The Metabolic Effects of Human Thyroglobulin and Its Proteolytic Cleavage Products.

In previous communications, (1, 2, 3, 4, 5) it has been pointed out that two important questions with regard to the nature of thyroid colloid must be answered because they bear upon the normal and pathological physiology of the gland. The first of these is: Does the colloid of " toxic " glands show significant differences from normal or " non-toxic " colloid? The second question is: Does the activity of the thyroid secretion depend solely upon its thyroxin content? This paper includes both chemical analyses and biological assays so correlated as to bring out possible causal relationships to the metabolic effects produced. As explained elsewhere, (1) a routine standard procedure was adopted for administering thyroid material to patients with myxedema. The magnitude of the metabolic response could then be used as a gauge of the potency of the preparation or drug administered. The thyroglobulins were prepared by extraction of freshly iced, surgically excised glands with 0.02 normal sodium hydroxide solution. The protein was subsequently precipitated isoelectrically; and then redissolved and reprecipitated repeatedly. The preparation of the di-iodotyrosine peptone and thyroxin peptone digests was accomplished as described by Harington and Salter (6). Undigested protein was eliminated by heat coagulation and by the acetone treatment described by these authors. Total iodine was estimated according to the procedure of Kendall (7). The thyroxin moiety was estimated by the procedure of Harington and Randall (8) and checked by the methods of Leland and Foster (9) or of Blau (10). The response of patients to test fractions of thyroid material was judged by comparison with the standard curve of reference obtained by administering natural thyroxin polypeptide (1). When this substance was fed in solution in daily doses containing 0.5 mgm. iodine, the daily rise in basal metabolic rate was found to average about 2.5 points (1). By this method the response of myxedematous patients could be calibrated when test preparations were administered. The reliability of this procedure has been discussed in a previous communication (5). A patient was never used for more than one assay, unless the first result was completely negative.