Givalois L, Li S, Pelletier G
Molecular Endocrinology Laboratory, CHUL Research Center of Laval University, Québec, Canada.
Neuroendocrinology. 1998 Aug;68(2):98-104. doi: 10.1159/000054355.
We have recently demonstrated that the endozepine octadecaneuropeptide (ODN) exerts an inhibitory influence on corticotropin-releasing hormone (CRH) mRNA expression. The effect is mediated by GABAA receptors and is reversed by adrenalectomy. In order to investigate the involvement of peripheral steroids and more particularly of glucocorticoids in the ODN modulation of CRH mRNA expression, we have evaluated, in adrenalectomized and castrated male rats (ADX/CX), the effect of dexamethasone (DEX) pretreatment on CRH mRNA expression induced by central injection of ODN. Variations in the CRH mRNA expression in the hypothalamic paraventricular nucleus have been studied using quantitative in situ hybridization. The intracerebroventricular injection of ODN (4 microg/kg), as previously reported, induced a significant inhibition of CRH mRNA expression in sham-operated rats (-33%). This inhibition was reversed in ADX/CX male rats (+65% vs. sham vehicle-injected rats and +20% vs. ADX/CX vehicle-injected rats). Pretreatment with DEX (5 mg/kg) during 4 days induced in ADX/CX rats a decrease of 22% (vs. ADX/CX vehicle-injected rats) in the CRH mRNA signal, which became comparable to that observed in sham vehicle-injected rats. Pretreatment of ADX/CX animals with DEX prevented the ODN-induced increase in CRH mRNA expression, inducing rather a 16 and 30% inhibition when compared to vehicle- and ODN-injected ADX/CX rats, respectively. Moreover the CRH mRNA levels observed in ODN-injected ADC/CX rats were higher than those observed in sham vehicle- and sham ODN-injected rats (+16% vs. sham vehicle-injected rats and +63% vs. sham ODN-injected rats). These results indicate that dexamethasone treatment in ADX/CX rats can restore mRNA levels to those observed in sham-operated animals but not the inhibiting effect induced by ODN. Together with previous findings, these results suggest that adrenal and/or gonadal factor(s) other than glucocorticoids are involved in ODN modulation of the HPA axis.
我们最近证实，内源性阿片肽十八烷神经肽（ODN）对促肾上腺皮质激素释放激素（CRH）的mRNA表达具有抑制作用。该作用由GABAA受体介导，且肾上腺切除可逆转此作用。为了研究外周类固醇尤其是糖皮质激素在ODN对CRH mRNA表达调节中的作用，我们评估了在肾上腺切除和去势的雄性大鼠（ADX/CX）中，地塞米松（DEX）预处理对中枢注射ODN诱导的CRH mRNA表达的影响。使用定量原位杂交技术研究了下丘脑室旁核中CRH mRNA表达的变化。如先前报道，脑室内注射ODN（4微克/千克）可在假手术大鼠中显著抑制CRH mRNA表达（-33%）。在ADX/CX雄性大鼠中，这种抑制作用被逆转（与假手术组注射溶剂的大鼠相比增加65%，与ADX/CX组注射溶剂的大鼠相比增加20%）。在ADX/CX大鼠中，连续4天用DEX（5毫克/千克）预处理可使CRH mRNA信号降低22%（与ADX/CX组注射溶剂的大鼠相比），这与假手术组注射溶剂的大鼠中观察到的信号相当。用DEX预处理ADX/CX动物可防止ODN诱导的CRH mRNA表达增加，与注射溶剂和ODN的ADX/CX大鼠相比，分别产生16%和30%的抑制作用。此外，在注射ODN的ADC/CX大鼠中观察到的CRH mRNA水平高于假手术组注射溶剂和假手术组注射ODN的大鼠（与假手术组注射溶剂的大鼠相比增加16%，与假手术组注射ODN的大鼠相比增加63%）。这些结果表明，在ADX/CX大鼠中，地塞米松治疗可使mRNA水平恢复到假手术动物中观察到的水平，但不能恢复ODN诱导的抑制作用。与先前的研究结果一起，这些结果表明除糖皮质激素外，肾上腺和/或性腺因子参与了ODN对下丘脑-垂体-肾上腺轴的调节。
