THE STIMULUS TO HYPERTROPHIC GROWTH
90
antitemplates secreted by each tissue to the total body volume becomes
smaller as growth progresses.
This theory has been given mathematical form and applied to the growth
of the whole chick by Weiss and Kavanau (1957). It is considered that the
mass of any tissue can be analyzed into two components—the generative
mass and the differentiated mass. The generative mass comprises that
portion of the tissue mass involved in the growth process. Thus the amount
of generative mass is a measure of the tissue's capacity for growth. The
generative mass is increased by growth and decreased by conversion of
generative into differentiated mass, a process which must also be under
feedback control. The differentiated mass makes up the rest of the tissue.
Catabolic processes tend to reduce both components of the tissue mass
When the theoretical function derived from these assumptions is fitted to
the empirical curve for chick growth the biological parameters determined
in this way all have reasonable values.
Weiss and Kavanau also applied their theoretical growth function to
the hypothetical reduction of the mass of a particular tissue by one-half
and by three-quarters. The two important parameters which determine
the temporal pattern of response to this treatment are the half-life of the
inhibitors in the body fluids and the number of inhibitors necessary to
inactivate one binding site. The shorter the inhibitor half-life, the faster
the inhibitor concentration will drop after the experimental reduction of
tissue mass and the sooner the hypertrophic response will occur. The
greater the number of inhibitor molecules required to inactivate one acceptor site, the more sensitive the growth rate will be to small changes in
inhibitor concentration. (If η is the number of inhibitor molecules necessary
to inactivate one binding site and / is the inhibitor concentration, then
the ratio of bound to free binding sites will be proportional to /
n .) By using
various assumptions about the values of these two parameters, Weiss and
Kavanau plotted a number of response curves and concluded that a model
which was sufficiently sensitive to changes in the inhibitor level, without
being excessively unstable, could be produced if one assumed that on the
average two inhibitors are required to inactivate each binding site.
In more recent papers (Kavanau, 1960, 1961, 1964), the implications
of the growth function have been explored by digital computer for the case
of compensatory hypertrophy of a tissue mass in animals of various ages,
with a wide variety of combinations of order of inhibition and half-life of
inhibitors.
The theoretical curve of tissue mass restoration has the form of a damped
oscillation which in some cases involves a significant secondary spurt of
growth after a number of days, like that which has been reported for
hypertrophying rat liver. In all cases there is a certain amount of overshoot
90
antitemplates secreted by each tissue to the total body volume becomes
smaller as growth progresses.
This theory has been given mathematical form and applied to the growth
of the whole chick by Weiss and Kavanau (1957). It is considered that the
mass of any tissue can be analyzed into two components—the generative
mass and the differentiated mass. The generative mass comprises that
portion of the tissue mass involved in the growth process. Thus the amount
of generative mass is a measure of the tissue's capacity for growth. The
generative mass is increased by growth and decreased by conversion of
generative into differentiated mass, a process which must also be under
feedback control. The differentiated mass makes up the rest of the tissue.
Catabolic processes tend to reduce both components of the tissue mass
When the theoretical function derived from these assumptions is fitted to
the empirical curve for chick growth the biological parameters determined
in this way all have reasonable values.
Weiss and Kavanau also applied their theoretical growth function to
the hypothetical reduction of the mass of a particular tissue by one-half
and by three-quarters. The two important parameters which determine
the temporal pattern of response to this treatment are the half-life of the
inhibitors in the body fluids and the number of inhibitors necessary to
inactivate one binding site. The shorter the inhibitor half-life, the faster
the inhibitor concentration will drop after the experimental reduction of
tissue mass and the sooner the hypertrophic response will occur. The
greater the number of inhibitor molecules required to inactivate one acceptor site, the more sensitive the growth rate will be to small changes in
inhibitor concentration. (If η is the number of inhibitor molecules necessary
to inactivate one binding site and / is the inhibitor concentration, then
the ratio of bound to free binding sites will be proportional to /
n .) By using
various assumptions about the values of these two parameters, Weiss and
Kavanau plotted a number of response curves and concluded that a model
which was sufficiently sensitive to changes in the inhibitor level, without
being excessively unstable, could be produced if one assumed that on the
average two inhibitors are required to inactivate each binding site.
In more recent papers (Kavanau, 1960, 1961, 1964), the implications
of the growth function have been explored by digital computer for the case
of compensatory hypertrophy of a tissue mass in animals of various ages,
with a wide variety of combinations of order of inhibition and half-life of
inhibitors.
The theoretical curve of tissue mass restoration has the form of a damped
oscillation which in some cases involves a significant secondary spurt of
growth after a number of days, like that which has been reported for
hypertrophying rat liver. In all cases there is a certain amount of overshoot