Krsmanovic L Z, Martinez-Fuentes A J, Arora K K, Mores N, Tomić M, Stojilkovic S S, Catt K J
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4510, USA.
Endocrinology. 2000 Mar;141(3):1187-95. doi: 10.1210/endo.141.3.7392.
Cultured rat pituitary cells and immortalized pituitary gonadotrophs (alphaT3-1 cells) express specific messenger RNA transcripts for GnRH and exhibit positive immunostaining for the GnRH peptide. Each cell type released GnRH during both static culture and perifusion, albeit in lesser amounts than cultured hypothalamic cells and GT1-7 neurons. In perifused pituitary cells, exposure to a GnRH agonist stimulated the release of GnRH as well as LH. In contrast, treatment with a GnRH receptor antagonist or with GnRH antiserum decreased basal LH release. In pituitary cell cultures, a small proportion of gonadotrophs exhibited high amplitude and low frequency baseline Ca2+ oscillations in the absence of GnRH stimulation. Such spontaneous oscillations were comparable to those induced by picomolar concentrations of GnRH and could be abolished by treatment with a GnRH antagonist. These in vitro findings indicate that locally produced GnRH causes low level activation of pituitary GnRH receptors, induces spontaneous intracellular Ca2+ oscillations, and contributes to basal LH secretion in cultured pituitary cells. In vivo, such autocrine or paracrine actions of pituitary-derived GnRH could provide a mechanism for the maintenance of optimal responsiveness of the gonadotrophs to pulses of GnRH arising in the hypothalamus. The presence and actions of GnRH in the anterior pituitary gland, the major site of expression of GnRH receptors, suggest that local regulatory effects of the neuropeptide could supplement the primary hypothalamic mechanism for the control of episodic gonadotropin secretion.
培养的大鼠垂体细胞和永生化垂体促性腺激素细胞（αT3-1细胞）表达促性腺激素释放激素（GnRH）的特定信使核糖核酸转录本，并对GnRH肽呈阳性免疫染色。在静态培养和灌流过程中，每种细胞类型都会释放GnRH，尽管释放量少于培养的下丘脑细胞和GT1-7神经元。在灌流的垂体细胞中，暴露于GnRH激动剂会刺激GnRH以及促黄体生成素（LH）的释放。相反，用GnRH受体拮抗剂或GnRH抗血清处理会降低基础LH释放。在垂体细胞培养物中，一小部分促性腺激素细胞在没有GnRH刺激的情况下表现出高幅度和低频率的基线钙离子（Ca2+）振荡。这种自发振荡与皮摩尔浓度的GnRH诱导的振荡相当，并且可以通过用GnRH拮抗剂处理而消除。这些体外研究结果表明，局部产生的GnRH会导致垂体GnRH受体的低水平激活，诱导细胞内自发的Ca2+振荡，并有助于培养的垂体细胞中基础LH的分泌。在体内，垂体来源的GnRH的这种自分泌或旁分泌作用可能为维持促性腺激素细胞对下丘脑产生的GnRH脉冲的最佳反应性提供一种机制。GnRH在垂体前叶（GnRH受体表达的主要部位）的存在和作用表明，这种神经肽的局部调节作用可以补充下丘脑控制促性腺激素间歇性分泌的主要机制。
