Effect of pretreatment of long-term ovariectomized rats with an LRH antagonist on LH release in vitro by LRH, elevated K+ or N6-monobutyryl adenosine 3',5'-monophosphate (mbcAMP) plus theophylline.

The effect of the LRH antagonist (Ac-D-p-Cl-Phe1,2,D-Trp3,D-Phe6-D-Ala10)LRH (Org 30093) on pituitary LH release was studied, using pituitary glands of ovariectomized rats. In vitro, the antagonist had no detectable agonist activity in the concentration used, had no effect on the maximal LH release which can be induced by LRH and shifted the dose-response line of LRH to the right, without changing its slope. By this the antagonist fulfilled the conditions of purely competitive antagonist. Also, when present in vitro, the antagonist had no effect on LH release induced by raised K+, whether alone or in combination with mbcAMP plus theophylline. A single injection of Org 30093 decreased serum LH without inducing a change of pituitary LH content measured 24 h later. Twenty-four h after the sc injection of the agonist, LH release in vitro induced by LRH was affected differently, depending on the concentration of LRH used: the effect of low concentrations of LRH was inhibited, whereas the effect of high concentrations of LRH was augmented. Pretreatment with the agonist had no effect on LH release by raised K+ combined with mbcAMP plus theophylline, but slightly increased LH release by raised K+.