Administration of a GnRH-antagonist to immature rats affects subsequent female and male pubertal development differently.
Gonadotropin secretion was inhibited in immature male and female rats by sc administration of the GnRH-antagonist ORG30276 (GnRH-A) on days 6, 9, 12 and 15. In GnRH-A-treated females this resulted in suppression of the temporarily increased plasma LH and FSH levels, which normally occur in prepubertal female rats. Ovarian weight was decreased. Although vaginal opening in GnRH-A-treated rats occurred earlier, the age of 1st estrus and the number of ova shed at first ovulation were not affected. Fertility at 4 months of age was normal. After initial suppression of gonadotropin levels, the FSH levels in GnRH-A-treated males, however, sharply increased to about twice the control levels. Plasma FSH remained elevated at least until 4 months of age. The LH levels at adult age were not affected by antagonist treatment and neither were testosterone levels. Testicular weight was decreased by GnRH-A from about 50% on day 15 to about 30% at 4 months of age. Pubertal development as measured by balano-preputial separation was delayed by about 7-10 days. At 4 months of age fertility was decreased. Thus, suppression of early gonadotropin secretion by GnRH-A treatment had dramatic effects on subsequent pubertal development in the male, but not in the female rat.
van den Dungen
H M
HM
Department of Pharmacology, University of Leiden, The Netherlands.
van Dieten
J A
JA
Tilders
F J
FJ
van Rees
G P
GP
Schoemaker
J
J
D000367:Age Factors; D000818:Animals; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012741:Sexual Maturation / Q000187:drug effects*; D013739:Testosterone / Q000097:blood
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C042691:LHRH, N-acetyl-(4-chlorophenylalanyl)(1)-(4-chlorophenylalanyl)(2)-tryptophyl(3)-arginyl(6)-alanine(10)-; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone