Possible involvement of ceramide in the regulation of rat Leydig cell function
| Autor: | Daniela F. Cánepa, Selva B. Cigorraga, Silvina Beatriz Meroni, Eliana Herminia Pellizzari |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty Ceramide Endocrinology Diabetes and Metabolism Clinical Biochemistry In Vitro Techniques Biology Sphingomyelin phosphodiesterase Ceramides Chorionic Gonadotropin Biochemistry Amidohydrolases Rats Sprague-Dawley chemistry.chemical_compound Endocrinology Internal medicine Ceramidases Cyclic AMP medicine Animals Testosterone Molecular Biology Leydig cell Tumor Necrosis Factor-alpha 17-alpha-Hydroxyprogesterone Androstenedione Leydig Cells Cell Biology Sphingolipid Rats Cholesterol medicine.anatomical_structure Bucladesine chemistry Ceramidase activity Pregnenolone Molecular Medicine Sphingomyelin Intracellular Interleukin-1 Signal Transduction medicine.drug |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 75:307-313 |
| ISSN: | 0960-0760 |
| DOI: | 10.1016/s0960-0760(00)00188-6 |
| Popis: | In the present study, a possible role of a ceramide-dependent pathway in the regulation of Leydig cell function was investigated. Intracellular ceramide levels were increased by: (a) adding ceramide analogs; (b) inhibiting ceramidase activity; and (c) adding sphingomyelinase (SMase). The cell-permeable ceramide analogs N -acetyl-, N -hexanoyl- and N -octanoylsphingosine (C2, C6 and C8) were used. As inhibitor of ceramidase activity 1 S ,2 R - d -erythro-2-( N -myristoylamino)-1-phenyl-1-propanol (MAPP) was used. Shingomyelinase from S. aureus origin was utilized. Leydig cells were cultured for 3 or 24 h with or without the different drugs (10 μM) and SMase (0.3 U/ml) in the presence or absence of hCG (10 ng/ml). Basal testosterone production was not modified under any of the experimental conditions. A decrease in hCG-stimulated testosterone production was observed at 3 and 24 h in all cases. The inactive analog ( N -hexanoyl dihydrosphingosine) did not produce inhibition in hCG-stimulated testosterone production. TNFα and IL1β, two possible inducers of sphingomyelin hydrolysis, produced similar effects on hCG-stimulated testosterone production. In experiments performed in the presence of C6, inhibition in hCG-stimulated cAMP production was observed. The inhibitory effect of ceramide was also observed in dbcAMP-stimulated cultures indicating that this pathway inhibits post-cAMP formation events. To study possible loci for the action of ceramide on the steroidogenic pathway, cells were incubated with C6 and MAPP in the presence of different testosterone precursors. The drugs inhibited testosterone produced from 22( R )-hydroxycholesterol (22 R- OHChol), pregnenolone and 17α-hydroxyprogesterone (17OHP4) but not from androstenedione (Δ4). These results suggest that a ceramide-dependent pathway regulates hCG-stimulated Leydig cell steroidogenesis at the level of cAMP production and at post-cAMP events. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect