Protection from radiation-induced damage to spermatogenesis by hormone treatment.
Infertility caused by killing of the spermatogonial stem cells occurs frequently in men treated for cancer with radiotherapy and chemotherapy. We investigated whether pretreatment of rats with testosterone plus estradiol, which reversibly inhibits the completion of spermatogenesis and protects spermatogonial stem cells from procarbazine-induced damage, would also protect these cells from radiation. Adult male LBNF1 rats were implanted for 6 weeks with capsules containing testosterone and estradiol and then irradiated with doses from 2.5-7.0 Gy. Controls were irradiated with 1.8-3.5 Gy. Implants were removed 1 day after irradiation, and all animals were killed 10 weeks later for assessment of stem cell survival by counting repopulating tubules in histological sections and by sperm head counts. At doses of 2.5 and 3.5 Gy the repopulation indices and sperm head counts were significantly higher (P < 0.001) in the rats treated with testosterone and estradiol than in the controls. Protection factors (dose-modifying factors) calculated from the dose-response curves were in the range of 1.5-2.2. Elucidation of the mechanism of protection is essential to apply it to clinical situations. The fact that the spermatogonia are protected against radiation as well as procarbazine indicates that the mechanism does not involve drug delivery or metabolism.
Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
B
B
Kurdoglu
G
G
Wilson
N
N
Parchuri
W S
WS
Ye
M L
ML
Meistrich
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011344:Procarbazine / Q000633:toxicity; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013091:Spermatogenesis / Q000187:drug effects / Q000528:radiation effects*; D013093:Spermatogonia / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology*
D004343:Drug Implants; D011837:Radiation-Protective Agents; D011344:Procarbazine; D013739:Testosterone; D004958:Estradiol