Devesa J, Barros M G, Gondar M, Tresguerres J A, Arce V
Department of Physiology, School of Medicine, University of Santiago de Compostela, Spain.
J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):277-82. doi: 10.1016/0960-0760(95)00065-8.
Glucocorticoids (GCs) play a key role in the physiology of the hypothalamic-somatotroph axis, since these steroids enhance growth hormone (GH) gene transcription and increase GHRH receptor synthesis. However, GC excess inhibits normal growth in all species studied. This is mainly due to the impaired GH secretion observed during hypercortisolism, a situation in which GH responses to a number of stimuli, including GHRH, are blunted. The inhibitory effect of GCs on GH secretion seems to be dependent on enhanced hypothalamic SS secretion. Since SS release is stimulated by beta-adrenergic agonism we tested the possibility that GC inhibition of GH secretion would depend on increased beta-adrenoceptor activity in SS-producing neurons. The experimental design consisted in evaluating the GH response to GHRH in normal subjects after having induced hypercortisolism, with DEX, and blocking beta-adrenoceptors with propranolol (PRO). Moreover, to investigate the specificity of this mechanism, GHRH-induced GH release was tested after inducing hypercortisolism and enhancing alpha 2-adrenergic or muscarinic cholinergic tone, by giving clonidine (CLO) or pyridostigmine (PD), respectively. As expected, nocturnal DEX administration inhibited the GH response to GHRH. In this situation of hypercortisolism, both PRO and CLO, but not PD, were able to reverse the inhibitory effect of DEX on GHRH-elicited release. However, the potentiating effect of these drugs on the GHRH-induced GH secretion was only observed for PRO. These data confirm that GC excess inhibits GH release by increasing hypothalamic SS secretion, and that the mechanism is mediated by GC-induced enhanced beta-adrenergic responsiveness. Therefore, the defective GHRH secretion observed in chronic hypercortisolism must be a consequence of the continuous blockade that SS excess exerts on GHRH-producing neurons. Our postulate agrees with other data in the literature showing that GCs modulate the secretion of some hypothalamic peptides by changing the responsiveness of the producing neurons from alpha 2-adrenoceptors to that of beta-adrenoceptors.
糖皮质激素（GCs）在下丘脑-生长激素细胞轴的生理过程中起关键作用，因为这些类固醇可增强生长激素（GH）基因转录并增加生长激素释放激素（GHRH）受体合成。然而，GCs过量会抑制所有已研究物种的正常生长。这主要是由于在皮质醇增多症期间观察到GH分泌受损，在这种情况下，GH对包括GHRH在内的多种刺激的反应减弱。GCs对GH分泌的抑制作用似乎取决于下丘脑促甲状腺素释放激素（SS）分泌的增加。由于β-肾上腺素能激动作用可刺激SS释放，我们测试了GCs抑制GH分泌是否取决于SS分泌神经元中β-肾上腺素能受体活性增加的可能性。实验设计包括在通过地塞米松（DEX）诱导皮质醇增多症后，评估正常受试者对GHRH的GH反应，并用普萘洛尔（PRO）阻断β-肾上腺素能受体。此外，为了研究这种机制的特异性，在分别给予可乐定（CLO）或吡啶斯的明（PD）诱导皮质醇增多症并增强α2-肾上腺素能或毒蕈碱胆碱能张力后，测试GHRH诱导的GH释放。正如预期的那样，夜间给予DEX会抑制GH对GHRH的反应。在这种皮质醇增多症的情况下，PRO和CLO都能够逆转DEX对GHRH诱导释放的抑制作用，但PD不能。然而，这些药物对GHRH诱导的GH分泌的增强作用仅在PRO中观察到。这些数据证实，GCs过量通过增加下丘脑SS分泌来抑制GH释放，并且该机制由GCs诱导的增强的β-肾上腺素能反应性介导。因此，在慢性皮质醇增多症中观察到的GHRH分泌缺陷必定是SS过量对产生GHRH的神经元持续阻断的结果。我们的假设与文献中的其他数据一致，这些数据表明GCs通过改变产生神经元从α2-肾上腺素能受体到β-肾上腺素能受体的反应性来调节某些下丘脑肽的分泌。
