Quantitative observations on thyroxine and allied substances

Abstract

IT was thought desirable to amplify by other methods the results obtained with tadpoles(1) in the study of the effects of natural and synthetic thyroxine and of various intermediate and related compounds prepared by Dr C. R. Harington. For this purpose it was decided to measure their action in increasing the gaseous metabolism of mammals.In the early investigations of the effects of thyroid preparations, an account of which will be found in Grafe's monograph(2), no attempt was made to obtain quantitative results. Thyroxine was first isolated by Kendall(3) in 1914, and was found to produce on injection all the known effects of thyroid preparations. This discovery was followed by various attempts to devise a reliable method of measuring thyroid activity. Plummer and Boothby(4) studied the effect of thyroxine on the basal metabolism of 69 cases of myxcedema and came to the conclusion that each milligramme of thyroxine would produce a maximal increase of 2X8 p.c. of the normal rate and that this maximuim occurred about 8 days after the injection. The "average variation" from this figure was only 25 p.c., and the relation appears to hold for all doses between 5 and 15 mg.Various German writers, using smaller doses, observed comparatively larger effects, after the injection of thyroxine, which developed and passed away in a couple of days (5).For many purposes, and in particular for the study of substances with unknown properties, it is desirable to make experiments with animals other than man. Unfortunately, the work that has been done in this direction has not hitherto given such clear results as those obtained by Plummer and Boothby.Meta Kunde (6) has published an account of a careful investigation of the effect of thyroid preparations on dogs. She comes to the conclusion 252

Oxygen consumption and body temperature in new‐born kittens subjected to hypoxia and reoxygenation

“…It is therefore possible to distinguish between periods of activity and rest and hence make an estimate of basal metabolic rate (B.M.R.). This was done wherever possible according to the following convention, which was used by Gaddum (1930). A total time of 20 min was assembled, usually of four periods of 5 min, picked out with dividers from those periods showing no disturbance of the record due to movement, and giving the lowest rates of oxygen consumption.…”

The Measurement of Oxygen Consumption in Small Animals

“…Six Perspex cylinders are set horizontally between two long sides, with the ends just short of the outer faces. These cylinders form the outer walls of the six metabolism chambers (1)(2)(3)(4)(5)(6) and are covered by circular Perspex plates 5 in. in diameter.…”

The Rates of Utilization of Thyroxine and of Desiccated Thyroid in Man: The Relation Between the Iodine in Desiccated Thyroid and in Thyroxine

“…Since, on the basis of equivalent iodine contents, the effect of this polypeptide was the same as that of Squibb's thyroxine (Salter, Lerman and Means (1932)), which is racemic (Kendall (1931)), it would seem that optical activity may be disregarded in the interpretation of our data. There remain the observations of Gaddum (1930) on four rats, which led him to the conclusion that 1-thyroxine is two and one-half times as effective as d-thyroxine. While we feel that his observations are inadequate to support such an important conclusion, our data, for purposes of completeness, may be considered in the light of his findings.…”

“…Gaddum (1930), using material supplied to him by Harington, concluded that levorotatory thyroxine had about two and one-half times as much effect on the oxygen consumption of a normal rat as the dextro-form. Harington and Salter (1930) showed that the levorotatory form, isolated by means of tryptic digestion, was the naturally occurring variety.…”

“…T.), Kendall did not think this hypothesis was justified, because of the finding by Harington and Randall (1929) of diiodotyrosine in the thyroid and their conclusion that the iodine in the gland is about equally divided between diiodotyrosine and thyroxine. Diiodotyrosine is said to have no effect on the oxygen consumption of normal rats (Gaddum (1930)), none on that of normal man (Hoffmann (1927)) and none in myxedematous individuals (Strouse and Voegtlin (1909), Thompson and Alper (1932)). …”