MECHANISM OF ACTION OF TRYPAN BLUE IN SUPPRESSING THYROID FUNCTION1

Abstract

Several of the possible pathways by which trypan blue may affect thyroid function were investigated. The abnormal serum globulin produced by trypan blue injection did not seem to inhibit thyroid activity directly since its appearance did not always coincide precisely temporally with decreased thyroid activity. Direct intrapituitary injection of 0.4 mg. of this protein prepared by continuous flow paper electrophoresis had no effect on thyroidal secretion. Direct injection of systemically ineffective amounts of trypan blue into the pituitary inhibited thyroid function. The intrahypophyseal injection of small amounts of Evans’ blue also suppressed thyroid function. The binding pattern of labeled thyroxine to the serum proteins of trypan blue-treated animals was quite different from that of normal controls. The amount of thyroxine bound to albumin decreased to 40% of the normal while the thyroxine bound to the protein between α-1 and α-2 globulin, where the abnormal serum protein is located, increased correspondingly. The shift in thyroxine binding seemed to be primarily between the albumin and interalpha globulin areas since there was no significant change in the amount of thyroxine bound to the other serum components. The hypophysis appeared to play an essential role in the appearance of the abnormal serum globulin following trypan blue administration. This globulin would appear when only l/100th of the minimal systematically effective dose of trypan blue was injected directly in the pituitary. Conversely, the protein did not appear when systemic doses of trypan blue which were effective in the control animals were given to hypophysectomized rats.