Inhibitory effects of TNF alpha on mouse tumor Leydig cells: possible role of ceramide in the mechanism of action.
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Inhibitory effects of TNF alpha on mouse tumor Leydig cells: possible role of ceramide in the mechanism of action. / Budnik, Lygia Therese; Jähner, D; Mukhopadhyay, A K.
In: MOL CELL ENDOCRINOL, Vol. 150, No. 1-2, 1-2, 1999, p. 39-46.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Inhibitory effects of TNF alpha on mouse tumor Leydig cells: possible role of ceramide in the mechanism of action.
AU - Budnik, Lygia Therese
AU - Jähner, D
AU - Mukhopadhyay, A K
PY - 1999
Y1 - 1999
N2 - TNF alpha is reported to inhibit steroidogenesis in mouse Leydig cells. In primary cells this inhibition resulted mainly from a reduced expression of Cyp-17 gene. Mouse tumor Leydig cells, MA-10, being free of macrophages and lacking Cyp-17, appear to be an excellent model to investigate those effects of TNF alpha which are independent of either macrophages or Cyp-17. We report here that TNF alpha receptors are expressed in this cell line. Treatment of the cells with TNF alpha had no effect on basal progesterone production. In contrast, LH-, 8Br-cAMP and forskolin-stimulated progesterone production was inhibited by TNF alpha. Neither enzymes involved in the conversion of cholesterol to pregnenolone nor hormone-induced hydrolysis of [14C] cholesterol-ester were affected by TNF alpha. The hormone-induced expression of StAR protein was diminished in mitochondrial fractions from TNF alpha-treated cells. Also cell permeable ceramides markedly inhibited StAR protein levels. We show further that TNF alpha was able to induce [14C]-ceramide accumulation in MA-10 cells and suggest that this sphingolipid may be considered as a transmitter of TNF alpha signals to the StAR protein.
AB - TNF alpha is reported to inhibit steroidogenesis in mouse Leydig cells. In primary cells this inhibition resulted mainly from a reduced expression of Cyp-17 gene. Mouse tumor Leydig cells, MA-10, being free of macrophages and lacking Cyp-17, appear to be an excellent model to investigate those effects of TNF alpha which are independent of either macrophages or Cyp-17. We report here that TNF alpha receptors are expressed in this cell line. Treatment of the cells with TNF alpha had no effect on basal progesterone production. In contrast, LH-, 8Br-cAMP and forskolin-stimulated progesterone production was inhibited by TNF alpha. Neither enzymes involved in the conversion of cholesterol to pregnenolone nor hormone-induced hydrolysis of [14C] cholesterol-ester were affected by TNF alpha. The hormone-induced expression of StAR protein was diminished in mitochondrial fractions from TNF alpha-treated cells. Also cell permeable ceramides markedly inhibited StAR protein levels. We show further that TNF alpha was able to induce [14C]-ceramide accumulation in MA-10 cells and suggest that this sphingolipid may be considered as a transmitter of TNF alpha signals to the StAR protein.
M3 - SCORING: Zeitschriftenaufsatz
VL - 150
SP - 39
EP - 46
JO - MOL CELL ENDOCRINOL
JF - MOL CELL ENDOCRINOL
SN - 0303-7207
IS - 1-2
M1 - 1-2
ER -
