Effects of ethane dimethanesulfonate (EDS) on adult and immature rabbit Leydig cells: comparison with EDS-treated rat Leydig cells.
Ethane-dimethanesulfonate (EDS) has been shown to selectively kill Leydig cells and depress testosterone production in adult rats. A recent study has shown that immature rat Leydig cells are less sensitive to EDS exposure. There is evidence that the rabbit metabolizes EDS to methane sulfonic acid more rapidly than does the rat, reducing exposure to the parent compound. In the study reported here, we examined the effects of EDS on the Leydig cells in both adult and immature rabbits and compared the effects found with those previously reported in the rat. In vivo, EDS exposure demonstrated that Leydig cells from adult rabbits were affected, with both serum and interstitial testosterone production depressed. EDS effects in adult rabbits and rats were compared by exposing explants of testicular parenchyma to EDS in vitro and evaluating testosterone production. With this procedure, the rabbit testis was less sensitive to EDS treatment than the rat, with a 50% reduction rate (EC50) achieved with 2026 microM EDS for the rabbit and with 336 microM EDS for the rat. Perfusion of adult and immature rabbit testis with 430 microM EDS demonstrated the insensitivity of the immature testis to EDS exposure: adult testosterone production was reduced 50% in 3.5 h, whereas no diminution was found in the immature rabbit. EDS exposure of interstitial cell preparations further demonstrated the insensitivity of immature rabbit Leydig cells, with an EC50 of 4397 microM compared to an EC50 of 1137 microM EDS in adult preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
Reproductive Toxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
J W
JW
Laskey
G R
GR
Klinefelter
W R
WR
Kelce
L L
LL
Ewing
D000375:Aging; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D046508:Culture Techniques; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008698:Mesylates / Q000008:administration & dosage / Q000494:pharmacology*; D008854:Microscopy, Electron; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects / Q000254:growth & development*; D013739:Testosterone / Q000096:biosynthesis
D006063:Chorionic Gonadotropin; D008698:Mesylates; D013739:Testosterone; D003994:Bucladesine; C002994:ethylene dimethanesulfonate