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IN VITRO/IN VIVO EFFECTS OF ETHANE DIMETHANESULPHONATE ON LEYDIG CELLS OF ADULT RATS
Citation:
Klinefelter, G., J. Laskey, AND N. Roberts. IN VITRO/IN VIVO EFFECTS OF ETHANE DIMETHANESULPHONATE ON LEYDIG CELLS OF ADULT RATS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/049.
Description:
Ethane dimethanesulphonate (EDS) is studied extensively to date, certain toxicological criteria have not been met. or instance, the does-responsiveness of Leydig cells to EDS, both in vitro and in vivo, is not well established. n addition, the date regarding the cellular site of action of EDS during Leydig cell toxicity and the status of Leydig cell viability during the affected period remains controversial. e used both highly purified (98%) and interstitial (14%) Leydig cell preparations to determine the in vitro EC50 (370 uM) and in vivo ED50 (60 mg.kg) for hCG-stimulated testosterone (T) production, respectively. eydig cells were recovered in approximately equal numbers following all in vivo and in vitro EDS exposures. he Leydig cells in these preparations were viable and steroidogenically active (3B-HSD positive) subsequent to all exposures, both before and after incubations to stimulate T biosynthesis. hen hGG-stimulated T production was decreased 50% following in vivo or in vitro exposures, the morphological integrity of the Leydig cells appeared normal, with no discernible lesion at either light or electron microscope level. e used stimulants of various reactions in the pathway of T biosynthesis (20a-hydroxycholesterol and pregnenolone) to determine the site of action impaired when T biosynthesis was decreased 50% following in vivo or in vitro exposures. ur results indicate that when Leydig cells are exposed to EDS either in vitro or in vivo, the biosynthesis of T is compromised between the production of cyclic adenosine monophosphate (cAMP) activation of protein kinase and the cholesterol side chain cleavage enzyme.