Barreca A, Cariola G, Ponzani P, Arvigo M, Foppiani L, Giordano G, Minuto F
Department of Endocrinology and Metabolism, University of Genova, Italy.
Clin Endocrinol (Oxf). 1995 Feb;42(2):161-7. doi: 10.1111/j.1365-2265.1995.tb01857.x.
The increasing use in clinical practice of octreotide (a somatostatin analogue which inhibits the secretion of GH and other peptide hormones) led us to study the effects of this treatment on GH, insulin-like growth factors (IGF)-I and II and IGF-binding protein (IGFBP)-3, as well as on circulating IGFBP complexes in acromegalic patients.
The circulating concentrations of GH, IGF-I, IGF-II and IGFBP-3 were measured in acromegalic patients before and after 3, 6, 9, and 12 months of treatment with octreotide (group I: n = 5), and compared with those found in a group of patients (group II) treated with bromocriptine (n = 3), cabergoline (n = 7) radiotherapy (n = 3) or surgical therapy (n = 2). In pools of serum obtained from patients treated with octreotide, dopaminergic drugs, surgery and radiation, before and after therapy, immunoreactive IGF-I and IGFBP-3 were also evaluated after Superdex 200 gel filtration in neutral conditions.
Before treatment, the concentration of IGF-I and IGFBP-3 were above the normal range in all patients, while IGF-II levels were slightly reduced. After treatment with octreotide, IGF-I (P = 0.004), IGF-II (P = 0.02) and IGFBP-3 (P < 0.001) were significantly reduced as compared to basal levels. In subjects of group II, only IGF-I concentration was significantly reduced by the treatment (P = 0.02), and a negative correlation between IGF-I and IGF-II concentrations was found (r = -0.58, P < 0.0001). After gel filtration immunoreactive IGF-I and IGFBP-3 were found in the 150-kDa mol.wt. region in serum obtained from untreated patients and from treated patients of group II, while in the serum of octreotide-treated patients the IGF-I and IGFBP-3 peaks were shifted to the 60-kDa mol.wt. region, thus suggesting that the acid-labile subunit of the 150-kDa complex was drastically reduced. Since the GH concentrations in groups I and II were similar (M +/- SEM; 13.8 +/- 7.4 and 21.2 +/- 10.6 mU/l respectively), the marked reduction in acid-labile subunit in the octreotide treated patients can be explained by a direct inhibitory effect of somatostatin on the subunit.
Octreotide exerts an inhibitory effect not only on IGF-I but also on IGF-II. The reduced formation of the 150-kDa complex probably causes an increased metabolic clearance rate of IGF peptides which can account for the reduced concentration of both IGFs after treatment with octreotide.
奥曲肽（一种抑制生长激素及其他肽类激素分泌的生长抑素类似物）在临床实践中的应用日益增加，这促使我们研究该治疗方法对肢端肥大症患者生长激素、胰岛素样生长因子（IGF）-Ⅰ和Ⅱ、IGF结合蛋白（IGFBP）-3以及循环IGFBP复合物的影响。
测定肢端肥大症患者在接受奥曲肽治疗3、6、9和12个月之前及之后的生长激素、IGF-Ⅰ、IGF-Ⅱ和IGFBP-3的循环浓度（第一组：n = 5），并与接受溴隐亭（n = 3）、卡麦角林（n = 7）、放射治疗（n = 3）或手术治疗（n = 2）的一组患者（第二组）的测定结果进行比较。在奥曲肽治疗患者、多巴胺能药物治疗患者、手术治疗患者和放射治疗患者治疗前后的血清样本中，于中性条件下经Superdex 200凝胶过滤后，还对免疫反应性IGF-Ⅰ和IGFBP-3进行了评估。
治疗前，所有患者的IGF-Ⅰ和IGFBP-3浓度均高于正常范围，而IGF-Ⅱ水平略有降低。奥曲肽治疗后，与基础水平相比，IGF-Ⅰ（P = 0.004）、IGF-Ⅱ（P = 0.02）和IGFBP-3（P < 0.001）显著降低。在第二组患者中，仅IGF-Ⅰ浓度因治疗而显著降低（P = 0.02），且发现IGF-Ⅰ与IGF-Ⅱ浓度之间存在负相关（r = -0.58，P < 0.0001）。凝胶过滤后，在未治疗患者及第二组治疗患者的血清中，免疫反应性IGF-Ⅰ和IGFBP-3出现在150-kDa分子量区域，而在奥曲肽治疗患者的血清中，IGF-Ⅰ和IGFBP-3峰转移至60-kDa分子量区域，这表明150-kDa复合物的酸不稳定亚基大幅减少。由于第一组和第二组的生长激素浓度相似（M +/- SEM；分别为13.8 +/- 7.4和21.2 +/- 10.6 mU/l），奥曲肽治疗患者中酸不稳定亚基的显著减少可通过生长抑素对该亚基的直接抑制作用来解释。
奥曲肽不仅对IGF-Ⅰ有抑制作用，对IGF-Ⅱ也有抑制作用。150-kDa复合物形成减少可能导致IGF肽的代谢清除率增加，这可以解释奥曲肽治疗后两种IGF浓度降低的原因。
