640
I L S E
L A S N I T Z K I
fibroblasts. Vogelaar and Erlichman (1936) and Verne and Odiette
(1936) reported that fibroblasts from human thyroid and embryonicchick heart were not affected by the addition of thyroxine to the medium
over a wide range of concentrations, while Latta and Davis (1938)
obtained a temporary stimulation of growth in heart-fibroblasts of
chick and rat after small doses, and an inhibition of growth after
higher concentrations.
Semura (1931) demonstrated in detailed experiments that low concentrations of the hormone consistently stimulated the growth of chickheart fibroblasts while higher doses inhibited it. This result was confirmed by von Haam and Cappel (1940) on cultures of mouse-heart
fibroblasts grown in Carrel flasks and as coverslip cultures. Dilutions
of 10~
7
-10~
9 (sic) increased the mitotic index and the area of outgrowth
but dilutions of 10~
5 diminished both; the number of cell divisions
was increased to a greater degree than the size of outgrowth.
Results by Martius and Hess (1959) suggest that the action of thyroxine on cell growth may be due to a disturbance of oxidative phosphorylation. Incubation of liver mitochondria with 1 0
- 4 and 10~
5
M thyroxine
resulted in an uncoupling of respiration and phosphorylation, but a
reversal of this effect was seen after long term incubation with lower
concentrations (10~
6
M) of the hormone. Leslie and Sinclair (1959)
found that thyroxine ( T 4 ) and triiodothyronine ( T 3 ) inhibited the
growth of freshly explanted human lung cells but did not affect the proliferation of human foetal liver and kidney cells nor that of Hep
1 and Hep 2 carcinoma cells which had been grown in vitro for
many years. The authors attribute this difference to the fact that T 4
and T 3 do not uncouple the oxidative phosphorylation in the long
established cell strains which have lost their original oxidative activity.
This result demonstrates clearly that the differential response does
not depend on whether the cells are derived from normal or malignant
cells but is due to a change in enzyme pattern occurring in both types
of cells during prolonged cultivation.
B . E F F E C T S O N O R G A N
C U L T U R E S
O F
B O N E
It has long been recognized that the thyroid influences the growth
and structure of bone and that both deficiency and excess of thyroxine
produce skeletal abnormalities. Clinical evidence showed that osteoporosis is frequently found in hyperthyroidism (Plummer, 1928;
Hunter, 1930).
Skeletal growth was influenced experimentally in laboratory animals
by administration of thyroxine. Dott (1923) described acceleration of
epiphyseal growth in hyperthyroidal kittens and puppies. He found an
I L S E
L A S N I T Z K I
fibroblasts. Vogelaar and Erlichman (1936) and Verne and Odiette
(1936) reported that fibroblasts from human thyroid and embryonicchick heart were not affected by the addition of thyroxine to the medium
over a wide range of concentrations, while Latta and Davis (1938)
obtained a temporary stimulation of growth in heart-fibroblasts of
chick and rat after small doses, and an inhibition of growth after
higher concentrations.
Semura (1931) demonstrated in detailed experiments that low concentrations of the hormone consistently stimulated the growth of chickheart fibroblasts while higher doses inhibited it. This result was confirmed by von Haam and Cappel (1940) on cultures of mouse-heart
fibroblasts grown in Carrel flasks and as coverslip cultures. Dilutions
of 10~
7
-10~
9 (sic) increased the mitotic index and the area of outgrowth
but dilutions of 10~
5 diminished both; the number of cell divisions
was increased to a greater degree than the size of outgrowth.
Results by Martius and Hess (1959) suggest that the action of thyroxine on cell growth may be due to a disturbance of oxidative phosphorylation. Incubation of liver mitochondria with 1 0
- 4 and 10~
5
M thyroxine
resulted in an uncoupling of respiration and phosphorylation, but a
reversal of this effect was seen after long term incubation with lower
concentrations (10~
6
M) of the hormone. Leslie and Sinclair (1959)
found that thyroxine ( T 4 ) and triiodothyronine ( T 3 ) inhibited the
growth of freshly explanted human lung cells but did not affect the proliferation of human foetal liver and kidney cells nor that of Hep
1 and Hep 2 carcinoma cells which had been grown in vitro for
many years. The authors attribute this difference to the fact that T 4
and T 3 do not uncouple the oxidative phosphorylation in the long
established cell strains which have lost their original oxidative activity.
This result demonstrates clearly that the differential response does
not depend on whether the cells are derived from normal or malignant
cells but is due to a change in enzyme pattern occurring in both types
of cells during prolonged cultivation.
B . E F F E C T S O N O R G A N
C U L T U R E S
O F
B O N E
It has long been recognized that the thyroid influences the growth
and structure of bone and that both deficiency and excess of thyroxine
produce skeletal abnormalities. Clinical evidence showed that osteoporosis is frequently found in hyperthyroidism (Plummer, 1928;
Hunter, 1930).
Skeletal growth was influenced experimentally in laboratory animals
by administration of thyroxine. Dott (1923) described acceleration of
epiphyseal growth in hyperthyroidal kittens and puppies. He found an