105
BRIAN POOLE
Peters (1962) has reported that the mitotic index in hypertrophying rat
liver is increased by exposure of the animals to low external temperatures
and is reduced by exposure to high temperatures. Injections of thyroxine
had the same effect as low temperatures in increasing the mitotic index.
Temperature stress results in a complicated pattern of change in hormone
balance and metabolic rates and usually in a change in internal temperature
(Przibram, 1923). Consequently, it is impossible to decide how the changes
reported in mitotic index are brought about, but these observations illustrate the dependence of the process of liver restoration upon the physiological state of the whole animal. Thyroidectomy has no effect on the rate
of liver hypertrophy (Christensen and Jacobsen, 1949; Rapport et al.,
1948), but feeding thyroxine increases the rate (Rapport et al., 1948).
Ovariectomy 2 weeks before partial hepatectomy results in a small lag
in lipid accumulation in the liver remnant and perhaps a small increase in
water content initially (Szego and Roberts, 1949). Unilateral nephrectomy
has been reported to have a small inhibitory effect on liver growth (Badran
and Echave Llanos, 1963), whereas repeated injections of histamine reportedly increase liver weight in rats (Molimard, 1960). These effects are
probably all related to changes in the general rate of body metabolism and
have nothing to do with the control mechanism we are discussing, but they
do point up the difficulties in designing adequately controlled experiments.
The roles of the pituitary and the adrenal cortex in liver growth are more
complex. When partial hepatectomy is performed after hypophysectomy
there is a reduced level of mitotic activity in the liver remnant (Bilge and
Meschan, 1963; Wrba et al, 1964). The injection of pituitary growth
hormone or crude pituitary extract is reported to increase the rate of liver
hypertrophy, but there is some difference in the effect on the mitotic rate
between the purified and crude preparations (Cater et al, 1957; Echave
Llanos and Russo, 1964). Adrenalectomy at the same time as partial
hepatectomy is followed by somewhat reduced mitotic activity in the liver
remnant, but fat deposition occurs normally (Berman et al, 1947; Rapport
et al, 1948). The injection of adrenocorticotropin (ACTH) or adrenocortical
extract into partially hepatectomized rats increases the mitotic index in
the liver remnant and prevents the drop in serum proteins which normally
occurs (Roberts, 1952). Thus the pituitary and the adrenal cortex seem to
be secreting something that stimulates the hypertrophic process. However,
in a hypophysectomized, partially hepatectomized rat, the injection of
pituitary growth hormone or crude pituitary extract has no effect on the
rate of liver hypertrophy, and the injection of cortisone causes degenerative
changes in the liver cells. The injection of both cortisone and pituitary
growth hormone results in elevated mitotic activity in the liver remnant
(Hemingway and Cater, 1958). It appears that the normal process of liver
BRIAN POOLE
Peters (1962) has reported that the mitotic index in hypertrophying rat
liver is increased by exposure of the animals to low external temperatures
and is reduced by exposure to high temperatures. Injections of thyroxine
had the same effect as low temperatures in increasing the mitotic index.
Temperature stress results in a complicated pattern of change in hormone
balance and metabolic rates and usually in a change in internal temperature
(Przibram, 1923). Consequently, it is impossible to decide how the changes
reported in mitotic index are brought about, but these observations illustrate the dependence of the process of liver restoration upon the physiological state of the whole animal. Thyroidectomy has no effect on the rate
of liver hypertrophy (Christensen and Jacobsen, 1949; Rapport et al.,
1948), but feeding thyroxine increases the rate (Rapport et al., 1948).
Ovariectomy 2 weeks before partial hepatectomy results in a small lag
in lipid accumulation in the liver remnant and perhaps a small increase in
water content initially (Szego and Roberts, 1949). Unilateral nephrectomy
has been reported to have a small inhibitory effect on liver growth (Badran
and Echave Llanos, 1963), whereas repeated injections of histamine reportedly increase liver weight in rats (Molimard, 1960). These effects are
probably all related to changes in the general rate of body metabolism and
have nothing to do with the control mechanism we are discussing, but they
do point up the difficulties in designing adequately controlled experiments.
The roles of the pituitary and the adrenal cortex in liver growth are more
complex. When partial hepatectomy is performed after hypophysectomy
there is a reduced level of mitotic activity in the liver remnant (Bilge and
Meschan, 1963; Wrba et al, 1964). The injection of pituitary growth
hormone or crude pituitary extract is reported to increase the rate of liver
hypertrophy, but there is some difference in the effect on the mitotic rate
between the purified and crude preparations (Cater et al, 1957; Echave
Llanos and Russo, 1964). Adrenalectomy at the same time as partial
hepatectomy is followed by somewhat reduced mitotic activity in the liver
remnant, but fat deposition occurs normally (Berman et al, 1947; Rapport
et al, 1948). The injection of adrenocorticotropin (ACTH) or adrenocortical
extract into partially hepatectomized rats increases the mitotic index in
the liver remnant and prevents the drop in serum proteins which normally
occurs (Roberts, 1952). Thus the pituitary and the adrenal cortex seem to
be secreting something that stimulates the hypertrophic process. However,
in a hypophysectomized, partially hepatectomized rat, the injection of
pituitary growth hormone or crude pituitary extract has no effect on the
rate of liver hypertrophy, and the injection of cortisone causes degenerative
changes in the liver cells. The injection of both cortisone and pituitary
growth hormone results in elevated mitotic activity in the liver remnant
(Hemingway and Cater, 1958). It appears that the normal process of liver