A quantitative study of the physiologic action of thyroxin.

The isolation of thyroxin in pure crystalline form permitted the fact to be shown that thyroxin alone increases the rate of combustion in the animal organism. Furthermore, this increase is related quantitatively to the amount injected. One milligram given to an adult produces an increase of approximately 2.5 per cent. The substance acts in minute amounts for long periods, and produces such enormous increase in the output of carbon dioxid above the former level, that there is no escape from the conclusion that thyroxin acts as a catalyst.

Through a study of closely related compounds, which were synthetically prepared, the fact was demonstrated that thyroxin can exist in two forms: reduced and oxidized. Thyroxin, as isolated from the gland, is the reduced form.

Alpha oxy indol propionic acid, the precursor of thyroxin, acts as a reducing agent. It loses two atoms of hydrogen, with molecular oxygen, when the pyrrol ring in the molecule is open, and forms a bond from the nitrogen, to the number seven carbon in the benzene ring. This compound has feeble oxidizing power. When, however, the pyrrol ring is closed and the bond is present from the nitrogen to number seven carbon, the oxidizing power of the compound is very much increased. The oxidizing potentials of the open and the closed ring compounds, when both exist in their oxidizing form, have been measured, and a difference of at least 0.3 volt was found.

When they are injected into a normal dog, the reduced form, and the oxidized but open ring form, produce no visible response; the oxidized closed ring form causes a marked physiologic effect. There is a drop in blood pressure, an increase in pulse rate, a marked increase in respiration, and an increase in the rate of metabolism.