Thirty mature and peripubertal male rabbits were examined for endocrine function and tissue methotrexate (MTX) concentration after single (57.5 mg/kgBW, group 1) and repeated (6 mg/kgBW, once a week for 14 weeks, group 2) MTX doses. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and androstenedione plasma levels were measured by radioimmunoassay (RIA). We found elevated plasma FSH levels in both groups. Elevated plasma androstenedione level and reduced plasma testosterone level in group 2 suggest an enzymatic defect in the gonadal steroid synthesis. Unchanged LH plasma level, when compared to controls, is thought to be the result of a combined effect of MTX on the gonadal steroids and gonadotropin synthesis.
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