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肢端肥大症患者对奥曲肽的生长激素反应与腺瘤生长抑素受体状态相关。

The growth hormone responses to octreotide in acromegaly correlate with adenoma somatostatin receptor status.

作者信息

Reubi J C, Landolt A M

机构信息

Sandoz Research Institute, Berne, Switzerland.

出版信息

J Clin Endocrinol Metab. 1989 Apr;68(4):844-50. doi: 10.1210/jcem-68-4-844.

Abstract

We studied the correlation between the presence of somatostatin (SRIH) receptors in GH secreting tumors and the in vivo GH responsiveness to the SRIH analog octreotide in 11 acromegalic patients. To test in vivo octreotide (SMS 201-995) responsiveness, the patients were given a single dose (100 micrograms, sc) and their plasma GH levels were measured for several hours. Somatostatin receptor content was measured by receptor autoradiography on frozen tumor tissue sections using either a somatostatin-28 analog or a SRIH octapeptide analog (Tyr3-octreotide) as iodinated radioligands. In eight acromegalic patients, who had complete and long lasting GH inhibition after octreotide administration, SRIH receptors with high affinity for octreotide were distributed homogeneously in the tumor tissue. Two patients had moderate, short duration, and incomplete inhibition of GH secretion after octreotide administration, and their tumors had very low capacity and/or affinity SRIH receptors. A further patient who had a moderate response to octreotide had SRIH receptors that were nonhomogeneously distributed throughout the tumor. These data suggest that the therapeutic efficacy of octreotide may be related to tumor SRIH receptor levels; the best in vivo responses to octreotide occurred in patients whose tumors contained a high density of homogeneously distributed receptors which had a high affinity for octreotide.

摘要

我们研究了11例肢端肥大症患者生长激素分泌肿瘤中生长抑素(SRIH)受体的存在与体内生长激素对SRIH类似物奥曲肽反应性之间的相关性。为了检测体内奥曲肽(SMS 201-995)的反应性,给患者单次注射(皮下注射100微克),并在数小时内测量其血浆生长激素水平。使用生长抑素-28类似物或SRIH八肽类似物(Tyr3-奥曲肽)作为碘化放射性配体,通过对冷冻肿瘤组织切片进行受体放射自显影来测量生长抑素受体含量。在8例肢端肥大症患者中,奥曲肽给药后生长激素受到完全且持久的抑制,对奥曲肽具有高亲和力的SRIH受体在肿瘤组织中均匀分布。2例患者奥曲肽给药后生长激素分泌受到中度、短期且不完全的抑制,其肿瘤的SRIH受体能力和/或亲和力非常低。另有1例对奥曲肽有中度反应的患者,其SRIH受体在整个肿瘤中分布不均匀。这些数据表明,奥曲肽的治疗效果可能与肿瘤SRIH受体水平有关;对奥曲肽体内反应最佳的患者,其肿瘤含有高密度的均匀分布且对奥曲肽具有高亲和力的受体。

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