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 inProceedings of the National Academy of Sciences - PNAS Vol. 91; no. 19; pp. 8817 - 8821
Main Authors Matzuk, M. M., Finegold, M. J., Mather, J. P., Krummen, L., Lu, H., Bradley, A.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences of the United States of America 13.09.1994
National Acad Sciences
National Academy of Sciences
Subjects
Activins
Adrenal Gland Neoplasms - etiology
Animals
Cachexia
Cachexia - etiology
Cancer
Female
Hepatocytes
Histology
Inhibins - deficiency
Inhibins - metabolism
Liver
Male
Medical research
Mice
Mice, Knockout
Neoplasms, Gonadal Tissue - etiology
Orchiectomy
Ovariectomy
Proteins
Receptors
Rodents
Stomach
Tumors
Wasting syndrome
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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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ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.19.8817