DT-Web

DB00644 - Gonadorelin


Identification
Name Gonadorelin
Accession Number DB00644 (APRD01001)
Type small molecule
Description Gonadorelin is another name for gonadotropin-releasing hormone (GnRH). It is a synthetic decapeptide prepared using solid phase peptide synthesis. GnRH is responsible for the release of follicle stimulating hormone and leutinizing hormone from the anterior pitutitary.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 1182.2901
Groups approved
Monoisotopic Weight 1181.573025571
Pharmacology
Indication For evaluating the functional capacity and response of the gonadotropes of the anterior pituitary also for evaluating residual gonadotropic function of the pituitary following removal of a pituitary tumor by surgery and/or irradiation.
Mechanism of action Systemic - Like naturally occurring gonadotropin-releasing hormone (GnRH), gonadorelin primarily stimulates the synthesis and release of luteinizing hormone (LH) from the anterior pituitary gland. Follicle-stimulating hormone (FSH) production and release is also increased by gonadorelin, but to a lesser degree. In prepubertal females and some gonadal function disorders, the FSH response may be greater than the LH response. For the treatment of amenorrhea, delayed puberty, and infertility the administration of gonadorelin is used to simulate the physiologic release of GnRH from the hypothalamus in treatment of delayed puberty, treatment of infertility caused by hypogonadotropic hypogonadism, and induction of ovulation in those women with hypothalamic amenorrhea. This results in increased levels of pituitary gonadotropins LH and FSH, which subsequently stimulate the gonads to produce reproductive steroids.
Absorption Rapidly absorbed when injected
Protein binding Not Available
Biotransformation Rapidly hydrolyzed to inactive peptide components
Route of elimination Not Available
Toxicity LD50>3000 mg/kg (rat, oral)
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Gonadotropin-releasing hormone receptor
Name Gonadotropin-releasing hormone receptor
Gene Name GNRHR
Pharmacological action yes
Actions agonist
References
  • Lu ZL, Gallagher R, Sellar R, Coetsee M, Millar RP: Mutations remote from the human gonadotropin-releasing hormone (GnRH) receptor-binding sites specifically increase binding affinity for GnRH II but not GnRH I: evidence for ligand-selective, receptor-active conformations. J Biol Chem. 2005 Aug 19;280(33):29796-803. Epub 2005 Jun 20. - Pubmed
  • Moles G, Carrillo M, Mananos E, Mylonas CC, Zanuy S: Temporal profile of brain and pituitary GnRHs, GnRH-R and gonadotropin mRNA expression and content during early development in European sea bass (Dicentrarchus labrax L.). Gen Comp Endocrinol. 2007 Jan 1;150(1):75-86. Epub 2006 Sep 8. - Pubmed
  • Mamputha S, Lu ZL, Roeske RW, Millar RP, Katz AA, Flanagan CA: Conserved amino acid residues that are important for ligand binding in the type I gonadotropin-releasing hormone (GnRH) receptor are required for high potency of GnRH II at the type II GnRH receptor. Mol Endocrinol. 2007 Jan;21(1):281-92. Epub 2006 Sep 14. - Pubmed
  • Lee PA, Houk CP: Gonadotropin-releasing hormone analog therapy for central precocious puberty and other childhood disorders affecting growth and puberty. Treat Endocrinol. 2006;5(5):287-96. - Pubmed
  • Bliss SP, Navratil AM, Breed M, Skinner DC, Clay CM, Roberson MS: Signaling complexes associated with the type I gonadotropin-releasing hormone (GnRH) receptor: colocalization of extracellularly regulated kinase 2 and GnRH receptor within membrane rafts. Mol Endocrinol. 2007 Feb;21(2):538-49. Epub 2006 Oct 26. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.3256
Gonadotropin-releasing hormone II receptor
Name Gonadotropin-releasing hormone II receptor
Gene Name GNRHR2
Pharmacological action yes
Actions agonist
References
  • Morgan K, Sellar R, Pawson AJ, Lu ZL, Millar RP: Bovine and ovine gonadotropin-releasing hormone (GnRH)-II ligand precursors and type II GnRH receptor genes are functionally inactivated. Endocrinology. 2006 Nov;147(11):5041-51. Epub 2006 Aug 17. - Pubmed
  • Mamputha S, Lu ZL, Roeske RW, Millar RP, Katz AA, Flanagan CA: Conserved amino acid residues that are important for ligand binding in the type I gonadotropin-releasing hormone (GnRH) receptor are required for high potency of GnRH II at the type II GnRH receptor. Mol Endocrinol. 2007 Jan;21(1):281-92. Epub 2006 Sep 14. - Pubmed
  • Marelli MM, Moretti RM, Januszkiewicz-Caulier J, Motta M, Limonta P: Gonadotropin-releasing hormone (GnRH) receptors in tumors: a new rationale for the therapeutical application of GnRH analogs in cancer patients? Curr Cancer Drug Targets. 2006 May;6(3):257-69. - Pubmed
  • Li JH, Choe H, Wang AF, Maiti K, Wang C, Salam A, Chun SY, Lee WK, Kim K, Kwon HB, Seong JY: Extracellular loop 3 (EL3) and EL3-proximal transmembrane helix 7 of the mammalian type I and type II gonadotropin-releasing hormone (GnRH) receptors determine differential ligand selectivity to GnRH-I and GnRH-II. Mol Pharmacol. 2005 Apr;67(4):1099-110. Epub 2005 Jan 5. - Pubmed
  • Silver MR, Sower SA: Functional characterization and kinetic studies of an ancestral lamprey GnRH-III selective type II GnRH receptor from the sea lamprey, Petromyzon marinus. J Mol Endocrinol. 2006 Jun;36(3):601-10. - Pubmed
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
148 Lutropin-choriogonadotropic hormone receptor LHCGR 0.2629
3811 Cytochrome P450 19A1 CYP19A1 0.0487
1649 Small inducible cytokine A2 CCL2 0.0242
756 Sex hormone-binding globulin SHBG 0.017
614 Progesterone receptor PGR 0.0157
146 Androgen receptor AR 0.0135
136 Estrogen receptor ESR1 0.0125
4512 Cytochrome P450 3A4 CYP3A4 0.0079
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