Development of Cancer Cachexia-Like Syndrome and Adrenal Tumors in Inhibin-Deficient Mice
Activins and inhibins, members of the type β transforming growth factor superfamily of growth regulatory proteins, are produced in multiple tissues and affect diverse physiologic processes. Using embryonic stem cell technology, we previously demonstrated that inhibin can function as a gonadal tumor...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 19; pp. 8817 - 8821 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences of the United States of America
13.09.1994
National Acad Sciences National Academy of Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Activins and inhibins, members of the type β transforming growth factor superfamily of growth regulatory proteins, are produced in multiple tissues and affect diverse physiologic processes. Using embryonic stem cell technology, we previously demonstrated that inhibin can function as a gonadal tumor suppressor. In this study, we show that development of gonadal tumors is rapidly followed by a cancer cachexia-like wasting syndrome. Cachectic inhibin-deficient mice develop hepatocellular necrosis around the central vein and parietal cell depletion and mucosal atrophy in the glandular stomach, are anemic, and demonstrate severe weight loss. The liver pathology is consistent with studies demonstrating an effect of elevated activins on rat hepatocytes. In inhibin-deficient mice with tumors, activins are >10-fold elevated in the serum and are likely causing some of the cachexia symptoms. In contrast, inhibin-deficient mice gonadectomized at an early age do not develop this wasting syndrome. However, these gonadectomized, inhibin-deficient mice eventually develop adrenal cortical sex steroidogenic tumors with nearly 100% penetrance, demonstrating that inhibin is also a tumor suppressor for the adrenal gland. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.91.19.8817 |