicting and confusing.
Schotte and Bierman (1956) injected cortisone (a glucocorticoid) into
hypophysectomized newts in daily amounts of 2.5 mg/ml; 1.25 mg/ml;
0.5 mg/ml or 0.25 mg/ml, although severity of reaction to the hormone
CHARLES S. THORNTON
even when the injections were begun at 14 days after amputation and
hypophysectomy. Berman et al. (1964) point out, however, that the GH
(NIH) which Wilkerson used contained a significant prolactin contamination. Since these authors have shown that prolactin is an important
growth-stimulating agent in frog tadpoles, the possibility exists that the
prolactin contaminant stimulated the regeneration in Wilkerson's experiments. This suggestion is particularly cogent since Niwelinski (1958) had
previously found that limb regeneration was enhanced by injections of
prolactin into intact newts. Recently, we have found that prolactin will
support good limb regeneration when it is injected into hypophysectomized newts (Connelly et al., unpublished). These studies suggest an
important role of prolactin in adult newt limb regeneration, but do not
rule out a role of growth hormone.
Too little attention has been given, in regeneration studies, to the
interrelationship between the hypothalamus and the pituitary and to the
consequences of breaking this relation by removal of the pituitary to an
ectopic position. Thus ectopic pituitaries in the toad, Bujo, secrete little,
if any, ACTH, and hypophysectomized toads must be supplied with
exogenous ACTH to survive (van Dongen et al., 1966). The adult newt
ectopic pituitary has so far been found to synthesize only prolactin
(Masur, 1962; Grant and Cooper, 1965) and thyrotropin (Dent, 1966),
and ultrastructural studies of newt pituitaries correlate well with these
findings (Dent and Gupta, 1967). It may also be of interest, in this
connection, that Mangili et al. (1966) point out that the ectopic mammalian pituitary does not maintain adrenal weight in hypophysectomized
mammals nor will stress cause an increase in corticosterone secretion;
only when five ectopic pituitaries are present (Purnes and Sirett, 1967)
is there a significant elevation of plasma corticosterone (up to one-third
that of normal rats).
Schotte (1961, for review) has proposed that the stress of limb amputation triggers the release of ACTH from the pituitary which stimulates
increased synthesis and release of cortisone in the adrenal cortex. Cortisone is, according to this view, necessary for initiating the predominantly
epidermal type of wound healing associated with typical regeneration.
In the absence of this hormone activity, a thick dermal pad forms at the
stump tip and regeneration fails. Evidence for the involvement of
cortisone in the regeneration process is rather conflicting and confusing.
Schotte and Bierman (1956) injected cortisone (a glucocorticoid) into
hypophysectomized newts in daily amounts of 2.5 mg/ml; 1.25 mg/ml;
0.5 mg/ml or 0.25 mg/ml, although severity of reaction to the hormone