THE STIMULUS TO HYPERTROPHIC GROWTH
105
hepatectomy. Similar vacuoles are seen during anoxia. This is the earliest
reported response to partial hepatectomy, but it may have nothing to do
with the hypertrophic response.
Recent electron-microscope studies of hypertrophying liver of the rat
(Jordan, 1964) and of the mouse (Trotter, 1964) tend to confirm the biochemical analyses reported above. Fat droplets become more numerous
in the cytoplasm in the earliest samples of tissue examined (1 hr after partial
hepatectomy). Glycogen particles are reduced. Small (30-100 ιημ) osmophilic bodies become numerous in the cytoplasm soon after the operation,
but decrease in number as fat droplets become abundant.
No biochemical or histological differences have been detected between
normal and fully restored liver except for persisting increased polyploidy.
The report of Ingle (1954) that rats which have completely recovered from
an 80% hepatectomy are unable to withstand such an extensive hepatectomy again suggests that there may be some difference in the new
tissue.
In summary, it appears that the response to partial hepatectomy of
the remaining liver tissue starts almost immediately, with an increase in
the rate of RNA and protein synthesis and a concomitant depletion of liver
glycogen. Body fat is mobilized and accumulated in the liver. After a period
of protein synthesis, the enzymes necessary for DNA synthesis are produced
(synthesized or activated), then DNA synthesis and mitotic activity
follows. This increased metabolic activity still shows the diurnal rhythm
found in normal tissue. The metabolic stimulus is specific to liver (D. P.
Simpson, 1961b).
B. Factors Influencing the Hypertrophic Response
There are many factors affecting the rate of liver restoration which are
probably not related to the stimulus to hypertrophic growth or the normal
control mechanism of liver growth. The liver of rats on balanced diets
hypertrophies more rapidly than that of rats on unbalanced diets, even if
protein is in excess (Stone, 1935). Force feeding increases the rate of hypertrophy, as does the addition of powdered liver to the diet (Machella et al.,
1940; Newman et al., 1949). Starvation does not significantly reduce the
initial hypertrophic response (Galamin Ligori et al., 1962). In fact, Gurd
et al. (1948) reported that the initial gain in liver weight after partial
hepatectomy is greater in starved rats than it is in controls. The weight
gain on the first day is mostly fat. Even rats on diets that cause cirrhosis
show the hypertrophic response (R. B. Williams, 1951). Clerici et al. (1954)
have shown that sympathetic denervation of the liver has no effect on the
hypertrophic response to partial hepatectomy.
105
hepatectomy. Similar vacuoles are seen during anoxia. This is the earliest
reported response to partial hepatectomy, but it may have nothing to do
with the hypertrophic response.
Recent electron-microscope studies of hypertrophying liver of the rat
(Jordan, 1964) and of the mouse (Trotter, 1964) tend to confirm the biochemical analyses reported above. Fat droplets become more numerous
in the cytoplasm in the earliest samples of tissue examined (1 hr after partial
hepatectomy). Glycogen particles are reduced. Small (30-100 ιημ) osmophilic bodies become numerous in the cytoplasm soon after the operation,
but decrease in number as fat droplets become abundant.
No biochemical or histological differences have been detected between
normal and fully restored liver except for persisting increased polyploidy.
The report of Ingle (1954) that rats which have completely recovered from
an 80% hepatectomy are unable to withstand such an extensive hepatectomy again suggests that there may be some difference in the new
tissue.
In summary, it appears that the response to partial hepatectomy of
the remaining liver tissue starts almost immediately, with an increase in
the rate of RNA and protein synthesis and a concomitant depletion of liver
glycogen. Body fat is mobilized and accumulated in the liver. After a period
of protein synthesis, the enzymes necessary for DNA synthesis are produced
(synthesized or activated), then DNA synthesis and mitotic activity
follows. This increased metabolic activity still shows the diurnal rhythm
found in normal tissue. The metabolic stimulus is specific to liver (D. P.
Simpson, 1961b).
B. Factors Influencing the Hypertrophic Response
There are many factors affecting the rate of liver restoration which are
probably not related to the stimulus to hypertrophic growth or the normal
control mechanism of liver growth. The liver of rats on balanced diets
hypertrophies more rapidly than that of rats on unbalanced diets, even if
protein is in excess (Stone, 1935). Force feeding increases the rate of hypertrophy, as does the addition of powdered liver to the diet (Machella et al.,
1940; Newman et al., 1949). Starvation does not significantly reduce the
initial hypertrophic response (Galamin Ligori et al., 1962). In fact, Gurd
et al. (1948) reported that the initial gain in liver weight after partial
hepatectomy is greater in starved rats than it is in controls. The weight
gain on the first day is mostly fat. Even rats on diets that cause cirrhosis
show the hypertrophic response (R. B. Williams, 1951). Clerici et al. (1954)
have shown that sympathetic denervation of the liver has no effect on the
hypertrophic response to partial hepatectomy.