Probing studies on multiple dose effects of antide (Nal-Lys) GnRH antagonist in ovariectomized monkeys.

ABSTRACT

This study was designed to extend evaluation of the long-acting effects of a "third generation" Antide (Nal-Lys) GnRH antagonist on gonadotropin secretion in ovariectomized (OVX) monkeys, with special attention to recrudescence of pituitary gonadotropin secretion after multiple dose treatments, as well as pituitary secretory responsiveness to GnRH. The duration of FSH/LH inhibition by Antide was dose-dependent, as well as being much longer than for Nal-Glu GnRHant; however, full recrudescence of gonadotropin secretion, albeit gradual, did occur. The acute LH secretory response to serial iv boluses of GnRH, in the face of GnRHant-induced suppression of gonadotropin secretion, was transiently accelerated and biologically active. Thereafter, the state of FSH/LH inhibition was resumed chronically. Thus, treatment with Antide produced profound long-term inhibition of tonic gonadotropin levels, yet hyper-responsiveness to exogenous GnRH administration was maintained throughout.