16. A C T I O N S OF H O R M O N E S
615
containing hydrocortisone, the vitamin A effect was diminished in
both media, but to a greater degree in the medium containing hydrocortisone. The degree of recovery also varied with individual bones:
for instance, mouse radii and ulnae continued to disintegrate, while
the tibiae recovered partially.
Although cortisone and hydrocortisone show a similar effect on bone
growth in vivo and in vitro the retardation of the vitamin A effect by
hydrocortisone is strikingly different from that in vivo, where it is potentiated by the hormone (Selye, 1958). This is probably due to a release
of stored vitamin A from the liver under the influence of hydrocortisone
(Clark and Colburn, 1955). It is likely that the effect of the hormone
on cultures involves a different mechanism. Vitamin A releases an
acid protease from the chondrocytes which digests the matrix (Dingle,
1961) and it is possible that hydrocortisone inhibits the synthesis or
release of this enzyme. The same mechanism would also explain the
inhibition of the vitamin A effect on the epidermis.
3. Summary
The results show that corticosteroids directly affect various parameters of growth and differentiation and that in each instance different
mechanisms seem to be responsible. High doses severely damage or
inhibit the proliferation of cells—in particular, those derived from the
connective tissue including lymphocytes and melanophores—while
endothelium seems more resistant to the agent. This inhibition is
bound up with a reduction of respiration combined with a rise of
glycolysis in the treated cells. Low doses, on the other hand, increase
both respiration and cell proliferation. Intermediate concentrations
of the hormone which, when applied alone, were ineffective, increased
the growth-promoting effect of insulin on chick-heart fibroblasts, and
reversed the inhibition of growth seen after application of growth
hormone.
The retardation of growth observed in embryonic limb-bone
rudiments is not due to an inhibition of cell proliferation but to a
disturbance of cartilage formation, probably brought about by an
inhibition of chondroitin sulphate synthesis.
The mitigation of u.v. burns in embryonic chick skin may be attributed to a third mechanism, namely to an inhibition of the release
of proteolytic enzymes from lysosomes which is normally observed in
tissues exposed to u.v. irradiation. The retardation of the vitamin A
effect in bone and skin may be due to a similar mechanism, since
vitamin A has also been shown to induce a liberation of lysosomal
proteases.
615
containing hydrocortisone, the vitamin A effect was diminished in
both media, but to a greater degree in the medium containing hydrocortisone. The degree of recovery also varied with individual bones:
for instance, mouse radii and ulnae continued to disintegrate, while
the tibiae recovered partially.
Although cortisone and hydrocortisone show a similar effect on bone
growth in vivo and in vitro the retardation of the vitamin A effect by
hydrocortisone is strikingly different from that in vivo, where it is potentiated by the hormone (Selye, 1958). This is probably due to a release
of stored vitamin A from the liver under the influence of hydrocortisone
(Clark and Colburn, 1955). It is likely that the effect of the hormone
on cultures involves a different mechanism. Vitamin A releases an
acid protease from the chondrocytes which digests the matrix (Dingle,
1961) and it is possible that hydrocortisone inhibits the synthesis or
release of this enzyme. The same mechanism would also explain the
inhibition of the vitamin A effect on the epidermis.
3. Summary
The results show that corticosteroids directly affect various parameters of growth and differentiation and that in each instance different
mechanisms seem to be responsible. High doses severely damage or
inhibit the proliferation of cells—in particular, those derived from the
connective tissue including lymphocytes and melanophores—while
endothelium seems more resistant to the agent. This inhibition is
bound up with a reduction of respiration combined with a rise of
glycolysis in the treated cells. Low doses, on the other hand, increase
both respiration and cell proliferation. Intermediate concentrations
of the hormone which, when applied alone, were ineffective, increased
the growth-promoting effect of insulin on chick-heart fibroblasts, and
reversed the inhibition of growth seen after application of growth
hormone.
The retardation of growth observed in embryonic limb-bone
rudiments is not due to an inhibition of cell proliferation but to a
disturbance of cartilage formation, probably brought about by an
inhibition of chondroitin sulphate synthesis.
The mitigation of u.v. burns in embryonic chick skin may be attributed to a third mechanism, namely to an inhibition of the release
of proteolytic enzymes from lysosomes which is normally observed in
tissues exposed to u.v. irradiation. The retardation of the vitamin A
effect in bone and skin may be due to a similar mechanism, since
vitamin A has also been shown to induce a liberation of lysosomal
proteases.