Activin Signaling through Activin Receptor Type II Causes the Cachexia-Like Symptoms in Inhibin-Deficient Mice

Katherine A. Coerver, Teresa K. Woodruff, Milton J. Finegold, Jennie Mather, Allan Bradley, Martin M. Matzuk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


Activins and inhibins, members of the transforming growth factor-β superfamily, are involved in diverse physiological and developmental processes. We have previously shown that mice deficient in α-inhibin develop gonadal sex cord-stromal tumors at an early age. The tumor development is rapidly followed by a wasting syndrome that includes severe weight loss, hepatocellular necrosis around the central vein, and depletion of the parietal cells in the glandular stomach. The liver histology in inhibin-deficient mice is similar to the pathological effects of short-term treatment of rats and mice with recombinant activin A. Consistent with these findings, we have shown that the gonadal tumors in the inhibin-deficient mice secrete high levels of activins. In addition, Northern blot analysis has localized activin receptor type II (ActRII) to the liver. Based on these studies, we postulated that tumor-produced activins act through ActRII to cause the wasting syndrome in inhibin-deficient mice. To test this hypothesis and determine the significance of elevated levels of activin signaling through ActRII in vivo, we generated compound homozygous mutant mice deficient in both α-inhibin and ActRII. Despite the continued development of gonadal sex cord-stromal tumors and elevated serum levels of activin A and B, the compound homozygous mutant mice suffered no unusual weight loss, and the stomachs and livers of the majority of the mice were histologically normal. These results demonstrate that increased levels of activin signaling through ActRII in hepatocytes and the glandular stomach causes the hepatocellular necrosis and depletion of parietal cells in the glandular stomach as well as the severe weight loss in vivo.

Original languageEnglish (US)
Pages (from-to)534-543
Number of pages10
JournalMolecular Endocrinology
Issue number5
StatePublished - 1996

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology


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