644
I L S E
L A S N I T Z K I
Markert (1948) investigated the effects of thyroxine and antithyroid
drugs on pigment formation in vitro in skin explants from 7-day Barred
Plymouth Rock chick embryos. After 48 h incubation numerous melanoblasts were visible in nearly all cultures, and pigment formation, as
indicated by the number and darkness of the granules, continued up to
72 h and then ceased gradually. There was a general antagonism between the rate of growth ofthe skin fragments and pigment development.
Melanogenesis proceeded more rapidly in cultures kept in plasma
alone, where the growth was slow, than in plasma and extract where
it was more extensive.
Thyroxine added in concentrations ranging from 10~~
7 to 10~
4
M had
no influence on the number of melanophores or on their pigment
formation. It seems therefore that the hormone added to the medium
does not affect melanogenesis directly at this stage but that it achieves
its effect in adult chickens through the mediation of a metabolic
system which is not present in embryonic skin.
O n the other hand, several members of the thiourea group such as
phenylthiourea, a-naphthylthiourea, propylthiouracil and thiouracil
directly inhibited pigment formation in the skin explants. The duration
of the inhibition was proportional to the concentration of the drug and
could be shortened by transferring the treated cultures to a fresh
medium. Addition of thyroxine to the inhibitor did not reverse the
inhibition nor did that of tyrosine or cysteine which are normally
involved in pigment synthesis. The activity of the most potent inhibitors
a-naphthylthiourea and phenylthiourea was destroyed by iodine in
the medium, an effect which is probably due to the oxidation of the
drugs to an inactive compound. The inhibition of pigment formation
was also prevented by addition of appropriate concentrations of 3-4dihydroxyphenylalanine (Dopa) in a ratio of 10M of Dopa to 1M of
phenylthiourea.
Melanin is synthesized by a series of oxidations and Markert considered it probable that the inhibitors prevent this step by a reduction
of the precursors. The precise point at which these compounds act is
not known, but there is evidence that small doses prevent the oxidation of hallochrome while large doses affect pigment synthesis at an
earlier stage. The reversal of the inhibition of Dopa which is a melanin
precursor can be attributed to the fact that it increases the amounts
of substrate over that inactivated by the antithyroid drugs.
Thus, thyroxine, with the exception of melanophore formation in
embryonic chick skin, directly affects proliferation of unorganized cells
and the differentiation of bone rudiments in vitro. In cell cultures the
hormone promotes cell multiplication at low doses and inhibits it at
high concentrations independently of the species from which the cells
I L S E
L A S N I T Z K I
Markert (1948) investigated the effects of thyroxine and antithyroid
drugs on pigment formation in vitro in skin explants from 7-day Barred
Plymouth Rock chick embryos. After 48 h incubation numerous melanoblasts were visible in nearly all cultures, and pigment formation, as
indicated by the number and darkness of the granules, continued up to
72 h and then ceased gradually. There was a general antagonism between the rate of growth ofthe skin fragments and pigment development.
Melanogenesis proceeded more rapidly in cultures kept in plasma
alone, where the growth was slow, than in plasma and extract where
it was more extensive.
Thyroxine added in concentrations ranging from 10~~
7 to 10~
4
M had
no influence on the number of melanophores or on their pigment
formation. It seems therefore that the hormone added to the medium
does not affect melanogenesis directly at this stage but that it achieves
its effect in adult chickens through the mediation of a metabolic
system which is not present in embryonic skin.
O n the other hand, several members of the thiourea group such as
phenylthiourea, a-naphthylthiourea, propylthiouracil and thiouracil
directly inhibited pigment formation in the skin explants. The duration
of the inhibition was proportional to the concentration of the drug and
could be shortened by transferring the treated cultures to a fresh
medium. Addition of thyroxine to the inhibitor did not reverse the
inhibition nor did that of tyrosine or cysteine which are normally
involved in pigment synthesis. The activity of the most potent inhibitors
a-naphthylthiourea and phenylthiourea was destroyed by iodine in
the medium, an effect which is probably due to the oxidation of the
drugs to an inactive compound. The inhibition of pigment formation
was also prevented by addition of appropriate concentrations of 3-4dihydroxyphenylalanine (Dopa) in a ratio of 10M of Dopa to 1M of
phenylthiourea.
Melanin is synthesized by a series of oxidations and Markert considered it probable that the inhibitors prevent this step by a reduction
of the precursors. The precise point at which these compounds act is
not known, but there is evidence that small doses prevent the oxidation of hallochrome while large doses affect pigment synthesis at an
earlier stage. The reversal of the inhibition of Dopa which is a melanin
precursor can be attributed to the fact that it increases the amounts
of substrate over that inactivated by the antithyroid drugs.
Thus, thyroxine, with the exception of melanophore formation in
embryonic chick skin, directly affects proliferation of unorganized cells
and the differentiation of bone rudiments in vitro. In cell cultures the
hormone promotes cell multiplication at low doses and inhibits it at
high concentrations independently of the species from which the cells