Inhibitory effect of a highly potent antagonist of LH releasing hormone (SB-75) on the pituitary gonadal axis in the intact and castrated rat.
The biological potency of the new, highly potent antagonist [AC-D-Nal (2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10] LH-RH (SB-75) on the pituitary-gonadal system of female castrated and intact ovulating rats was tested. Administration of a single dose (50-100 micrograms/kg BW) of the antagonist SB-75 inhibited effectively the elevated gonadotrophin levels for 48 h. Pituitary LH and FSH content was not affected by SB-75 treatment. When administered in the early afternoon of the proestrus to intact cycling rats, SB-75 blocked the preovulatory LH surge as well as the primary and secondary FSH surges. However, the secondary FSH surge was not affected by SB-75 treatment when administered on the evening of proestrus suggesting its independence from the LH-RH mechanism. A group of ovariectomized rats was chronically treated with D-Trp6-LH-RH after having been pretreated by administration of a single dose of the antagonist. The initial stimulatory release of LH and FSH initiated by injection of the LH-RH agonist was significantly reduced by pretreatment with the LH-RH antagonist. We conclude that the LH-RH antagonist SB-75 may be used effectively in the field of reproductive dysfunction and endocrinological oncology and may become an invaluable physiological probe in studying the hormonal dynamics of the reproductive endocrine axis.
Ayalon
D
D
Timsit Institute of Reproductive Endocrinology, Sourasky Medical Center of Tel Aviv, Israel.
Farhi
Y
Y
Comaru-Schally
A M
AM
Schally
A V
AV
Eckstein
N
N
Vagman
I
I
Limor
R
R
D000818:Animals; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood; D010052:Ovariectomy; D010053:Ovary / Q000187:drug effects*; D010902:Pituitary Gland / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011966:Receptors, LHRH / Q000187:drug effects; D012016:Reference Values; D017329:Triptorelin Pamoate / Q000494:pharmacology
D011966:Receptors, LHRH; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C062876:cetrorelix