GNRHR binds GNRHR peptide agonists

Stable Identifier
Reaction [binding]
Homo sapiens
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Gonadotropin-releasing hormone (GNRH) is a naturally occurring decapeptide that modulates the hypothalamic-pituitary-gonadal axis. GNHR binding to GNRH receptors causes the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which, in turn, affect the downstream synthesis and release of the sex hormones testosterone, dihydrotestosterone, estrone, and estradiol.

As full GNRHR peptide agonists, goserelin, histrelin, nafarelin (Nederpelt et al. 2016), leuprolide (Struthers et al. 2007), buserelin (Nederpelt et al. 2016b), and triptorelin (Beckers et al. 2001) bind to and initially activate downstream LH and FSH release; this initial spike in gonadotropin levels is responsible for some of the adverse effects associated with treatment (tumour flare in prostate cancer patients or pain and bleeding in women suffering from endometriosis). After 2-4 weeks of treatment, continuous stimulation of GNRHR results in feedback inhibition and significant downregulation of LH, FSH, and their corresponding downstream effects, producing a therapeutic benefit.

GNRHR agonists are primarily used to treat endometriosis and as palliative care for advanced/metastatic prostate cancer patients (Ferrero et al. 2018, Limonta & Manea 2013, Tzoupis et al. 2020). GNRHR agonists are also used to treat precocious puberty or to delay puberty in transgender youth (Shim et al. 2020, Cheuiche et al. 2021).
Literature References
PubMed ID Title Journal Year
26398856 Characterization of 12 GnRH peptide agonists - a kinetic perspective

IJzerman, AP, Schiele, F, Heitman, LH, Georgi, V, Nowak-Reppel, K, Fernández-Montalván, AE, Nederpelt, I

Br. J. Pharmacol. 2016
11726197 Structure-function studies of linear and cyclized peptide antagonists of the GnRH receptor

Reissmann, T, Kühne, R, Bernd, M, Kutscher, B, Beckers, T, Hoffmann, S

Biochem. Biophys. Res. Commun. 2001
26774084 Persistent GnRH receptor activation in pituitary αT3-1 cells analyzed with a label-free technology

Heitman, LH, Nederpelt, I, IJzerman, AP, Vergroesen, RD

Biosens Bioelectron 2016
17095587 Pharmacological characterization of a novel nonpeptide antagonist of the human gonadotropin-releasing hormone receptor, NBI-42902

Kohout, TA, Bozigian, HP, Sullivan, SK, Yang, W, Chen, C, Xie, Q, Bonneville, AK, Maki, RA, Zhu, YF, Struthers, RS, Reinhart, GJ, Chen, TK, Ling, N, Liu, XJ

Endocrinology 2007
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