Further Studies on the Inhibitory Effect of [D‐A1a6, des‐Gly‐NH210]LHRH Ethylamide on Spermatogenesis and Steroidogenesis in the Rat: Reversibility and Effect of Androgen Administration

Abstract

Following the recent observation that chronic treatment with [D‐Ala6, des‐Gly‐NH210]LHRH ethylamide, a potent LHRH agonist, leads to an almost complete degeneration of seminiferous tubules in the rat, the time‐course of recovery of spermatogenesis after cessation of treatment was investigated. Adult rats injected with the LHRH agonist (100 ng, every second day) for four weeks were studied four, eight, and 16 weeks later. Although progressive improvement was noted from four to 16 weeks after cessation of treatment, about 25% of tubules still appeared completely degenerated at the end of the recuperation period. One month following cessation of treatment, testicular LH and prolactin receptor concentrations, testicular testosterone (T) and dihydrotestosterone (DHT) levels, and ventral prostate and seminal vesicle weights had returned to normal values. Testis weight, however, which was decreased by 40% one month after treatment with the LHRH analog, increased more slowly toward normal and was still at 85% of control value four months after treatment. Plasma LH and FSH levels, which were increased approximately 100% after treatment with the LHRH analogue, returned to within normal values between one and two months following cessation of treatment, respectively. Administration of androgens (T or DHT) concomitantly with the LHRH agonist only partially prevented the deleterious effects of the peptide on spermatogenesis. On the other hand, administration of the LHRH agonist had no effect on testicular morphology in hypophysectomized rats. These data show a rapid return to normal of the hypophyseal testicular elements responsible for androgen formation after desensitization by LHRH agonist treatment in adult rats. These results suggest that the inhibitory effect of chronic LHRH agonist administration on spermatogenesis is at least partially reversible, and that a decrease in androgen production is probably not the only factor involved in the inhibition of spermatogenesis by LHRH agonist treatment.