Ceramide increases steroid hormone production in MA-10 Leydig cells

Christopher Kwun, Aneeta Patel, Sue Pletcher, Bridget Lyons, Maged Abdelrahim, Diarmuid Nicholson, Elena Morris, Kalman Salata, Gary L. Francis

Producción científica: Articlerevisión exhaustiva

17 Citas (Scopus)

Resumen

Ceramide is known to have major roles in the control of cell proliferation, differentiation, and apoptosis. Recent studies also have shown that ceramide affects steroid production by JEG-3 choriocarcinoma cells, acutely dispersed rat Leydig cells, and ovarian granulosa cells, but the mechanism by which this occurs is unknown. Because ceramide induces apoptosis in many different cell types, we hypothesized that ceramide might affect steroidogenesis and/or induce apoptosis in MA-10 murine Leydig cells. To test this, MA-10 cells were incubated with either the water soluble C2-ceramide, (N-acetyl-sphingosine, 0.01-10 cm); bacterial sphingomyelinase (1-100 mU/ml); or C2-dihydroceramide (N-acetyl-sphinganine, 0.1-10 μM). The data show that N-acetyl-sphingosine significantly increased basal (0.87 ± 0.2 vs. 0.42 ± 0.09 ng/mg cell protein, P < 0.01) and human chorionic gonadotropin (hCG) stimulated progesterone (P) synthesis (204 ± 12 vs. 120 ± 5 ng/mg cell protein, P < 0.001); as did sphingomyelinase (basal P = 0.83 ± 0.1 ng/mg cell protein, P < 0.01; hCG stimulated P = 173 ± 7 ng/mg cell protein, P < 0.001). C2-dihydroceramide also increased basal P synthesis but was less effective than ceramide on a molar basis. Neither sphingomyelinase (100 mU/ml) nor ceramide (10 μM) had any effect on cAMP production or human chorionic gonadotropin binding; and neither induced any signs of apoptosis (FragEL DNA fragmentation assay and electron microscopy). Cells incubated with anti-Fas (300 ng/ml) demonstrated DNA fragmentation, nuclear condensation, and frequent apoptotic bodies, but had no change in P synthesis. These data show that ceramide significantly increases MA-10 Leydig cell P synthesis but does not induce apoptosis. The mechanism by which ceramide increases steroid hormone synthesis remains unknown but does not appear to be linked to the induction of apoptosis in MA-10 cells. Copyright (C) 1999.

Idioma originalEnglish (US)
Páginas (desde-hasta)499-509
Número de páginas11
PublicaciónSteroids
Volumen64
N.º8
DOI
EstadoPublished - ago 1999
Publicado de forma externa

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Organic Chemistry

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