Diverse effects of a potent LH-RH antagonist on the LH and FSH release.
A potent LH-RH antagonist (Ac-D-Trp1,2, D-Cpa2, D-Lys6, D-Ala10 LH-RH (Antag) was used to study the differential regulation of FSH and LH secretion by endogenous LH-RH in ovariectomized (OVX) and regularly cycling rats. The endogenous LH-RH was suppressed by single injections of Antag in OVX animals and by long-term treatment with Antag in normal and OVX rats. Serum and pituitary LH and FSH, as well as serum estradiol (E2) and progesterone (P) was determined by RIA during and/or after the treatment. The direct effect of the antagonistic analog on the ovarian P release was tested in vitro using the isolated luteal cell system. Single injections of the Antag in OVX animals caused prompt and marked suppression of the serum LH (-80%), while no decrease of the serum FSH. Long-term treatment with the same analog decreased the serum LH by 50% but did not modify the serum FSH. In normal rats, serum LH dropped to undetectable levels, while serum FSH did not change significantly. Long-term treatment with the antagonist also resulted in divergent alterations in the pituitary gonadotropin concentrations. In OVX animals, the pituitary LH content moderately elevated (+21%), however, the FSH did not change. In normal rats, ovarian cycles were interrupted, and no ovulation appeared during the treatment. The pituitary LH concentration increased by 46%, while the FSH decreased by 43%. Marked depression was found in the serum P (-60%) but no significant change in the serum E2 levels. Incubation of isolated luteal cells with the Antag did not influence the HCG-induced P secretion in vitro, demonstrating that the in vivo inhibitory effect of the antagonistic LH-RH analog on the P secretion asserts not directly on the ovarian LH-RH receptors, but through inhibition of the endogenous LH-RH. Our studies give evidence that the long-term treatment with LH-RH antagonist suppress the LH and P but not the FSH and E2 secretion, and provide new data suggesting the presence of a FSH-releasing factor in the CNS.
Kovács
M
M
Department of Anatomy, University Medical School, Pécs, Hungary.
Koppán
M
M
Mezó
I
I
Teplán
I
I
D000595:Amino Acid Sequence; D000818:Animals; D003338:Corpus Luteum / Q000166:cytology / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D004971:Estrus; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D008969:Molecular Sequence Data; D010052:Ovariectomy; D010053:Ovary / Q000033:anatomy & histology / Q000166:cytology; D010902:Pituitary Gland / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; C040278:MI 1544; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone