RELATIONSHIP AMONG HORMONAL TREATMENTS, SUPPRESSION OF SPERMATOGENESIS, AND TESTICULAR PROTECTION FROM CHEMOTHERAPY-INDUCED DAMAGE

To further elucidate the mechanism by which hormonal pretreatment prot ects the rat testis from damage by procarbazine, we investigated the r elationship between the suppression of hormone levels and spermatogene sis and the recovery of spermatogenesis from stem spermatogonia. LBNF( 1) rats were implanted with capsules containing testosterone or testos terone plus estradiol. After hormone treatment, rats were injected wit h procarbazine, and recovery of spermatogenesis was assessed. Testoste rone (2 cm) plus estradiol (0.5-cm) reduced serum LH levels causing in tratesticular testosterone (ITT) to fall to 3% of control levels withi n 2 weeks, but testis weights and sperm head counts were not appreciab ly suppressed until 4 weeks. Two weeks' hormone pretreatment, only sli ghtly enhanced spermatogenesis recovery, but 4 weeks markedly increase d it. Testosterone (2 cm) alone produced slower suppression of spermat ogenesis and less protection from procarbazine than did testosterone p lus 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 sperma togenesis 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.