Suppression of mouse spermatogenesis by a gonadotropin-releasing hormone antagonist and antiandrogen: failure to protect against radiation-induced gonadal damage.
A combined GnRH antagonist (Nal-Glu) and antiandrogen (flutamide) treatment was used to suppress mouse spermatogenesis in an attempt to enhance recovery from stem cells after irradiation, as observed previously in the rat. Two weeks of treatment suppressed the intratesticular testosterone concentration to 10% of the control value, decreased testicular weight to 16% of the control value, and sperm count 2600-fold. Suppression was at least as great as that produced in the rat by Nal-Glu-flutamide. Testicular weights, sperm counts, and histology were indistinguishable from those in normal controls 45 days after the end of the treatment. Despite the suppression of spermatogenesis, the treatment did not enhance recovery of spermatogenesis after damage produced by a 10-Gray dose of radiation; 45 days after irradiation, testicular weight, sperm head counts, and repopulation indexes were as low as in the mice that received no hormone treatment. In contrast to the situation in the rat, after irradiation of mice, almost no A spermatogonia were found in the 80% non-repopulating tubules, indicating that nearly all A spermatogonia remaining after irradiation were capable of differentiation. This absence of A spermatogonia that fail to differentiate in the mouse is proposed as the reason for failure to protect against radiation-induced gonadal damage by hormone treatment.
Kangasniemi
M
M
Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Dodge
K
K
Pemberton
A E
AE
Huhtaniemi
I
I
Meistrich
M L
ML
D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D005485:Flutamide / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D013091:Spermatogenesis / Q000187:drug effects* / Q000528:radiation effects
D000726:Androgen Antagonists; C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D007987:Gonadotropin-Releasing Hormone; D005485:Flutamide