38
THOMAS S. ARGYRIS
Specificity of the stimulus mechanism appears to be, at least superficially, different in wound healing and in compensatory hypertrophy. The
evidence we have summarized indicates that damage-induced growth has
considerable tissue specificity. One can damage, e.g., hair follicles in the
skin, and not initiate cell proliferation of the overlying epidermis
(Bullough and Laurence, 1960a). Compensatory hypertrophy, on the
other hand, involves proliferation of all the tissues of an organ. Of course
this may simply owe to the fact that the loss of mass involves losses from
all tissues of an organ. In liver compensatory hypertrophy after partial
hepatectomy, Abercrombie and Harkness (1951) have shown that hepatocyte cell proliferation precedes cell proliferation of the bile duct and
littoral cells. They have suggested that the stimulus for hepatocyte
proliferation may act as a lead stimulus which, in turn, triggers the
mitotic proliferation of the other cell populations. Other explanations
such as there being one stimulus but different cell sensitivities are not
ruled out (Abercrombie, 1957; Harkness, 1957). In any case, the evidence
suggests that in compensatory hypertrophy one stimulus is sufficient to
result in the growth of all the tissues. Last, and perhaps of most importance, is the fact that compensatory hypertrophy is obviously initiated
by the loss of mass, whereas the loss of mass is probably not the stimulus
mechanism in wound healing (Argyris and Trimble, 1964a,b). Thus the
evidence clearly points out significant differences between wound healing
and compensatory hypertrophy. It is our working hypothesis that these
differences suggest that the mechanisms for initiating growth in damage
and in compensatory hypertrophy are different. But we are not committed to this notion and keep an open mind.
One possible unifying idea for the initiations of growth in wound
healing and in compensatory hypertrophy is that of Tsanev (1963).
Tsanev and Markov (1964) have presented evidence that within an hour
after partial hepatectomy there is a decrease in cytoplasmic RNA that is
followed by a subsequent increase in RNA. This initial effect on RNA is
precisely the same as that Tsanev (1963) suggests occurs in epidermal
damage, as we have already discussed in Section IV,B. The initial decrease in RNA in both cases is, presumably, brought about by the action
of a microsomal ribonuclease. How the microsomal ribonuclease is released is unknown. In the case of liver regeneration it may somehow arise
from the intial excess of substrates that the cells in the remaining liver
are faced with immediately after partial hepatectomy (Tsanev, 1966).
The breakdown of cytoplasmic RNA is probably an index of the breakdown and disorganization of the ribosomal or polysomal units in the
THOMAS S. ARGYRIS
Specificity of the stimulus mechanism appears to be, at least superficially, different in wound healing and in compensatory hypertrophy. The
evidence we have summarized indicates that damage-induced growth has
considerable tissue specificity. One can damage, e.g., hair follicles in the
skin, and not initiate cell proliferation of the overlying epidermis
(Bullough and Laurence, 1960a). Compensatory hypertrophy, on the
other hand, involves proliferation of all the tissues of an organ. Of course
this may simply owe to the fact that the loss of mass involves losses from
all tissues of an organ. In liver compensatory hypertrophy after partial
hepatectomy, Abercrombie and Harkness (1951) have shown that hepatocyte cell proliferation precedes cell proliferation of the bile duct and
littoral cells. They have suggested that the stimulus for hepatocyte
proliferation may act as a lead stimulus which, in turn, triggers the
mitotic proliferation of the other cell populations. Other explanations
such as there being one stimulus but different cell sensitivities are not
ruled out (Abercrombie, 1957; Harkness, 1957). In any case, the evidence
suggests that in compensatory hypertrophy one stimulus is sufficient to
result in the growth of all the tissues. Last, and perhaps of most importance, is the fact that compensatory hypertrophy is obviously initiated
by the loss of mass, whereas the loss of mass is probably not the stimulus
mechanism in wound healing (Argyris and Trimble, 1964a,b). Thus the
evidence clearly points out significant differences between wound healing
and compensatory hypertrophy. It is our working hypothesis that these
differences suggest that the mechanisms for initiating growth in damage
and in compensatory hypertrophy are different. But we are not committed to this notion and keep an open mind.
One possible unifying idea for the initiations of growth in wound
healing and in compensatory hypertrophy is that of Tsanev (1963).
Tsanev and Markov (1964) have presented evidence that within an hour
after partial hepatectomy there is a decrease in cytoplasmic RNA that is
followed by a subsequent increase in RNA. This initial effect on RNA is
precisely the same as that Tsanev (1963) suggests occurs in epidermal
damage, as we have already discussed in Section IV,B. The initial decrease in RNA in both cases is, presumably, brought about by the action
of a microsomal ribonuclease. How the microsomal ribonuclease is released is unknown. In the case of liver regeneration it may somehow arise
from the intial excess of substrates that the cells in the remaining liver
are faced with immediately after partial hepatectomy (Tsanev, 1966).
The breakdown of cytoplasmic RNA is probably an index of the breakdown and disorganization of the ribosomal or polysomal units in the