96
BRIAN POOLE
polymerase system, DNA synthesis, or mitosis took place. These observations suggest that the immediate response of the kidney cells to a release
from organismic growth control is the rapid synthesis of cytoplasm and
that DNA synthesis and cell division follow secondarily upon the increase
of the cytoplasmic mass. As will be discussed below, the process of hypertrophic liver growth starts with RNA and protein synthesis and only later
does the synthesis of the DNA polymerase system, DNA synthesis, or cell
division occur.
Zumoff and Pachter (1964) have studied the growth of liver and kidney
in rats using simultaneous determinations of tissue mass and total number
of nuclei. In an inbred strain they found that tissue mass grew in close
proportion to body mass over most of the period of growth. There were
small changes in proportion when the rats were very small and then again
when they became very large. In male liver and in the kidneys of both
sexes the number of nuclei increased more slowly than tissue mass when the
rats were young (i.e., the cells were becoming larger), until puberty when
the increase in the number of nuclei ceased altogether and did not resume
until the animals had more than doubled their body weight. All this time
the tissue mass had been growing in strict proportion to body size (see Fig.
1). This mitotic arrest did not occur in gonadectomized animals but could
be produced in these animals by injections of sex hormones. Female liver
normally did not show mitotic arrest at puberty but the injection of testosterone produced the same arrest in the female livers as was observed in
the male livers.
The same authors studied in the same way the compensatory hypertrophy of the kidney remaining after unilateral nephrectomy. In normal
animals of 160 gm weight the renal hypertrophy which resulted was entirely
the result of cellular hypertrophy. There was no increase in the number of
nuclei in the organ. We see that in the liver and kidney tissue of these rats
the mitotic rate can be drastically modified by hormone treatment without
affecting the growth rate of the tissue. This important conclusion must be
borne in mind when we examine the experimental evidence supporting the
various theories of growth control.
II. Theories
A. Feedback Inhibition
There have been a number of different agents invoked in an attempt
to explain the regulation of normal growth and the stimulus to hypertrophic
growth. Weiss's theory of feedback inhibition of growth by freely diffusing
tissue-specific inhibitors is the most thorough and rigorous attempt to
explain the phenomena of growth control (Weiss, 1952). Briefly the theory
BRIAN POOLE
polymerase system, DNA synthesis, or mitosis took place. These observations suggest that the immediate response of the kidney cells to a release
from organismic growth control is the rapid synthesis of cytoplasm and
that DNA synthesis and cell division follow secondarily upon the increase
of the cytoplasmic mass. As will be discussed below, the process of hypertrophic liver growth starts with RNA and protein synthesis and only later
does the synthesis of the DNA polymerase system, DNA synthesis, or cell
division occur.
Zumoff and Pachter (1964) have studied the growth of liver and kidney
in rats using simultaneous determinations of tissue mass and total number
of nuclei. In an inbred strain they found that tissue mass grew in close
proportion to body mass over most of the period of growth. There were
small changes in proportion when the rats were very small and then again
when they became very large. In male liver and in the kidneys of both
sexes the number of nuclei increased more slowly than tissue mass when the
rats were young (i.e., the cells were becoming larger), until puberty when
the increase in the number of nuclei ceased altogether and did not resume
until the animals had more than doubled their body weight. All this time
the tissue mass had been growing in strict proportion to body size (see Fig.
1). This mitotic arrest did not occur in gonadectomized animals but could
be produced in these animals by injections of sex hormones. Female liver
normally did not show mitotic arrest at puberty but the injection of testosterone produced the same arrest in the female livers as was observed in
the male livers.
The same authors studied in the same way the compensatory hypertrophy of the kidney remaining after unilateral nephrectomy. In normal
animals of 160 gm weight the renal hypertrophy which resulted was entirely
the result of cellular hypertrophy. There was no increase in the number of
nuclei in the organ. We see that in the liver and kidney tissue of these rats
the mitotic rate can be drastically modified by hormone treatment without
affecting the growth rate of the tissue. This important conclusion must be
borne in mind when we examine the experimental evidence supporting the
various theories of growth control.
II. Theories
A. Feedback Inhibition
There have been a number of different agents invoked in an attempt
to explain the regulation of normal growth and the stimulus to hypertrophic
growth. Weiss's theory of feedback inhibition of growth by freely diffusing
tissue-specific inhibitors is the most thorough and rigorous attempt to
explain the phenomena of growth control (Weiss, 1952). Briefly the theory