Studies on methotrexate effects on testicular steroidogenesis in rats

The effects of single dose, 4 consecutive days, 4 and 8 weekly doses of methotrexate (MTX) treatment (3 mg/kg body weight, intramuscularly) with and without leucovorin (LCN) supplementation (0.3 mg/kg body weight, intramuscularly) on serum testosterone titres, total, free and esterified cholesterol concentrations and steroidogenic enzymes, viz. 3beta- and 17beta-hydroxy steroid dehydrogenase activities were studied in adult albino rats. MTX treatment caused a marked reduction in serum testosterone titres in all the treatment groups in a duration-dependent manner. LCN supplementation did not restore serum testosterone titres to normalcy. Total and free cholesterol concentrations remained unaltered in both MTX and MTX + LCN treated groups. On the other hand, a marked increase in esterified cholesterol concentration was evident only in weekly dose treatment groups. The specific activities of 3beta- and 17beta-hydroxy steroid dehydrogenase were markedly diminished in both MTX and MTX + LCN treated groups. The results suggest the inhibitory effect of MTX on steroidogenesis.