Antagonist of Gonadotropin-Releasing Hormone Blocks Naloxone-induced Elevations in Serum Luteinizing Hormone

Abstract

Administration of a gonadotropin-releasing hormone (GnRH) antagonist, [D-pGlu¹, D-Phe², D-Trp^3,6]-GnRH, to immature female rats blocks the equivalent elevations in serum luteinizing hormone (LH) which are provoked by exogenous, natural GnRH (8 ng/100 g BW) or naloxone (0.25 mg/100 g BW), a specific opiate antagonist. A significant inhibition of GnRH- or naloxone-induced release of LH is obtained when rats are pretreated for 0, 15, 30 or 60 min with 5,000 ng/100 g BW of GnRH antagonist but no inhibition is evident when the antagonist is injected 180 min before either stimulant of LH secretion. A similar time-course is observed for GnRH antagonist inhibition of basal LH levels. The minimally effective dose of GnRH antagonist for suppressing both GnRH- and naloxone-induced LH release is 1,000 ng/100 g BW. More than 80% of the LH response to GnRH or naloxone is blocked by the highest tested dose (10,000 ng/100 g BW) of GnRH antagonist. Since naloxone has no direct influence on pituitary release of LH, these similar influences of GnRH antagonist on the LH-releasing properties of natural GnRH and naloxone, strongly suggest that the systemic administration of the opiate antagonist, naloxone, stimulates the release of endogenous GnRH.