Effect of Single Treatment of Rats with Procarbazine on the Pituitary-Testicular Axis
Despite a few clinical reports suggesting dysfunction of the Hypothalamic-Pituitary-Testicular Axis (HPTA) following anticancer therapy, this area and particularly Leydig cell (LC) toxicity have not been explored in detail. To further study these aspects, groups of 5 or 4 male Fü-albino rats were treated once ip with 200 mg/kg of procarbazine (Proc) or the water vehicle respectively. 3, 7 and 14 days (d) later, blood was collected from the abdominal aorta for estimation of testosterone (T), LH (reference NIAMDD RP 2) and FSH (NIAMDD RP 1). Testes were fixed in 5% glutaraldehyde for investigation in electron microscopy (EM).
The mean concentration of hormones in Proc-treated animals in per cent of control values (C) were:
T/LH ratios were decreased (s at d3 and d3–d14 combined). Preliminary EM investigations revealed changes in chromatin distribution as well as some rarefaction and partly pronounced vacuolization of the smooth endoplasmic reticulum (SER) at d3–d14. Germ cell toxicity was relatively mild before d7. Thus, a single fairly well tolerated dose of Proc was followed by an early impairment of the HPTA, accompanied by morphologic signs of LC toxicity and relatively slow appearance of germ cell toxicity. The low T/LH ratio suggests that Proc may directly act on LC, in particular on structures related to cell regulation (nuclei) and T production (SER).
Key wordsTestis Leydig cells Male sex hormones Toxicity Procarbazine Natulan
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