TY - JOUR
T1 - Synergistic effects of inhibins and müllerian-inhibiting substance on testicular tumorigenesis
AU - Matzuk, Martin M.
AU - Finegold, Milton J.
AU - Mishina, Yuji
AU - Bradley, Allan
AU - Behringer, Richard R.
PY - 1995/10
Y1 - 1995/10
N2 - Members of the transforming growth factor-β (TGF-β) superfamily regulate diverse physiological processes in multiple tissues. In particular, important roles for the inhibins and Müllerian-inhibiting substance (MIS) have been demonstrated in the regulation of cell growth control both in vitro and in vivo. Inhibin-deficient male and female mice develop mixed granulosa/Sertoli cell tumors with nearly 100% penetrance. MIS-deficient male mice develop as pseudohermaphrodites with oviducts and uteri. In addition, MIS-deficient males have Leydig cell hyperplasia and, in one case, a Leydig cell tumor. To determine whether MIS could modify the development of the granulosa/Sertoli cell tumors in inhibin-deficient mice or whether inhibin could alter the development of the Leydig cell hyperplasia of MIS-deficient mice, animals deficient for both inhibins and MIS were generated. Adult inhibin/MIS-deficient male mice developed testicular tumors and large fluid-filled uteri. The accumulation of uterine fluid was due in part to an increase in estradiol secretion from the tumors and was blocked by a pure estrogen antagonist, ICI 182,780. The testes of the inhibin/MIS-deficient males developed granulosa/Sertoli cell tumors and Leydig cell neoplasia earlier, grew faster, were less hemorrhagic, and produced less estradiol than the testes of inhibin-deficient controls. These results demonstrate that inhibins and MIS synergize to influence testicular tumor development.
AB - Members of the transforming growth factor-β (TGF-β) superfamily regulate diverse physiological processes in multiple tissues. In particular, important roles for the inhibins and Müllerian-inhibiting substance (MIS) have been demonstrated in the regulation of cell growth control both in vitro and in vivo. Inhibin-deficient male and female mice develop mixed granulosa/Sertoli cell tumors with nearly 100% penetrance. MIS-deficient male mice develop as pseudohermaphrodites with oviducts and uteri. In addition, MIS-deficient males have Leydig cell hyperplasia and, in one case, a Leydig cell tumor. To determine whether MIS could modify the development of the granulosa/Sertoli cell tumors in inhibin-deficient mice or whether inhibin could alter the development of the Leydig cell hyperplasia of MIS-deficient mice, animals deficient for both inhibins and MIS were generated. Adult inhibin/MIS-deficient male mice developed testicular tumors and large fluid-filled uteri. The accumulation of uterine fluid was due in part to an increase in estradiol secretion from the tumors and was blocked by a pure estrogen antagonist, ICI 182,780. The testes of the inhibin/MIS-deficient males developed granulosa/Sertoli cell tumors and Leydig cell neoplasia earlier, grew faster, were less hemorrhagic, and produced less estradiol than the testes of inhibin-deficient controls. These results demonstrate that inhibins and MIS synergize to influence testicular tumor development.
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M3 - Article
C2 - 8544842
AN - SCOPUS:0029144102
SN - 0888-8809
VL - 9
SP - 1337
EP - 1345
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 10
ER -