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Effect of Single Treatment of Rats with Procarbazine on the Pituitary-Testicular Axis

  • R. A. Ettlin
  • F. Hadžiselimović
  • U. Hennes
Conference paper
Part of the Archives of Toxicology book series (TOXICOLOGY, volume 8)

Abstract

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 words

Testis Leydig cells Male sex hormones Toxicity Procarbazine Natulan 

References

  1. Ettlin RA, Bechter R, Dixon RL (1982) Assessment of testicular toxicity associated with anticancer agents. 1. Histopathology. Proc West Pharmacol Soc 25: 381–384Google Scholar
  2. Hadiiselimovie F, Seguchi H (1975) An electron microscopic study on the postnatal development of human Leydig cells. Proc 10th Int Congr Anat (Tokyo): 445Google Scholar
  3. Heywood LH (1980) Testosterone levels in the male laboratory rat: Variations under experimental conditions. Int J Androl 3: 519–529PubMedCrossRefGoogle Scholar
  4. Payne AH, O’Shaughnessy PJ, Chase DJ, Dixon GEK, Christensen AK (1982) LH receptors and steroidogenesis in distinct populations of Leydig cells. Ann NY Acad Sci 383: 174–203PubMedCrossRefGoogle Scholar
  5. Senge Th, Schenk B, Tunn U, Hülshoff Th, Neumann F (1978) A study of the capacity for regeneration of rat and human Leydig cells. Urol Res 6: 167–171PubMedCrossRefGoogle Scholar
  6. Wang C, Ng RP, Chan TK, Tood D (1980) Effect of combination chemotherapy on pituitary-gonadal function in patients with lymphoma and leukemia. Cancer 45: 2030–2037PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • R. A. Ettlin
    • 1
  • F. Hadžiselimović
    • 2
  • U. Hennes
    • 1
  1. 1.F. Hoffmann-La Roche & Co. Ltd.BaselSwitzerland
  2. 2.Pediatric DepartmentUniversity Children’s HospitalBaselSwitzerland

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