Goserelin is a synthetic gonadotropin-releasing hormone (GNRH) agonist that binds to the GNRH receptor (GNRHR; Ki = 1.6 nM, in CHO cells expressing the human receptor).1 It binds to mouse pituitary αT3-1 cells and human placenta (Kds = 2 and 580 nM, respectively) and increases intracellular calcium in αT3-1 cells.2 Goserelin induces testosterone production in vitro within 4 h in rat Leydig cells (ED50 = 83 nM) but decreases testosterone plasma level in vivo in rats over a period of 2 to 24 weeks.3,4 It inhibits tumor growth in a DU145 human prostate carcinoma mouse xenograft model when administered at a dose of 100 μg per day.5 Formulations containing goserelin have been used in the treatment of hormone-dependent breast and prostate cancers, as well as endometriosis and uterine fibroids.
1.Nederpelt, I., Georgi, V., Schiele, F., et al.Characterization of 12 GnRH peptide agonists - a kinetic perspectiveBr. J. Pharmacol.173(1)128-141(2016) 2.Chatzaki, E., Bax, C.M., Eidne, K.A., et al.The expression of gonadotropin-releasing hormone and its receptor in endometrial cancer, and its relevance as an autocrine growth factorCancer Res.56(9)2059-2065(1996) 3.Sullivan, M.H., and Cooke, B.A.The role of calcium in luteinizing hormone-releasing hormone agonist (ICI 118630)-stimulated steroidogenesis in rat Leydig cellsBiochem. J.218(2)621-624(1984) 4.Ward, J.A., Furr, B.J., Valcaccia, B., et al.Prolonged suppression of rat testis function by a depot formulation of Zoladex, a GnRH agonistJ. Androl.10(6)478-486(1989) 5.Dondi, D., Moretti, R.M., Montagnani, M.M., et al.Growth-inhibitory effects of luteinizing hormone-releasing hormone (LHRH) agonists on xenografts of the DU 145 human androgen-independent prostate cancer cell line in nude miceInt. J. Cancer76(4)506-511(1998)