GnRH antagonist cetrorelix prevents sexual maturation of peripubertal malerats

Gonadotropin releasing-hormone (GnRH) analogues contain amino acid substitu tions of the native decapeptide. Depending on the substitutions, the analog ues have GnRH agonistic or antagonistic properties. GnRH agonists are the e stablished treatment in cases of central precocious puberty caused by prema ture activation of the hypothalamic GnRH pulse generator. Much less data ex ist on the use of GnRH antagonists to influence the onset of puberty. Using the GnRH antagonist cetrorelix we conducted a 5 day treatment of peripuber tal male rats (cetrorelix group n=12, 100 mu g/d intraperitoneally injected ; placebo n=10, NaCl 0.9% intraperitoneally injected) from postnatal day 32 to 36 and decapitated on postnatal day 37 to investigate the effects on pu bertal development, serum gonadotropin and testosterone levels as well as t he GnRH release from explanted hypothalami. A control group of 5 male rats was added for hypothalamus superfusion experiments on day 25. We observed n o progress of testicular development in the cetrorelix group. Cetrorelix in jected rats had lower testicular weights (531+/-13 versus controls 819+/-25 mg, mean+/-SEM, p<0.0001). 12 h after the last injection testosterone leve ls were in the castrate range (serum testosterone, median controls: 1.7 ng/ ml, median cetrorelix <0.30 ng/ml, p<0.001), and they showed lower serum LH and FSH compared to the same age placebo group. After decapitation the pre optic mediobasal hypothalamic area (POA/MBH) was dissected from 5 randomly selected rats from each treatment group and the release rates of GnRH were determined in superfusion experiments: The hypothalamic GnRH secretion was comparable in the CET and the same age placebo rats but significantly highe r than in the 25 day old control group. Conclusion: The GnRH antagonist cet rorelix inhibits the pituitary-gonadal axis in peripubertal male rats and m ay be effective in treating central precocious puberty in males.