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EFFECT OF CADMIUM AND OTHER METAL CATIONS ON IN VITRO LEYDIG CELL TESTOSTERONE PRODUCTION
Citation:
Laskey, J. AND P. Phelps. EFFECT OF CADMIUM AND OTHER METAL CATIONS ON IN VITRO LEYDIG CELL TESTOSTERONE PRODUCTION. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/092 (NTIS PB91200261).
Description:
In vivo assessment of toxicant action on Leydig cell function is subject to homeostatic mechanisms which make it difficult to determine whether any changes seen in serum testosterone (T) concentration are due to extragonadal endocrine alternations or to a direct effect on the Leydig cell. or example metal cations administered in vivo have been shown to depress serum testosterone concentration in addition to alterations in serum concentrations of pituitary hormones in laboratory animals (Cooper et al., 1987). he studies reported here use a testicular cell culture technique to evaluate Leydig cell testosterone biosynthesis in the presence of several metal cations. o determine the site of toxic action, the Leydig cells were stimulated to produce testosterone by using human chorionic gonadotrophin (hCG), dibutyl cyclic adenosine monophosphate (db cAMP) or several substrates required for the biosynthesis of testosterone. CG was chosen because resultant testosterone production requires an intact membrane receptor and db cAMP was used to test for post LH receptor defects caused by the metals. he other substrates were chosen to isolate the effect of metals on specific enzyme rates. ollagenase dispersed testicular cells (15% Leydig cells) were incubated with metal cations (1 to 5000 uM) for three hours in the absence and presence of maximally stimulating concentrations of either hCG, db cAMP, 200-hydroxycholesterol (HCHOL) or pregnenolone (PREG) and testosterone concentration was determined by radioimmunoassay. n one separate experiment we also tested the effect of the substrates progesterone. 70-hydroxy-progesterone and androstenedione on Cd++ treated Leydig cells. he results show no change in Leydig cell viability with any metal cation treatment during the three hour incubation. a++, CR+++, FE+++, Mg++, Na+ or PB++ had no effect on stimulated testosterone. ose response depression in both hCG and db-cAMP stimulated testosterone production were seen with CD++, CO++, Cu++, Hg++, Ni++, and Zn++ treatment. urprisingly several of the metal cations which caused a depression in hCG and db cAMP stimulated testosterone production caused significant increases in HCHOL and PREG stimulated testosterone production over untreated and similarly stimulated cultures.