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Endocrinology, doi:10.1210/endo-113-3-1072
Endocrinology Vol. 113, No. 3 1072-1076
Copyright © 1983 by the Endocrine Society.
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Organ-Specific Binding of a Thyrotropin-Releasing Hormone-Diphtheria Toxin Complex after Intravenous Administration to Rats*

P. BACHA, J. R. MURPHY and S. REICHLIN

Endocrine Division, New England Medical Center Boston, Massachusetts 02111
The Department of Microbiology and Molecular Genetics, Harvard Medical School Boston, Massachusetts 02115

Address requests for reprints to: Dr. Patricia Bacha, Endocrinology Division, Department of Medicine, Box 268,275; 171 Harrison Avenue, New England Medical Center, Inc., Boston, Massachusetts 02111.

Abstract

We have previously demonstrated that a hybrid protein consisting of TRH linked to CRM45, a fragment of diphtheria toxin which lacks its native cell-binding moiety, specifically binds to TRH receptors in vitro. In this study we have examined its iin vivo binding and shown that after iv injection, this complex labeled with 128I is selectively concentrated in the normal anterior pituitary and that concomitant administration of cold TRH reduces its uptake. Displaceable uptake was also demonstrated in the hypothalamus and testis, whereas nondisplaceable binding exceeding that of CRM45 alone was shown in the ovary and the breast parenchyma of lactating rats. Similar experiments with tritiated TRH were performed. We found that although there was uptake of the material by many tissues, almost all of the radioactivity was in the form of TRH degradation products. Therefore, we conclude that TRH linked to a large carrier like CRM45 may be a more revealing indicator of in vivo binding affinities than native TRH. (Endocrinology 113: 1072,1983)

Footnotes

* This work was supported by grants from the American Cancer Society (BC-377) and the NIH (AM-16684).

Received February 24, 1983.




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Copyright © 1983 by The Endocrine Society