Secretory mechanisms of growth hormone (GH)-releasing peptide-, GH-releasing hormone-, and thyrotropin-releasing hormone-induced GH release in patients with acromegaly.

Secretory mechanisms of growth hormone (GH)-releasing peptide-, GH-releasing hormone-, and thyrotropin-releasing hormone-induced GH release in patients with acromegaly.
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肢端肥大症患者生长激素(GH)释放肽、GH释放激素和促甲状腺激素释放激素诱导的 GH 释放的分泌机制。

DOI:
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发表时间:
1998
影响因子:
5.8
通讯作者:
Yutaka Yokogoshi
Yutaka Yokogoshi
中科院分区:
医学2区
文献类型:
--
作者:
Kunihiko Hanew;Atushi Utsumi;A. Tanaka;H. Ikeda;Yutaka Yokogoshi

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本文对7例肢端肥大症患者的生长激素释放六肽(GHRP-6)、生长激素释放激素(GHRH)和促性腺激素释放激素(TRH)的分泌机制进行了体内外研究。在一项活体研究中,这些患者对单独使用GHRP(4名患者)、GHRH(7名患者)和TRH(7名患者)表现出明显的GH反应,而对GHRP+GHRH(2名患者)或TRH+GHRH(6名患者)的反应增强。在体外分散细胞研究中,被检查的大多数患者对GHRP(4例)、GHRH(6例)和TRH(4例)也显示出明显的GH反应,而对GHRP+GHRH(3例)或TRH+GHRH(3例)的反应增强(3例)。在1例患者(3号)中,GHRP加Forsklin(腺苷环化酶激活剂),而不是GHRP加佛波酯(蛋白激酶C激活剂)可增加生长激素反应。去甲二氢愈创木酸(NDGA;花生四烯酸级联抑制剂)抑制GHRP、TRH、GHRH、TRH+GHRH或GHRP+GHRH诱导的GH释放,但不抑制基础GH的分泌。相反,当NDGA与GHRP、GHRH或GHRP与GHRH联合应用时,另一位患者(第7位)的细胞内cAMP水平明显升高,而单独应用GHRP和NDGA不能改变cAMP水平。在这名患者中,联合应用GHRP和GHRH的生长激素反应是协同的,但在另外两名患者中是相加的。结论:GHRP、TRH和GHRH在体内外均可直接刺激生长激素瘤细胞释放GH,其中GHRP和TRH主要通过激活磷脂酰肌醇-蛋白激酶C途径发挥作用,而GHRH主要通过腺苷环化酶-蛋白激酶A途径发挥作用。这三种药物似乎通过花生四烯酸的级联反应释放GH。
The GH secretory mechanism of GH-releasing hexapeptide (GHRP-6), GHRH, and TRH were studied in vivo and in vitro in seven patients with acromegaly. In an in vivo study, these patients showed clear GH responses to single administration of GHRP (four of four patients), GHRH (seven of seven patients), and TRH (seven of seven patients) and enhanced responses to GHRP plus GHRH (two of four patients) or TRH plus GHRH (six of six patients). In an in vitro dispersed cell study, the majority of patients examined also showed clear GH responses to GHRP (four of four patients), GHRH (six of six patients), and TRH (four of four patients) and an enhanced response to GHRP plus GHRH (three of three patients) or TRH plus GHRH (three of four patients). In one patient (no. 3), GHRP plus forskolin (adenylate cyclase activator), but not GHRP plus phorbol 12-myristate 13-acetate (protein kinase C activator), additively enhanced the GH response. Nordihydroguaiaretic acid (NDGA; inhibitor of arachidonic cascade) inhibited GH release induced by GHRP, TRH, GHRH, TRH plus GHRH, or GHRP plus GHRH, but did not inhibit basal GH secretion. In contrast, NDGA distinctly elevated intracellular cAMP levels in another patient (no. 7) when coadministered with GHRP, GHRH, or GHRP plus GHRH, whereas cAMP levels were not modified by single administration of GHRP and NDGA. The GH response to the combined administration of GHRP and GHRH was synergistic in this patient, but was additive in the other two patients. It is concluded that GHRP, TRH, and GHRH directly stimulate in vivo and in vitro GH release from human somatotropinomas, and GHRP and TRH mainly exert their action through activation of the phosphatidylinositol-protein kinase C pathway, whereas GHRH exerts its action through the adenylate cyclase-protein kinase A pathway. These three agents seem to release GH via the arachidonic cascade.
肢端肥大症中生长激素 (GH) 对 GH 释放肽 (His-DTrp-Ala-Trp-DPhe-Lys-NH2)、GH 释放激素和促甲状腺素释放激素的反应。
DOI: 10.1210/jcem.77.3.8370708
发表时间: 1993
期刊: The Journal of clinical endocrinology and metabolism
影响因子: --
作者:
Alster,DK;Bowers,CY;Jaffe,CA;Ho,PJ;Barkan,AL
通讯作者: Barkan,AL
DOI: 10.1210/endo-128-4-2027
发表时间: 1991-04-01
期刊: ENDOCRINOLOGY
影响因子: 4.8
作者:
BOWERS, CY;SARTOR, AO;BADGER, TM
通讯作者: BADGER, TM
口服生长激素 (GH) 释放肽可刺激正常男性的 GH 分泌。
DOI: 10.1210/jcem.74.6.1592884
发表时间: 1992
期刊: The Journal of clinical endocrinology and metabolism
影响因子: --
作者:
Hartman,ML;Farello,G;Pezzoli,SS;Thorner,MO
通讯作者: Thorner,MO
DOI: 10.1016/0006-291x(82)91762-4
发表时间: 1982
影响因子: 3.1
作者:
Brazeau,P;Ling,N;Esch,F;Böhlen,P;Mougin,C;Guillemin,R
通讯作者: Guillemin,R