Chronic Effects of [D-Trp6-Pro9-NEt]Luteinizing Hormone-Releasing Factor on Reproductive Processes in the Female Rat*

Chronic administration of a potent LRF agonist, [D-Trp6,Pro9-NEt]LFR (A), to intact adult male rats induced a dose-related decrease in testicular and accessory organ weights, diminished production of testosterone (T), and disrupted tubular morphology, indicative of suppression of spermatogenesis. Transient elevations of plasma progesterone levels and a marked reduction of PRL secretion were also observed in A-treated rats. The effects of A on testicular weights, T levels, and seminiferous tubule morphology were already apparent 3 days after the first injection. Administration of A was equally effective when administered daily or at 1- to 4-day intervals in lowering steroid levels and testicular weights. After a 1-week daily exposure to A, seminal vesicles and prostate weights as well as T levels returned to control values within 1--2 weeks. Testicular weights, however, were still depressed 4 weeks after cessation of treatment, and germinal epithelium was disrupted in 30--40% of the tubules. Measurement of T and LH plasma levels after each daily injection of A indicated a blunting of succeeding A-induced elevations of LH and T, which lasted up to 72 h after a single administration of A. The observation that cultured pituitary cells repeatedly exposed to A showed a similar blunting of LRF-induced LH elevation suggests that the decrease in pituitary responsiveness was not exclusively due to steroid feedback. Administration of T propionate to A-treated intact rats was unable to restore normal testicular weights and seminiferous tubule morphology, whereas in hypophysectomized rats, T propionate maintained qualitatively normal spermatogenesis even in the presence of A. These results coupled with the observation that high levels of hCG and PMS gonadotropin had effects similar to those of A on the tubular morphology of intact rats suggest the importance of pituitary secretion in mediating the deleterious effects of A on reproductive functions in the male rat.