In vitro effects of ethylene-dimethane sulfonate (EDS) on Leydig cells: inhibition of steroid production and cytotoxic effects are dependent on species and age of rat.
A number of proteins in Leydig cells isolated from immature rats, mature rats and tumour tissue as well as protein in Sertoli cells, hepatocytes and blood plasma are alkylated after incubation of cells with 14C-labelled ethylene-dimethane sulfonate (EDS) for 5 h. LH-stimulated and 22R-hydroxycholesterol-supported steroid production by Leydig cells from immature and mature rats and from rat tumour tissue but not from testes of mature mice was strongly or completely inhibited after incubation with EDS. EDS had no effects on ATP levels in Leydig cells from mature rats after an incubation period of 24 h but ATP levels were almost zero after 72 h. In Leydig cells from tumour tissue the ATP level was decreased to 10% of the original value after 24 h EDS and decreased further during the following 48 h period. In Leydig cells from immature rats EDS had no effect on ATP levels after 72 h incubation. Ultrastructural evidence of cell damage by EDS was observed in cells from mature rats and tumour tissue but not in cells from immature rats. Discrepancies between biochemical and morphological indications for cell damage were noticed after 24 h incubation with EDS but not after 72 h. The results show that EDS exerts a direct inhibitory effect on both mature and immature rat Leydig cells but does not affect LH-stimulated steroid production by mouse Leydig cells. A cytotoxic response to EDS develops in rat Leydig cells during maturation. However, the molecular basis for these very specific effects of EDS on Leydig cells is at present not understood.
Rommerts
F F
FF
Department of Biochemistry, Chemical Endocrinology, Erasmus UniversityRotterdam, The Netherlands.
Teerds
K J
KJ
Hoogerbrugge
J W
JW
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging; D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D006888:Hydroxycholesterols / Q000494:pharmacology; D007984:Leydig Cell Tumor / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008099:Liver / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D008698:Mesylates / Q000633:toxicity*; D051379:Mice; D011284:Pregnenolone / Q000096:biosynthesis*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D012708:Sertoli Cells / Q000378:metabolism; D012741:Sexual Maturation; D013045:Species Specificity; D013736:Testicular Neoplasms / Q000378:metabolism; D013737:Testis / Q000254:growth & development*
D000477:Alkylating Agents; D006888:Hydroxycholesterols; D008698:Mesylates; D011506:Proteins; C003585:22-hydroxycholesterol; D011284:Pregnenolone; D000255:Adenosine Triphosphate; D007986:Luteinizing Hormone; C002994:ethylene dimethanesulfonate