Daneshdoost L, Pavlou S N, Molitch M E, Gennarelli T A, Savino P J, Sergott R C, Bosley T M, River J E, Vale W W, Snyder P J
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
J Clin Endocrinol Metab. 1990 Jul;71(1):92-7. doi: 10.1210/jcem-71-1-92.
As a preliminary step in searching for a pharmacological treatment for gonadotroph adenomas, we administered the GnRH antagonist analog Nal-Glu GnRH to five patients, four men and a woman, with FSH-secreting gonadotroph adenomas in order to determine its effect on FSH secretion. Administration of a single 10-mg dose of Nal-Glu GnRH to four of the patients produced a significant decrease in the serum FSH concentration in two patients and returned the FSH level to normal in only one. Administration of 5 mg Nal-Glu every 12 h for 7 days, however, produced a significant (P less than 0.001) decrease, and to within the normal range, in four of the five patients (mean +/- SEM, 32.7 +/- 5.6 IU/L during the 3 days before treatment and 9.8 +/- 1.4 IU/L during the last 3 days of treatment). Also, in response to the 7-day treatment, LH fell significantly in all five patients, alpha-subunit fell in three, and testosterone fell in all four men. Administration for 6 weeks of the GnRH agonist analog leuprolide did not decrease the serum FSH concentration of one of the patients whose serum FSH did decrease in response to Nal-Glu GnRH. We conclude that repetitive administration of Nal-Glu GnRH may often inhibit FSH secretion by gonadotroph adenomas and that FSH secretion by gonadotroph adenomas may be dependent on endogenous GnRH secretion.
作为寻找促性腺激素腺瘤药物治疗方法的初步步骤,我们对5例促卵泡激素(FSH)分泌型促性腺激素腺瘤患者(4名男性和1名女性)给予促性腺激素释放激素(GnRH)拮抗剂类似物Nal-Glu GnRH,以确定其对FSH分泌的影响。对4例患者单次给予10 mg剂量的Nal-Glu GnRH后,2例患者的血清FSH浓度显著下降,仅1例患者的FSH水平恢复正常。然而,每12小时给予5 mg Nal-Glu,持续7天,5例患者中有4例出现显著(P<0.001)下降,且降至正常范围内(治疗前3天均值±标准误为32.7±5.6 IU/L,治疗最后3天为9.8±1.4 IU/L)。此外,在7天的治疗过程中,所有5例患者的促黄体生成素(LH)均显著下降,3例患者的α亚基下降,所有4名男性患者的睾酮下降。对1例血清FSH在给予Nal-Glu GnRH后下降的患者给予GnRH激动剂类似物亮丙瑞林治疗六周,其血清FSH浓度并未下降。我们得出结论,重复给予Nal-Glu GnRH通常可能抑制促性腺激素腺瘤分泌FSH,且促性腺激素腺瘤分泌FSH可能依赖于内源性GnRH分泌。