Wong Anderson O L, Chuk Maggie C Y, Chan Hiu Chi, Lee Eric K Y
Dept. of Zoology, Univ. of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
Am J Physiol Endocrinol Metab. 2007 Jan;292(1):E203-14. doi: 10.1152/ajpendo.00337.2006. Epub 2006 Aug 29.
In the goldfish, norepinephrine (NE) inhibits growth hormone (GH) secretion through activation of pituitary alpha(2)-adrenergic receptors. Interestingly, a GH rebound is observed after NE withdrawal, which can be markedly enhanced by prior exposure to gonadotropin-releasing hormone (GnRH). Here we examined the mechanisms responsible for GnRH potentiation of this "postinhibition" GH rebound. In goldfish pituitary cells, alpha(2)-adrenergic stimulation suppressed both basal and GnRH-induced GH mRNA expression, suggesting that a rise in GH synthesis induced by GnRH did not contribute to its potentiating effect. Using a column perifusion approach, GnRH given during NE treatment consistently enhanced the GH rebound following NE withdrawal. This potentiating effect was mimicked by activation of PKC and adenylate cyclase (AC) but not by induction of Ca(2+) entry through voltage-sensitive Ca(2+) channels (VSCC). Furthermore, GnRH-potentiated GH rebound could be alleviated by inactivation of PKC, removal of extracellular Ca(2+), blockade of VSCC, and inhibition of Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII). Inactivation of AC and PKA, however, was not effective in this regard. These results, as a whole, suggest that GnRH potentiation of GH rebound following NE inhibition is mediated by PKC coupled to Ca(2+) entry through VSCC and subsequent activation of CaMKII. Apparently, the Ca(2+)-dependent cascades are involved in GH secretion during the rebound phase but are not essential for the initiation of GnRH potentiation. Since GnRH has been previously shown to have no effects on cAMP synthesis in goldfish pituitary cells, the involvement of cAMP-dependent mechanisms in GnRH potentiation is rather unlikely.
在金鱼中，去甲肾上腺素（NE）通过激活垂体α₂ - 肾上腺素能受体来抑制生长激素（GH）的分泌。有趣的是，在NE撤除后会观察到GH的反弹，而预先暴露于促性腺激素释放激素（GnRH）可显著增强这种反弹。在此，我们研究了GnRH增强这种“抑制后”GH反弹的机制。在金鱼垂体细胞中，α₂ - 肾上腺素能刺激抑制了基础和GnRH诱导的GH mRNA表达，这表明GnRH诱导的GH合成增加对其增强作用没有贡献。采用柱式灌流方法，在NE处理期间给予GnRH始终能增强NE撤除后的GH反弹。这种增强作用可通过激活蛋白激酶C（PKC）和腺苷酸环化酶（AC）来模拟，但通过电压敏感性钙通道（VSCC）诱导Ca²⁺内流则不能模拟。此外，PKC失活、去除细胞外Ca²⁺、阻断VSCC以及抑制Ca²⁺/钙调蛋白（CaM）依赖性蛋白激酶II（CaMKII）均可减轻GnRH增强的GH反弹。然而，AC和蛋白激酶A（PKA）失活在这方面无效。总体而言，这些结果表明，NE抑制后GnRH对GH反弹的增强作用是由与通过VSCC的Ca²⁺内流偶联的PKC以及随后CaMKII的激活介导的。显然，Ca²⁺依赖性级联反应参与了反弹期的GH分泌，但对于GnRH增强作用的起始并非必不可少。由于先前已表明GnRH对金鱼垂体细胞中的cAMP合成没有影响，因此cAMP依赖性机制参与GnRH增强作用的可能性较小。
