Relationship among hormonal treatments, suppression of spermatogenesis, and testicular protection from chemotherapy-induced damage.
To further elucidate the mechanism by which hormonal pretreatment protects the rat testis from damage by procarbazine, we investigated the relationship between the suppression of hormone levels and spermatogenesis and the recovery of spermatogenesis from stem spermatogonia. LBNF1 rats were implanted with capsules containing testosterone or testosterone plus estradiol. After hormone treatment, rats were injected with procarbazine, and recovery of spermatogenesis was assessed. Testosterone (2 cm) plus estradiol (0.5-cm) reduced serum LH levels causing intratesticular testosterone (ITT) to fall to 3% of control levels within 2 weeks, but testis weights and sperm head counts were not appreciably suppressed until 4 weeks. Two weeks' hormone pretreatment, only slightly enhanced spermatogenesis recovery, but 4 weeks markedly increased it. Testosterone (2 cm) alone produced slower suppression of spermatogenesis and less protection from procarbazine than did testosterone plus estradiol implants, despite equivalent suppression of LH and ITT. Long testosterone implants (24-cm) partially maintained ITT at 14% of control despite undetectable LH levels, prevented any decline in sperm counts, and nearly completely abrogated the protective effect of the hormone treatment. Protection appeared to be best correlated with the testis weight reduction by hormone treatment. Thus, recovery of spermatogenesis after chemotherapy is dependent on the degree of suppression of spermatogenesis caused by the reduction of ITT levels at the time of chemotherapy and likely involves cells, such as the Sertoli cells, that are both androgen-responsive and affected by the numbers of germ cells present.
Meistrich
M L
ML
Department of Experimental Radiotherapy, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Wilson
G
G
Ye
W S
WS
Thrash
C
C
Huhtaniemi
I
I
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology*; D008297:Male; D011344:Procarbazine / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000494:pharmacology*; D013997:Time Factors
D000970:Antineoplastic Agents; D004338:Drug Combinations; D011344:Procarbazine; D013739:Testosterone; D004958:Estradiol