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下丘脑肽调节人无功能垂体腺瘤中的胞质游离Ca2+水平和腺苷酸环化酶活性。

Hypothalamic peptides modulate cytosolic free Ca2+ levels and adenylyl cyclase activity in human nonfunctioning pituitary adenomas.

作者信息

Spada A, Reza-Elahi F, Lania A, Gil-del-Alamo P, Bassetti M, Faglia G

机构信息

Institute of Endocrine Sciences, Ospedale Maggiore IRCCS, Milan, Italy.

出版信息

J Clin Endocrinol Metab. 1991 Oct;73(4):913-8. doi: 10.1210/jcem-73-4-913.

DOI:10.1210/jcem-73-4-913
PMID:1679762
Abstract

The effects of hypothalamic peptides (TRH, GnRH, arginine vasopressin, vasoactive intestinal peptide, GHRH, CRH, and SRIH) on cytosolic free calcium concentrations ([Ca2+]i) and adenylyl cyclase (AC) activity were evaluated in 12 nonfunctioning pituitary adenomas. TRH, GnRH, and arginine vasopressin induced a marked [Ca2+]i rise in 10/12, 4/12, and 2/5 tumors, respectively. The transients induced by these peptides were due to both Ca2+ mobilization from the intracellular stores and Ca2+ influx from the extracellular medium. AC activity was evaluated in 10 adenomas; 1 microM vasoactive intestinal peptide induced a 2- to 6-fold stimulation of the enzyme activity in all tumors, while neither GHRH nor CRH were effective. Moreover, in 5/10 tumors 1 microM SRIH reduced both AC activity and [Ca2+]i, while in 2/10 the peptide caused a significant rise in [Ca2+]i despite the AC inhibition and in 3/10 SRIH did not modify either AC activity or [Ca2+]i. This study indicates that in nonfunctioning pituitary adenomas a wide spectrum of hypothalamic peptides modulate [Ca2+]i and AC activity. Moreover, the presence of biologically active receptors may offer a possible target for therapeutic intervention.

摘要

在12例无功能垂体腺瘤中评估了下丘脑肽(促甲状腺激素释放激素、促性腺激素释放激素、精氨酸加压素、血管活性肠肽、生长激素释放激素、促肾上腺皮质激素释放激素和生长抑素)对胞浆游离钙浓度([Ca2+]i)和腺苷酸环化酶(AC)活性的影响。促甲状腺激素释放激素、促性腺激素释放激素和精氨酸加压素分别在10/12、4/12和2/5的肿瘤中诱导了显著的[Ca2+]i升高。这些肽诱导的瞬变是由于细胞内储存的Ca2+动员和细胞外介质的Ca2+内流。在10例腺瘤中评估了AC活性;1μM血管活性肠肽在所有肿瘤中诱导了该酶活性2至6倍的刺激,而生长激素释放激素和促肾上腺皮质激素释放激素均无效。此外,在5/10的肿瘤中,1μM生长抑素降低了AC活性和[Ca2+]i,而在2/10的肿瘤中,尽管AC受到抑制,但该肽导致[Ca2+]i显著升高,在3/10的肿瘤中,生长抑素既未改变AC活性也未改变[Ca2+]i。这项研究表明,在无功能垂体腺瘤中,多种下丘脑肽调节[Ca2+]i和AC活性。此外,生物活性受体的存在可能为治疗干预提供一个可能的靶点。

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Gonadotropin-releasing hormone initiates multiple signaling pathways in human GH-secreting adenomas.促性腺激素释放激素在人生长激素分泌性腺瘤中启动多种信号通路。
J Endocrinol Invest. 2004 Apr;27(4):328-33. doi: 10.1007/BF03351057.
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Genesis of pituitary adenomas: state of the art.垂体腺瘤的起源:当前进展
J Neurooncol. 2001 Sep;54(2):95-110. doi: 10.1023/a:1012988828164.
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