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甘丙肽对培养的生长激素分泌性腺瘤细胞中生长激素(GH)释放的抑制作用:与奥曲肽、生长激素释放激素及促甲状腺激素释放激素的比较研究

Inhibitory effects of galanin on growth hormone (GH) release in cultured GH-secreting adenoma cells: comparative study with octreotide, GH-releasing hormone, and thyrotropin-releasing hormone.

作者信息

Giustina A, Ragni G, Bollati A, Cozzi R, Licini M, Poiesi C, Turazzi S, Bonfanti C

机构信息

Department of Internal Medicine, University of Brescia, Italy.

出版信息

Metabolism. 1997 Apr;46(4):425-30. doi: 10.1016/s0026-0495(97)90060-3.

Abstract

The aim of the present study was to characterize in a large series (N = 12) of cultured somatotrope adenomas the in vitro effects of the neuropeptide galanin on growth hormone (GH) secretion. This was contrasted with two peptides known to be GH secretagogues (GH-releasing hormone [GHRH] and thyrotropin-releasing hormone [TRH]) and a peptide with a known GH-inhibitory effect (the somatostatin analog octreotide). Groups of three wells were incubated for 4 hours with growth medium alone (control incubation), galanin, GHRH(1-29)NH2, TRH, or octreotide. Galanin and octreotide were applied at concentrations of 0.1, 1, and 10 mumol/L, and GHRH and TRH at concentrations of 0.01, 0.1, and 1 mumol/L. Galanin was able to inhibit GH release in nine of 12 cultured somatotrope adenoma cells. This inhibitory effect was clearly dose-dependent in five adenomas. Overall, the mean GH nadir after galanin was -36.1% in nine responder adenoma cultures versus control wells. Octreotide inhibited GH release in five of eight cultured somatotrope adenoma cells. The mean GH nadir after octreotide was -32.7% in five responder adenoma cultures compared with control wells. GHRH and TRH were able to stimulate GH release, respectively, in seven of 11 and in six of seven cultured somatotrope adenoma cells. The mean GH peaks after either GHRH or TRH in responder adenoma cultures were, respectively, +71.5% and +143.7% compared with levels in the control wells. In conclusion, the consistency and potency of the in vitro GH-inhibitory effect of galanin in a large series of somatotrope adenomas are at least similar to those of the most effective available GH-lowering agent, the somatostatin analog octreotide.

摘要

本研究的目的是在一大组(N = 12)培养的生长激素腺瘤中,表征神经肽甘丙肽对生长激素(GH)分泌的体外作用。将其与两种已知的生长激素促分泌素(生长激素释放激素[GHRH]和促甲状腺激素释放激素[TRH])以及一种已知具有生长激素抑制作用的肽(生长抑素类似物奥曲肽)进行对比。将每组三个孔分别用单纯生长培养基(对照孵育)、甘丙肽、GHRH(1 - 29)NH2、TRH或奥曲肽孵育4小时。甘丙肽和奥曲肽的应用浓度分别为0.1、1和10 μmol/L,GHRH和TRH的应用浓度分别为0.01、0.1和1 μmol/L。甘丙肽能够抑制12个培养的生长激素腺瘤细胞中的9个细胞释放GH。在5个腺瘤中,这种抑制作用明显呈剂量依赖性。总体而言,在9个有反应的腺瘤培养物中,甘丙肽作用后的平均GH最低点相对于对照孔为-36.1%。奥曲肽抑制了8个培养的生长激素腺瘤细胞中的5个细胞释放GH。在5个有反应的腺瘤培养物中,奥曲肽作用后的平均GH最低点相对于对照孔为-32.7%。GHRH和TRH分别能够刺激11个培养的生长激素腺瘤细胞中的7个细胞和7个细胞中的6个细胞释放GH。在有反应的腺瘤培养物中,GHRH或TRH作用后的平均GH峰值相对于对照孔水平分别为+71.5%和+143.7%。总之,在一大组生长激素腺瘤中,甘丙肽体外抑制GH作用的一致性和效力至少与最有效的现有降低GH药物——生长抑素类似物奥曲肽相似。

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