The antifertility effects of the antagonistic analogue N-Ac-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10-LH-RH (ORG 30276) were investigated in male and female rats. Male rats were treated with ORG 30276 at doses of 10 μg/kg, 100 μg/kg, or 1000 μg/kg per day for 60 days. The control rats were injected with the vehicle only. The treatment with the highest dose of the antagonist caused a significant decrease in the weights of the anterior pituitaries, testes, seminal vesicles, and ventral prostates and reduced serum and pituitary LH levels. The intermediate dose of the antagonist affected only seminal vesicle weights. The histology of the testes from the rats treated with the highest dose showed that the spermatogenesis was markedly depressed and did not advance beyond the stage of spermatocyte I; the interstitium showed cells of fibroblastic appearance. Twenty days after stopping treatment with the highest dose of the analogue there was a marked recovery of the weight of the testes, seminal vesicles, and ventral prostates. However, the animals were still infertile when caged with female rats. Sixty days after treatment the animals had recovered testicular function and fertility. The offspring were normal, with no evidence of genetic abnormalities. Female rats were injected with ORG 30276 at doses of 10 μg/kg, 100 μg/kg, or 1000 μg/kg per day for 14 days. The treatment with ORG 30276 did not modify body weights, but anterior pituitary and uterine weights were significantly decreased in the group of rats treated with the highest dose of the antagonist. Ovarian weights were decreased significantly in all the three groups treated with ORG 30276. The animals treated with 1000 μg/kg of ORG 30276 had significantly lower serum LH and FSH and diestrous vaginal smears indicating a blockade of ovulation. The fertility of rats was checked every 15 days after stopping the treatment with ORG 30276. At 15 and 30 days after the last injection of ORG 30276, most of the rats were fertile when caged with male rats. The analogue did not have any teratologic effects, since no apparent abnormalities were seen in the offspring. These results indicate that treatment with ORG 30276 suppresses gonadal function and that the effect is reversible. Once the gonads recover their function after the withdrawal of the treatment, fertility is restored in both male and female rats. This investigation shows that LH-RH antagonists can be used as the basis for a new method of contraception. Side effects and future development of LH-RH antagonists are discussed.
|Original language||English (US)|
|Number of pages||9|
|Journal||International Journal of Fertility|
|State||Published - Jan 1 1986|
ASJC Scopus subject areas
- Obstetrics and Gynecology