Marcilhac A, Dakine N, Bourhim N, Guillaume V, Grino M, Drieu K, Oliver C
Laboratoire de Neuroendocrinologie Expérimentale, INSERM U 297, Institut Jean Roche, Faculté de Médecine Secteur Nord, Marseille, France.
Life Sci. 1998;62(25):2329-40. doi: 10.1016/s0024-3205(98)00214-8.
The hypersecretion of glucocorticoids during exposure to various stressors may induce or worsen pathological states in predisposed subjects. Therefore it is of interest to evaluate drugs able to reduce glucocorticoid secretion. It has recently been shown that chronic administration of a Ginkgo biloba extract (EGb 761) inhibits stress-induced corticosterone hypersecretion through a reduction in the number of adrenal peripheral benzodiazepine receptors. The present study was designed to analyze the effect of EGb 761 and one of its components, Ginkgolide B on the biosynthesis and secretion of CRH and AVP, the hypothalamic neurohormones that regulate the pituitary-adrenal axis. Chronic administration of EGb 761 (50 or 100 mg/kg p.o. daily for 14 days) reduced basal corticosterone secretion and the subsequent increase in CRH and AVP gene expression. Under the same conditions, surgically-induced increase in CRH secretion was attenuated while the activation of CRH gene expression, ACTH and corticosterone secretion following insulin-induced hypoglycemia remained unchanged. Chronic i.p. injection of Ginkgolide B reduced basal corticosterone secretion without alteration in the subsequent CRH and AVP increase. However, the stimulation of CRH gene expression by insulin-induced hypoglycemia was attenuated by Ginkgolide B. These data confirm that the administration of EGb 761 and Ginkgolide B reduces corticosterone secretion. In addition, these substances act also at the hypothalamic level and are able to reduce CRH expression and secretion. However the latter effect appears to be complex and may depend upon both the nature of stress and substance (Ginkgolide B or other compounds of EGb 761).
在暴露于各种应激源期间，糖皮质激素分泌过多可能会在易感个体中诱发或加重病理状态。因此，评估能够减少糖皮质激素分泌的药物具有重要意义。最近的研究表明，长期给予银杏叶提取物（EGb 761）可通过减少肾上腺外周苯二氮䓬受体的数量来抑制应激诱导的皮质酮分泌过多。本研究旨在分析EGb 761及其成分之一银杏内酯B对促肾上腺皮质激素释放激素（CRH）和精氨酸加压素（AVP）的生物合成和分泌的影响，这两种下丘脑神经激素调节垂体 - 肾上腺轴。长期给予EGb 761（50或100mg/kg口服，每日14天）可降低基础皮质酮分泌以及随后CRH和AVP基因表达的增加。在相同条件下，手术诱导的CRH分泌增加减弱，而胰岛素诱导的低血糖后CRH基因表达、促肾上腺皮质激素（ACTH）和皮质酮分泌的激活保持不变。长期腹腔注射银杏内酯B可降低基础皮质酮分泌，而随后的CRH和AVP增加没有改变。然而，银杏内酯B可减弱胰岛素诱导的低血糖对CRH基因表达的刺激。这些数据证实，给予EGb 761和银杏内酯B可降低皮质酮分泌。此外，这些物质也作用于下丘脑水平，能够减少CRH的表达和分泌。然而，后一种作用似乎很复杂，可能取决于应激的性质和物质（银杏内酯B或EGb 761的其他化合物）。
