THE STIMULUS TO HYPERTROPHIC GROWTH
103
nism of growth control in liver and kidney. The experimental obstacles
and uncertainties which have been outlined above have made very difficult
the design of experiments and the interpretation of the results. Moreover,
the many instances in the literature of conflicting reports of the outcome of
identical or very similar experiments suggest that there are additional
important variables which are not being controlled in the experiments
performed.
IV. Hypertrophic Liver Growth
A. A Morphological and Biochemical Description
The process of hypertrophic growth of the remnant of the mammalian
liver remaining after partial hepatectomy has been very thoroughly reviewed by Bucher (1963). We shall mention only those observations of the
process which seem relevant to a discussion of the control mechanism
involved. Unless otherwise stated, the term partial hepatectomy will mean
a 70% hepatectomy [median and left lateral lobes (Higgins and Anderson,
1931)].
Within a few days after partial hepatectomy in young rats the liver mass
grows back almost to equilibrium size, and after that there is a slower
growth over a period of weeks, often until the liver exceeds equilibrium size
calculated from body weight (Brues et al, 1936; Gurd et al., 1948). In mice
the process apparently occurs in an almost linear fashion until equilibrium
is reached (Tsuboi et al., 1954; Yokoyama et al., 1953). The rapidity of the
initial burst of proliferative activity in rat liver declines with age, as does
the final degree of restoration (Bucher and Glinos, 1950).
Above a certain threshold degree of hepatectomy, the intensity of the
hypertrophic response increases linearly with increasing degree of hepatectomy (MacDonald et al., 1962). In young rats the threshold is about
10% hepatectomy, but in adult rats it increases to 30% (Bucher and
Swaffield, 1962). The temporal response pattern varies with the age of rats
(Bucher et al, 1964).
The rate of RNA synthesis in the rat liver remnant increases linearly
for 6 hr after partial hepatectomy (Fujioka et al, 1963). According to Glinos
(1956) the elevation in rate of RNA synthesis begins in periportal areas
and spreads centrilobally. Tsukada and Lieberman (1964) have found
that small doses of actinomycin D and p-fluorophenylalanine, which do
not affect the RNA metabolism of normal cells, abolish the increase in
RNA synthesis which occurs after partial hepatectomy. The incorporation
of C
14
-leucine into protein is elevated, and the production of C
14
-carbon
dioxide is depressed in the perfused rat liver 48 hr after partial hepatectomy
(Staib and Miller, 1964). There are two peaks of uptake of labeled amino
103
nism of growth control in liver and kidney. The experimental obstacles
and uncertainties which have been outlined above have made very difficult
the design of experiments and the interpretation of the results. Moreover,
the many instances in the literature of conflicting reports of the outcome of
identical or very similar experiments suggest that there are additional
important variables which are not being controlled in the experiments
performed.
IV. Hypertrophic Liver Growth
A. A Morphological and Biochemical Description
The process of hypertrophic growth of the remnant of the mammalian
liver remaining after partial hepatectomy has been very thoroughly reviewed by Bucher (1963). We shall mention only those observations of the
process which seem relevant to a discussion of the control mechanism
involved. Unless otherwise stated, the term partial hepatectomy will mean
a 70% hepatectomy [median and left lateral lobes (Higgins and Anderson,
1931)].
Within a few days after partial hepatectomy in young rats the liver mass
grows back almost to equilibrium size, and after that there is a slower
growth over a period of weeks, often until the liver exceeds equilibrium size
calculated from body weight (Brues et al, 1936; Gurd et al., 1948). In mice
the process apparently occurs in an almost linear fashion until equilibrium
is reached (Tsuboi et al., 1954; Yokoyama et al., 1953). The rapidity of the
initial burst of proliferative activity in rat liver declines with age, as does
the final degree of restoration (Bucher and Glinos, 1950).
Above a certain threshold degree of hepatectomy, the intensity of the
hypertrophic response increases linearly with increasing degree of hepatectomy (MacDonald et al., 1962). In young rats the threshold is about
10% hepatectomy, but in adult rats it increases to 30% (Bucher and
Swaffield, 1962). The temporal response pattern varies with the age of rats
(Bucher et al, 1964).
The rate of RNA synthesis in the rat liver remnant increases linearly
for 6 hr after partial hepatectomy (Fujioka et al, 1963). According to Glinos
(1956) the elevation in rate of RNA synthesis begins in periportal areas
and spreads centrilobally. Tsukada and Lieberman (1964) have found
that small doses of actinomycin D and p-fluorophenylalanine, which do
not affect the RNA metabolism of normal cells, abolish the increase in
RNA synthesis which occurs after partial hepatectomy. The incorporation
of C
14
-leucine into protein is elevated, and the production of C
14
-carbon
dioxide is depressed in the perfused rat liver 48 hr after partial hepatectomy
(Staib and Miller, 1964). There are two peaks of uptake of labeled amino