Pituitary receptor binding activity of active, inactive, superactive and inhibitory analogs of gonadotropin-releasing hormone.

We have previously described the binding of biologically active ¹²⁵I gonadotropin-releasing hormone to the 10,800 × g membrane fraction prepared from 7-day castrate adult female rat anterior pituitary glands. Specific binding with two equilibrium association constants (10⁹ liters per mole and 10⁵ liters per mole) was found and an equilibrium competitive binding radio-receptor assay established. In order to further characterize the gonadotropin-releasing hormone receptor, 20 synthetic analogs with known bioactivity were tested in the radioreceptor assay. In vivo biological activity correlated with high affinity receptor binding but not with low affinity binding. Inhibitory analogs with no in vivo biological activity and weak antagonistic properties did not bind, while in vivo active or superactive analogs bound to high affinity receptors. These findings suggest that the high affinity gonadotropin-releasing hormone receptor binds only biologically active gonadotropin-releasing hormone like peptides and that this binding may be the initial step in gonadotropin-releasing hormone actions at the pituitary level.