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Comparative analysis of different puberty inhibiting mechanisms of two GnRH agonists and the GnRH antagonist cetrorelix using a female rat model.
Pediatr Res 2000; 48(4):468-74PR

Abstract

GnRH agonists are the established treatment of precocious puberty caused by premature stimulation of gonadotropin secretion. It has been reported that after an initial stimulation ("flare-up") they reduce LH secretion by desensitization of pituitary GnRH receptors. Little has been published about the use of GnRH antagonists such as cetrorelix to control the onset of puberty and whether they are potentially advantageous compared with GnRH agonists. We conducted two multigroup experiments (12 and 10 d, respectively) treating prepubertal/peripubertal female rats with either the GnRH agonist triptorelin or buserelin and compared them with rats treated with the GnRH antagonist cetrorelix and controls to assess the effects on pubertal progress and serum hormones. In the second experiment, the effects of buserelin and cetrorelix on gene expression of the GnRH receptor, LH-beta, FSH-beta, and the alpha subunit genes in the pituitary were also investigated. Cetrorelix, triptorelin, and buserelin retarded the onset of puberty as determined by delayed vaginal opening, lower ovarian weights, and lower serum estradiol levels. However, although LH and FSH levels were stimulated by both agonists, they were inhibited by cetrorelix. In the cetrorelix versus buserelin experiment, pituitary gene expression of the GnRH receptor and LH-beta subunit were significantly lower in cetrorelix treated rats compared with controls whereas buserelin had little effect. Expression of FSH-beta and alpha subunit were stimulated by buserelin but not by cetrorelix. Even though all three of these GnRH analogues inhibited gonadal development and delayed the onset of puberty, the GnRH agonists had stimulating and inhibiting effects on the pituitary-gonadal axis whereas cetrorelix exerted only inhibiting effects. We conclude from this female rat model that cetrorelix may offer advantages for a more controlled medical treatment of precocious puberty compared with GnRH agonist treatment.

Authors+Show Affiliations

Children's Hospital, University of Göttingen, Göttingen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11004237

Citation

Roth, C, et al. "Comparative Analysis of Different Puberty Inhibiting Mechanisms of Two GnRH Agonists and the GnRH Antagonist Cetrorelix Using a Female Rat Model." Pediatric Research, vol. 48, no. 4, 2000, pp. 468-74.
Roth C, Leonhardt S, Seidel C, et al. Comparative analysis of different puberty inhibiting mechanisms of two GnRH agonists and the GnRH antagonist cetrorelix using a female rat model. Pediatr Res. 2000;48(4):468-74.
Roth, C., Leonhardt, S., Seidel, C., Luft, H., Wuttke, W., & Jarry, H. (2000). Comparative analysis of different puberty inhibiting mechanisms of two GnRH agonists and the GnRH antagonist cetrorelix using a female rat model. Pediatric Research, 48(4), pp. 468-74.
Roth C, et al. Comparative Analysis of Different Puberty Inhibiting Mechanisms of Two GnRH Agonists and the GnRH Antagonist Cetrorelix Using a Female Rat Model. Pediatr Res. 2000;48(4):468-74. PubMed PMID: 11004237.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative analysis of different puberty inhibiting mechanisms of two GnRH agonists and the GnRH antagonist cetrorelix using a female rat model. AU - Roth,C, AU - Leonhardt,S, AU - Seidel,C, AU - Luft,H, AU - Wuttke,W, AU - Jarry,H, PY - 2000/9/27/pubmed PY - 2000/10/21/medline PY - 2000/9/27/entrez SP - 468 EP - 74 JF - Pediatric research JO - Pediatr. Res. VL - 48 IS - 4 N2 - GnRH agonists are the established treatment of precocious puberty caused by premature stimulation of gonadotropin secretion. It has been reported that after an initial stimulation ("flare-up") they reduce LH secretion by desensitization of pituitary GnRH receptors. Little has been published about the use of GnRH antagonists such as cetrorelix to control the onset of puberty and whether they are potentially advantageous compared with GnRH agonists. We conducted two multigroup experiments (12 and 10 d, respectively) treating prepubertal/peripubertal female rats with either the GnRH agonist triptorelin or buserelin and compared them with rats treated with the GnRH antagonist cetrorelix and controls to assess the effects on pubertal progress and serum hormones. In the second experiment, the effects of buserelin and cetrorelix on gene expression of the GnRH receptor, LH-beta, FSH-beta, and the alpha subunit genes in the pituitary were also investigated. Cetrorelix, triptorelin, and buserelin retarded the onset of puberty as determined by delayed vaginal opening, lower ovarian weights, and lower serum estradiol levels. However, although LH and FSH levels were stimulated by both agonists, they were inhibited by cetrorelix. In the cetrorelix versus buserelin experiment, pituitary gene expression of the GnRH receptor and LH-beta subunit were significantly lower in cetrorelix treated rats compared with controls whereas buserelin had little effect. Expression of FSH-beta and alpha subunit were stimulated by buserelin but not by cetrorelix. Even though all three of these GnRH analogues inhibited gonadal development and delayed the onset of puberty, the GnRH agonists had stimulating and inhibiting effects on the pituitary-gonadal axis whereas cetrorelix exerted only inhibiting effects. We conclude from this female rat model that cetrorelix may offer advantages for a more controlled medical treatment of precocious puberty compared with GnRH agonist treatment. SN - 0031-3998 UR - https://www.unboundmedicine.com/medline/citation/11004237/Comparative_analysis_of_different_puberty_inhibiting_mechanisms_of_two_GnRH_agonists_and_the_GnRH_antagonist_cetrorelix_using_a_female_rat_model_ L2 - http://dx.doi.org/10.1203/00006450-200010000-00009 DB - PRIME DP - Unbound Medicine ER -