Tags

Type your tag names separated by a space and hit enter

GnRH antagonist cetrorelix prevents sexual maturation of peripubertal male rats.
Exp Clin Endocrinol Diabetes 2000; 108(5):358-63EC

Abstract

Gonadotropin releasing-hormone (GnRH) analogues contain amino acid substitutions of the native decapeptide. Depending on the substitutions, the analogues have GnRH agonistic or antagonistic properties. GnRH agonists are the established treatment in cases of central precocious puberty caused by premature activation of the hypothalamic GnRH pulse generator. Much less data exist on the use of GnRH antagonists to influence the onset of puberty. Using the GnRH antagonist cetrorelix we conducted a 5 day treatment of peripubertal male rats (cetrorelix group n=12, 100 microg/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 pubertal development, serum gonadotropin and testosterone levels as well as the GnRH release from explanted hypothalami. A control group of 5 male rats was added for hypothalamus superfusion experiments on day 25. We observed no progress of testicular development in the cetrorelix group. Cetrorelix injected rats had lower testicular weights (531+/-13 versus controls 819+/-25 mg, mean+/-SEM, p<0.0001). 12 h after the last injection testosterone levels 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 preoptic 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 higher than in the 25 day old control group.

CONCLUSION

The GnRH antagonist cetrorelix inhibits the pituitary-gonadal axis in peripubertal male rats and may be effective in treating central precocious puberty in males.

Authors+Show Affiliations

Children's Hospital, University of Göttingen, Germany. croth@med.uni-goettingen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10989955

Citation

Roth, C, et al. "GnRH Antagonist Cetrorelix Prevents Sexual Maturation of Peripubertal Male Rats." Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association, vol. 108, no. 5, 2000, pp. 358-63.
Roth C, Leonhardt S, Seidel C, et al. GnRH antagonist cetrorelix prevents sexual maturation of peripubertal male rats. Exp Clin Endocrinol Diabetes. 2000;108(5):358-63.
Roth, C., Leonhardt, S., Seidel, C., Lakomek, M., Wuttke, W., & Jarry, H. (2000). GnRH antagonist cetrorelix prevents sexual maturation of peripubertal male rats. Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association, 108(5), pp. 358-63.
Roth C, et al. GnRH Antagonist Cetrorelix Prevents Sexual Maturation of Peripubertal Male Rats. Exp Clin Endocrinol Diabetes. 2000;108(5):358-63. PubMed PMID: 10989955.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GnRH antagonist cetrorelix prevents sexual maturation of peripubertal male rats. AU - Roth,C, AU - Leonhardt,S, AU - Seidel,C, AU - Lakomek,M, AU - Wuttke,W, AU - Jarry,H, PY - 2000/9/16/pubmed PY - 2001/3/3/medline PY - 2000/9/16/entrez SP - 358 EP - 63 JF - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association JO - Exp. Clin. Endocrinol. Diabetes VL - 108 IS - 5 N2 - UNLABELLED: Gonadotropin releasing-hormone (GnRH) analogues contain amino acid substitutions of the native decapeptide. Depending on the substitutions, the analogues have GnRH agonistic or antagonistic properties. GnRH agonists are the established treatment in cases of central precocious puberty caused by premature activation of the hypothalamic GnRH pulse generator. Much less data exist on the use of GnRH antagonists to influence the onset of puberty. Using the GnRH antagonist cetrorelix we conducted a 5 day treatment of peripubertal male rats (cetrorelix group n=12, 100 microg/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 pubertal development, serum gonadotropin and testosterone levels as well as the GnRH release from explanted hypothalami. A control group of 5 male rats was added for hypothalamus superfusion experiments on day 25. We observed no progress of testicular development in the cetrorelix group. Cetrorelix injected rats had lower testicular weights (531+/-13 versus controls 819+/-25 mg, mean+/-SEM, p<0.0001). 12 h after the last injection testosterone levels 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 preoptic 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 higher than in the 25 day old control group. CONCLUSION: The GnRH antagonist cetrorelix inhibits the pituitary-gonadal axis in peripubertal male rats and may be effective in treating central precocious puberty in males. SN - 0947-7349 UR - https://www.unboundmedicine.com/medline/citation/10989955/GnRH_antagonist_cetrorelix_prevents_sexual_maturation_of_peripubertal_male_rats_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-2000-8129 DB - PRIME DP - Unbound Medicine ER -