Effect of estradiol on the secretion of LH in the GnRH-pretreated rat after treatment with the GnRH-antagonist, Org 30093.

LH responses induced in the long-term ovariectomized rat by GnRH or GnRH agonistic analogue are augmented by E2. The augmentation by E2 does not occur during, but after termination of GnRH pretreatment. In this study it was investigated whether the augmenting effect of E2 develops also in the GnRH-pretreated rat when the animals were treated with GnRH antagonistic analogue. Two weeks after ovariectomy rats were treated for 10 days with 250 ng GnRH/h (GnRH-rats), released by sc implanted osmotic minipumps. Control rats received a Silastic 'sham pump'. Rats were simultaneously treated with solvent (oil) or estradiol benzoate (EB, 3 micrograms, sc). Each group of rats was divided into two subgroups, one receiving solvent, the other the GnRH antagonist, Org 30093 (ANT, 100 micrograms/injection) on 3 consecutive days. In Experiment 1, the pituitary LH content and the LH secretion following stimulation with the agonistic GnRH analogue buserelin, were measured, in Experiment 2, the plasma concentrations of LH before and after cessation of ANT treatment. The effects of treatment with GnRH, EB and ANT were studied on the basis of 1) the height of the maximal LH response and 2) the half-maximally effective dose (ED50) of buserelin. Experiment 1 revealed that GnRH depleted the pituitary gland to about 42% of its original LH content. In EB-treated GnRH-rats the depletion was even stronger (to 14%). After ANT treatment, the pituitary glands of the GnRH-rats were (partly) repleted (oil: to 65%; EB: to 31%).(ABSTRACT TRUNCATED AT 250 WORDS)