Hormonal control of implantation in the rat: inhibition by luteinizing hormone-releasing hormone and its analogues.

Chronic treatment of pregnant rats with luteinizing hormone-releasing hormone (LH-RH) and its analogues (Analogue I: des-Gly10-LH-RH-ethylamide; Analogue II: des-Gly10-[D-Ala6]-LH-RH-ethylamide) inhibited implantation of the ovum. Analogues I and II were 4.5 and 173 times potent than native LH-RH in inhibiting implantation respectively. On Day 8 of the treatment with Analogue II, the pituitary glands of the pregnant rats contained approximately 10% of the amount of LH and FSH found in intact pregnant rats. By contrast, serum levels of LH were significantly higher and those of FSH significantly lower in Analogue II-treated rats than in control rats. The ovaries of Analogue II-treated rats were lighter than those of control rats because of smaller corporalutea and less developed follicles. Peripheral serum concentrations of progesterone in rats treated with LH-RH and its analogues were significantly lower than those in control rats. The peripheral serum concentration of progesterone declined earlier in rats treated with LH-RH and Analogue I than it did in rats treated with Analogue II. The inhibitory affect of Analogue II was overcome by concurrent treatment with the following combinations of hormones: progesterone + oestradiol; progesterone + human chorionic gonadotropin (hCG); prolactin + oestradiol; and prolactin + hCG. Treatment with progesterone or prolactin alone did not overcome the effect of Analogue II. These results indicate that Analogue II stimulates the production and release of LH and release of FSH to cause high ratios of LH/prolactin and LH/FSH. The induced imbalance of gonadotropins suppresses the development of ovarian follicles and corpora lutea and reduces secretion of both oestrogen and progesterone. The resulting low levels of ovarian steroids cause a delay in implantation.