THE STIMULUS TO HYPERTROPHIC GROWTH
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lobules in the hypertrophying liver appears to be a reorganization of cells,
secondary to the process of growth. The formation of new lobules is clearly
demonstrable only after repeated hepatectomies (G. E. C. Simpson and
Finckh, 1963). It is often said that kidney hypertrophy is a slow process of
compensatory growth resulting from functional overload, whereas liver
restoration is a rapid response to an unknown stimulus. Certainly there
is a difference in the rates of the two processes, but the source of the stimulus
is just as mysterious in the one case as it is in the other, and there is no
reason to suppose that the control mechanisms are qualitatively different.
For the purposes of theoretical discussion there is nothing to be gained by
considering the processes to be essentially different.
B. The Possibility of Humoral Feedback
We have shown the inadequacy of theories other than feedback inhibition to explain the phenomenon of hypertrophic growth. We have also reviewed a number of experimental results which seem to indicate that
growth control, especially in liver, is not mediated by humoral factors.
However it is important to consider the possibility of humoral factors in
the light of what we know about the time course of the hypertrophic respons?. In liver the elevation of RNA synthesis occurs almost immediately
after partial hepatectomy and reaches its maximum by 6 hr. This means
that by 6 hr the concentration of hypothetical inhibitors in the circulation
must have dropped to its lowest level. In fact, the change in inhibitor
concentration may be much faster than this, and we may be observing
merely the rate of response of the tissue. This means that, if growth inhibitors exist, they must have very short half-lives in the body fluids, and
an experimental change in inhibitor concentration would very soon be
corrected by synthesis or degradation. Under the circumstances it would be
exceedingly difficult to demonstrate the action of humoral factors by direct
means.
In kidney the hypertrophic response is much slower, but there is no
way of knowing whether the delay is in the growth stimulus or in the tissue
response. If the delay were in the stimulus, we might expect that it would be
easier to demonstrate the action of humoral factors in kidney than in liver.
If the delay were in the tissue response, demonstration of humoral factors
might be much more difficult.
In any case we may surmise that the actual process of growth control
and stimulation to hypertrophic growth is very complicated and may
involve more than one feedback loop. There are so many unknowns in any
experimental situation that we cannot exclude the possibility of humoral
feedback on the basis of results so far reported. It remains the only unified
theory capable of accounting for the phenomena.
115
lobules in the hypertrophying liver appears to be a reorganization of cells,
secondary to the process of growth. The formation of new lobules is clearly
demonstrable only after repeated hepatectomies (G. E. C. Simpson and
Finckh, 1963). It is often said that kidney hypertrophy is a slow process of
compensatory growth resulting from functional overload, whereas liver
restoration is a rapid response to an unknown stimulus. Certainly there
is a difference in the rates of the two processes, but the source of the stimulus
is just as mysterious in the one case as it is in the other, and there is no
reason to suppose that the control mechanisms are qualitatively different.
For the purposes of theoretical discussion there is nothing to be gained by
considering the processes to be essentially different.
B. The Possibility of Humoral Feedback
We have shown the inadequacy of theories other than feedback inhibition to explain the phenomenon of hypertrophic growth. We have also reviewed a number of experimental results which seem to indicate that
growth control, especially in liver, is not mediated by humoral factors.
However it is important to consider the possibility of humoral factors in
the light of what we know about the time course of the hypertrophic respons?. In liver the elevation of RNA synthesis occurs almost immediately
after partial hepatectomy and reaches its maximum by 6 hr. This means
that by 6 hr the concentration of hypothetical inhibitors in the circulation
must have dropped to its lowest level. In fact, the change in inhibitor
concentration may be much faster than this, and we may be observing
merely the rate of response of the tissue. This means that, if growth inhibitors exist, they must have very short half-lives in the body fluids, and
an experimental change in inhibitor concentration would very soon be
corrected by synthesis or degradation. Under the circumstances it would be
exceedingly difficult to demonstrate the action of humoral factors by direct
means.
In kidney the hypertrophic response is much slower, but there is no
way of knowing whether the delay is in the growth stimulus or in the tissue
response. If the delay were in the stimulus, we might expect that it would be
easier to demonstrate the action of humoral factors in kidney than in liver.
If the delay were in the tissue response, demonstration of humoral factors
might be much more difficult.
In any case we may surmise that the actual process of growth control
and stimulation to hypertrophic growth is very complicated and may
involve more than one feedback loop. There are so many unknowns in any
experimental situation that we cannot exclude the possibility of humoral
feedback on the basis of results so far reported. It remains the only unified
theory capable of accounting for the phenomena.