204
RACHMIEL LEVINE
These logically consistent and well-conceived experiments have
brought us undoubtedly nearer to the "action" of adrenaline, but have
not yet clearly defined it. Thus it is difficult to see why the effect of
adrenaline in reactivating the Phosphorylase system should invariably
lead to a breakdown of glycogen. Increased glycogen synthesis would
be an equally if not more likely result. Yet adrenaline administration
is always followed by glycogen breakdown, even in the presence of
added glucose.
^
Although adrenaline reactivates liver Phosphorylase and brings its
level back to the control values, there is at present no evidence that the
Phosphorylase is inactive under normal conditions. Since adrenaline
given in vivo or added to liver slices in vitro very quickly increases the
glucose output, the reactivation hypothesis does not seem to explain
the phenomenon completely, unless a major portion of the system is
normally in the inactive form.
It has been a controversial matter of long standing whether adrenaline
inhibits the uptake of glucose by muscle and other extrahepatic tissues
(see 5). If this is so, there is a possibility that inhibition of glucose
uptake would be secondary to an accumulation of glucose-6-phosphate,
which may inhibit the hexokinase reaction.
IV. THYROID HORMONES
Until recently it was assumed that the thyroid gland secreted a single
active substance, and the bulk of the evidence indicated that this was
thyroxine or tetraiodothyronine, which was transported in the blood
bound to the serum proteins. It was therefore assumed that the effects
of the thyroid secretion were all to be looked for in the effects of
thyroxine. The work of Gross, of Pitt-Rivers, of Thibault, and of Roche
now seems to indicate a need to broaden our viewpoint in several directions (Gross and Pitt-Rivers, 1952, 1953; Thibault, 1952; Thibault and
Pitt-Rivers, 1955; Roche and Michel, 1951, 1955). The epithelial cell
of the thyroid may secrete at least four active principles: (1) thyroxine;
(2) 3,3^5'-triiodotriyronine; (3) 3,5,3'-triiodothyronine; and (4) 3,3'diiodothyronine. Not only do these substances differ from each other
quantitatively, when tested for a particular biological effect, but there
seem to be some, as yet poorly known, qualitative differences between
their effects. In addition, the hormones may be chemically modified in
the tissues in several ways, to gain certain activities which they did not
possess in the unmodified form. It appears possible, although as yet unproven, that the acetic acid derivatives of thyroxine and triiodothyronine are the active stimulators of oxygen consumption, whereas the
RACHMIEL LEVINE
These logically consistent and well-conceived experiments have
brought us undoubtedly nearer to the "action" of adrenaline, but have
not yet clearly defined it. Thus it is difficult to see why the effect of
adrenaline in reactivating the Phosphorylase system should invariably
lead to a breakdown of glycogen. Increased glycogen synthesis would
be an equally if not more likely result. Yet adrenaline administration
is always followed by glycogen breakdown, even in the presence of
added glucose.
^
Although adrenaline reactivates liver Phosphorylase and brings its
level back to the control values, there is at present no evidence that the
Phosphorylase is inactive under normal conditions. Since adrenaline
given in vivo or added to liver slices in vitro very quickly increases the
glucose output, the reactivation hypothesis does not seem to explain
the phenomenon completely, unless a major portion of the system is
normally in the inactive form.
It has been a controversial matter of long standing whether adrenaline
inhibits the uptake of glucose by muscle and other extrahepatic tissues
(see 5). If this is so, there is a possibility that inhibition of glucose
uptake would be secondary to an accumulation of glucose-6-phosphate,
which may inhibit the hexokinase reaction.
IV. THYROID HORMONES
Until recently it was assumed that the thyroid gland secreted a single
active substance, and the bulk of the evidence indicated that this was
thyroxine or tetraiodothyronine, which was transported in the blood
bound to the serum proteins. It was therefore assumed that the effects
of the thyroid secretion were all to be looked for in the effects of
thyroxine. The work of Gross, of Pitt-Rivers, of Thibault, and of Roche
now seems to indicate a need to broaden our viewpoint in several directions (Gross and Pitt-Rivers, 1952, 1953; Thibault, 1952; Thibault and
Pitt-Rivers, 1955; Roche and Michel, 1951, 1955). The epithelial cell
of the thyroid may secrete at least four active principles: (1) thyroxine;
(2) 3,3^5'-triiodotriyronine; (3) 3,5,3'-triiodothyronine; and (4) 3,3'diiodothyronine. Not only do these substances differ from each other
quantitatively, when tested for a particular biological effect, but there
seem to be some, as yet poorly known, qualitative differences between
their effects. In addition, the hormones may be chemically modified in
the tissues in several ways, to gain certain activities which they did not
possess in the unmodified form. It appears possible, although as yet unproven, that the acetic acid derivatives of thyroxine and triiodothyronine are the active stimulators of oxygen consumption, whereas the