Regulational Effect of Ghrelin on Growth Hormone Secretion from Perifused Rat Anterior Pituitary Cells
Regulational Effect of Ghrelin on Growth Hormone Secretion from Perifused Rat Anterior Pituitary Cells
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DOI：
10.1046/j.0007-1331.2001.00757.x
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发表时间：
2002-02
影响因子：
3.2
通讯作者：
Mami Yamazaki;Kazuaki Nakamura;Hiroaki Kobayashi;Maki Matsubara;Y. Hayashi;Kenji Kangawa;Takafumi Sakai
中科院分区：
文献类型：
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作者：
Mami Yamazaki;Kazuaki Nakamura;Hiroaki Kobayashi;Maki Matsubara;Y. Hayashi;Kenji Kangawa;Takafumi Sakai
Ghrelin是一种新的生长激素（GH）释放肽，最近从大鼠胃中分离出来，作为生长激素促分泌受体（GHS‐R）的内源性配体。Ghrelin可以特异性地刺激大鼠垂体前叶释放生长激素，但Ghrelin对生长激素分泌的调节作用尚未明确。我们使用灌注系统研究了生长素与生长激素释放激素（GHRH）和生长抑素对大鼠垂体前叶细胞生长激素分泌的单一作用和联合作用。ghrelin刺激引起的生长激素浓度的增加显示出一个短暂的峰值，与之前报道的GHS几乎相同，但与GHRH明显不同。Ghrelin（10−10 M ~ 10−8 M）刺激大鼠垂体前叶细胞分泌GH呈剂量依赖性。每隔1 h对分散的细胞进行连续的胃饥饿素刺激会降低生长激素的反应，但每隔3 h刺激后，生长激素的反应就会恢复，这表明胃饥饿素对细胞有强烈的脱敏作用。ghrelin和GHRH的共刺激既没有引起大鼠垂体细胞的增效反应，也没有引起加性生长激素反应。此外，用生长抑素预处理垂体前叶细胞，可以强烈地消除饥饿素和/或GHRH刺激的GH分泌。在本研究中，我们证明了ghrelin引起的GH分泌比GHRH引起的GH分泌弱，并且我们还表明GHRH的共刺激对GH分泌没有附加或协同作用，这表明ghrelin间接影响垂体的协调GH释放，正如在体内发现的那样。
Ghrelin, a novel growth hormone (GH)‐releasing peptide, was recently isolated from the rat stomach as an endogenous ligand to growth hormone secretagogue receptor (GHS‐R). Ghrelin specifically stimulates the release of GH from the rat anterior pituitary gland, but the regulational effect of ghrelin on GH secretion has not yet been clarified. We used a perifusion system to examine the single effect and combined effects of ghrelin with growth hormone‐releasing hormone (GHRH) and somatostatin on GH secretion from rat anterior pituitary cells. The increase in GH concentration due to ghrelin stimulation showed a transitory peak that was almost the same as that previously reported for GHS, but apparently distinct from that of GHRH. Ghrelin (10−10 M to 10−8 M) stimulated GH secretion from the rat anterior pituitary cells in a dose‐dependent manner. Serial ghrelin stimulation of the dispersed cells at 1‐h intervals decreased the GH response, but the response recovered with stimulation at 3‐h intervals, indicating that ghrelin strongly desensitized cells. Costimulation with ghrelin and GHRH elicited neither a synergistic nor an additive GH response from the rat pituitary cells. Furthermore, pretreatment to anterior pituitary cells with somatostatin strongly abolished ghrelin‐ and/or GHRH‐stimulated GH secretion. In this study, we demonstrated that ghrelin caused weaker GH secretion than that caused by GHRH, and we also showed that costimulation with GHRH had no additive or synergistic effect on GH secretion, suggesting that ghrelin indirectly affects coordinated GH release from pituitary gland, as found in vivo.