Effects of a luteinizing hormone-releasing hormone antagonist in late-juvenile female rats: Blockade of follicle growth and delay of first ovulation following suppression of gonadotropin concentrations

Subcutaneous injections of an antagonist against luteinizing hormone-releasing hormone (LHRH-A, Org. 30276) were administered to late-juvenile female rats. The effects on timing of vaginal opening and first ovulation on serum gonadotropin concentrations and on follicle growth were studied. The dose of 100 μg LHRH-A/100 g body wt, given on Days 28, 31, and 34, did not influence timing of first ovulation. After administration of 500 μg LHRH-A/100 g body wt, ovulation was retarded by 4.7 days if injections were given on Days 28 and 31; by 6.7 days if given on Days 28, 31, and 34; and by 11.5 days if given on Days 28, 31, 34, and 37. Serum LH and FSH concentrations 3 days after the first, second, and third injections of 500 μg LHRH-A were significantly (p < 0.01) lower than in saline-treated controls. Ovarian follicle counts showed decreased numbers of (antral) Class 2, 3, and 4 follicles 3 days after injection of 500 μg LHRH-A/100 g body wt on Day 28; a significantly higher number of Class 1 follicles and a further decrease in Class 2, 3, and 4 follicles 3 days after the second LHRH-A injection; and total absence of Class 3, 4, and 5 follicles 3 days after the third LHRH-A injection. Six days after the third LHRH-A injection, Class 3 and 4 follicles reappeared in the ovaries. A single, low-dose injection of LHRH-A administered at 0900 h on the day of first proestrus blocked first ovulation in 3 of 11 rats given 2.5 μg and in all (8/8 and 12/12) rats given 5 and 10 μg; ovulation was not blocked with 1 μg LHRH-A (0/6 rats) or saline (0/8 rats). It was concluded that administration of LHRH-A to late-juvenile female rats may delay sexual maturation by a decrease in gonadotropin levels, causing arrest of follicle growth at an early antral stage. The dose of LHRH-A needed for acute inhibition of the first ovulatory gonadotropin surge is only a fraction of that causing chronically lowered gonadotropin levels and subsequent blockade of follicle growth.