Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats.

Possible protective effects of the agonist [D-Trp6]LH-RH (analog of luteinizing hormone-releasing hormone in which Gly-6 is replaced by D-tryptophan) and antagonist N-Ac-[D-Phe(pCI)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH against testicular damage caused by x-radiation were investigated in rats. Three months after being subjected to x-irradiation of the testes with 415 or 622 rads, control rats showed marked reduction in the weights of the testes and elevated levels of LH and follicle-stimulating hormone (FSH), indicating tubular damage. Histological studies demonstrated that, in testes of rats given 415 rads, most seminiferous tubules had only Sertoli cells and no germinal cells, and, in the group given 622 rads, the depression of spermatogenesis was even more marked. Rats pretreated for 50 days with LH-RH antagonist (1000 micrograms/kg of body weight per day) showed a complete recovery of testicular weights and spermatogenesis 3 months after 415 rads and showed partial recovery after 622 rads, and LH and FSH levels returned to normal in both of these groups. Thus, pretreatment of rats with LH-RH antagonist, by reversibly inhibiting gonadal function, protected the germinal cells of the testes against damaging effects of x-rays. Three experiments were also carried out in which the rats were pretreated for 1-2 months with long-acting microcapsules of the agonist [D-Trp6]LH-RH, liberating 25 micrograms of the agonist per day. Some rats were then subjected to gonadal irradiation with 415 or 622 rads and allowed a recovery period of 2-4 months. In spite of pretreatment with [D-Trp6]LH-RH, testicular weights were significantly lower and LH or FSH levels were elevated in the irradiated groups as compared with nonirradiated controls. The recovery of spermatogenesis was incomplete, and there was a decrease in the number of germinal cells after 415 rads and especially after 622 rads. On the basis of testicular weights, histology, and gonadotropin levels, it could be concluded that the agonist [D-Trp6]LH-RH did not protect the rat testes exposed to 622 rads and, at most, only partially protected against 415 rads. These results suggest that pretreatment with LH-RH antagonists and possibly agonists, might decrease the testicular damage caused by radiation and accelerate the recovery of reproductive functions.