Klingmüller D, Schepke M, Enzweiler C, Bidlingmaier F
Department of Clinical Biochemistry, University of Bonn, Germany.
Acta Endocrinol (Copenh). 1993 Jan;128(1):15-8. doi: 10.1530/acta.0.1280015.
GnRH antagonists, unlike the GnRH agonists, immediately suppress gonadotropins and testosterone secretion without initial stimulatory effect. We report here on a single-dose study with the new GnRH antagonist Cetrorelix (Ac-D-Nal(2)1, D-Phe(4C1)2, D-Pal3, D-Cit6, D-Alal0) in 25 normal men. The study involved five different dose groups (0.25, 0.5, 1.0, 1.5 or 3.0 mg) and subjects were observed over a 40 h period. Five men served as controls. Serum levels of LH, FSH and testosterone decreased rapidly with a dose-related decline for testosterone of 25%, 24%, 41%, 53% and 72%, respectively, for testosterone within the first 8 h of antagonist administration. All effects were reversible and no serious side effects were observed. Thus, this GnRH antagonist is active in men even in small doses and could become a new therapeutic tool for sex hormone-dependent diseases. Cetrorelix seems to have the highest suppressive rate per mg peptide of all other antagonists from the literature, such as Nal-Glu (Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal3, Arg5, D-Glu6(AA), D-Alal0), Detirelix (Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Alal0) or 4F (Ac-delta 3Prol, 4F-D-Phe2, D-Trp3,6). During the time of suppression after a dose of 3 mg there was an LH and testosterone peak in the early morning coinciding with the testosterone peak in untreated men. The GnRH antagonist seems to unmask the circadian rhythm of LH secretion.
促性腺激素释放激素（GnRH）拮抗剂与GnRH激动剂不同，它能立即抑制促性腺激素和睾酮分泌，且无初始刺激作用。我们在此报告一项针对25名正常男性使用新型GnRH拮抗剂西曲瑞克（Ac-D-Nal(2)1, D-Phe(4C1)2, D-Pal3, D-Cit6, D-Alal0）的单剂量研究。该研究包括五个不同剂量组（0.25、0.5、1.0、1.5或3.0毫克），并对受试者进行了40小时的观察。五名男性作为对照。在给予拮抗剂后的前8小时内，促黄体生成素（LH）、促卵泡生成素（FSH）和睾酮的血清水平迅速下降，睾酮下降与剂量相关，分别为25%、24%、41%、53%和72%。所有作用均可逆，未观察到严重副作用。因此，这种GnRH拮抗剂即使小剂量在男性中也有活性，可能成为治疗性激素依赖性疾病的新治疗工具。从文献来看，西曲瑞克每毫克肽的抑制率似乎高于所有其他拮抗剂，如那法瑞林（Nal-Glu，Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal3, Arg5, D-Glu6(AA), D-Alal0）、地来瑞林（Detirelix，Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Alal0）或4F（Ac-delta 3Prol, 4F-D-Phe2, D-Trp3,6）。在给予3毫克剂量后的抑制期内，清晨出现LH和睾酮峰值，与未治疗男性的睾酮峰值一致。这种GnRH拮抗剂似乎揭示了LH分泌的昼夜节律。
