THE STIMULUS TO HYPERTROPHIC GROWTH
109
Glinos (1958) reported that if the serum of a rat is partially replaced
with saline solution, there is a substantial increase in the mitotic activity
of the liver. Fluid restriction has the opposite effect. From these results
and the fact that serum proteins, especially albumins, are reduced after
hepatectomy, Glinos theorized that liver growth is inhibited by serum
albumin. He explained the immediate effects of partial hepatectomy as
the result of increased blood pressure in the liver which was supposed to
cause increased transudation of water into the intercellular space with
a local dilution of albumin concentration. Brauer (1963) has objected to
this theory on hemodynamic grounds. There is one recent report that injections of serum albumin inhibit normal and hypertrophic liver growth
(Survis et al, 1962). However, nephrotic humans sometimes live for years
spilling albumin in their urine without noticeable hepatomegaly. Rogers et
al. (1961) report that they have been unable to repeat Glinos
, experiments.
There have been a number of experiments in which the effects of macerates or crude extracts of liver have been tested on normal or hypertrophying
liver. These extracts inhibited (Molimard, 1959; Saetren, 1956; Stich and
Florian, 1958), had no effect (Malmgren, 1956; Christensen and Jacobsen,
1949), or stimulated (Andres, 1955; Blomqvist, 1957; Formijne, 1955;
Lahtiharju, 1961; Lahtiharju and Teir, 1964; Paschkis et al., 1957; McJudkin and Breuhaus, 1931; Teir and Ravanti, 1953; Tumanishvili, 1960)
mitotic activity or DNA synthesis. Wilson and Leduc (1947) found a
complex effect involving both stimulation and inhibition following injections of liver macerate or other protein concentrates. One explanation of
the contradictions in the effects reported comes from the observation of
Echave Llanos and Bordin (1963), who injected the same liver homogenates
into mice at various times of day. When the injection was given in the
evening, mitotic activity was inhibited; an injection at midnight had no
effect, whereas an injection in the morning stimulated mitotic activity.
There are reports of mitotic stimulation in liver by injections of liver
chromatin (Marshak and Walker, 1945; Yashina, 1964) and of growth inhibition by the acetone-insoluble, ether-soluble fraction of liver (Molimard,
1959). These effects may or may not have anything to do with the mechanism of liver growth control, and, until a more thorough study is made
of the nature of the effect over a period of time and of the fraction of the
extract responsible for the effect, there will be no way of judging the significance of the phenomena reported.
The livers of tumor-bearing rats and mice are larger than those of controls (Annau et ah, 1951), but the ratio of the liver mass to the mass of the
animal plus tumor is the same as the ratio of liver mass to body mass of
controls (Naora and Naora, 1964). This finding is consistent with the theory
of humoral feedback control of liver growth. The reported increased re-
109
Glinos (1958) reported that if the serum of a rat is partially replaced
with saline solution, there is a substantial increase in the mitotic activity
of the liver. Fluid restriction has the opposite effect. From these results
and the fact that serum proteins, especially albumins, are reduced after
hepatectomy, Glinos theorized that liver growth is inhibited by serum
albumin. He explained the immediate effects of partial hepatectomy as
the result of increased blood pressure in the liver which was supposed to
cause increased transudation of water into the intercellular space with
a local dilution of albumin concentration. Brauer (1963) has objected to
this theory on hemodynamic grounds. There is one recent report that injections of serum albumin inhibit normal and hypertrophic liver growth
(Survis et al, 1962). However, nephrotic humans sometimes live for years
spilling albumin in their urine without noticeable hepatomegaly. Rogers et
al. (1961) report that they have been unable to repeat Glinos
, experiments.
There have been a number of experiments in which the effects of macerates or crude extracts of liver have been tested on normal or hypertrophying
liver. These extracts inhibited (Molimard, 1959; Saetren, 1956; Stich and
Florian, 1958), had no effect (Malmgren, 1956; Christensen and Jacobsen,
1949), or stimulated (Andres, 1955; Blomqvist, 1957; Formijne, 1955;
Lahtiharju, 1961; Lahtiharju and Teir, 1964; Paschkis et al., 1957; McJudkin and Breuhaus, 1931; Teir and Ravanti, 1953; Tumanishvili, 1960)
mitotic activity or DNA synthesis. Wilson and Leduc (1947) found a
complex effect involving both stimulation and inhibition following injections of liver macerate or other protein concentrates. One explanation of
the contradictions in the effects reported comes from the observation of
Echave Llanos and Bordin (1963), who injected the same liver homogenates
into mice at various times of day. When the injection was given in the
evening, mitotic activity was inhibited; an injection at midnight had no
effect, whereas an injection in the morning stimulated mitotic activity.
There are reports of mitotic stimulation in liver by injections of liver
chromatin (Marshak and Walker, 1945; Yashina, 1964) and of growth inhibition by the acetone-insoluble, ether-soluble fraction of liver (Molimard,
1959). These effects may or may not have anything to do with the mechanism of liver growth control, and, until a more thorough study is made
of the nature of the effect over a period of time and of the fraction of the
extract responsible for the effect, there will be no way of judging the significance of the phenomena reported.
The livers of tumor-bearing rats and mice are larger than those of controls (Annau et ah, 1951), but the ratio of the liver mass to the mass of the
animal plus tumor is the same as the ratio of liver mass to body mass of
controls (Naora and Naora, 1964). This finding is consistent with the theory
of humoral feedback control of liver growth. The reported increased re-