This study was intended to demonstrate that prenatal dexamethasone exposure (PDE) can induce low basal activity of the hypothalamic-pituitary-adrenal axis (HPAA) in male offspring rats and explore the underlying mechanism. Pregnant rats were subcutaneously administered 0.2 mg/kg/d dexamethasone from gestational day (GD) 9 to GD20. Male GD20 fetuses and postnatal day 85 adult male offspring rats were sacrificed under anesthesia. Hypothalamic cells were from GD20∼postnatal day (PD) 7 fetal male rats, treated with different concentrations of dexamethasone and the glucocorticoid receptor (GR) antagonist mifepristone for 5 days. The results suggested that dexamethasone enhanced the expression of hypothalamic L-glutamic acid decarboxylase (GAD) 67 by activating GR, further stimulating the conversion of glutamate to gamma-aminobutyric acid (GABA) and inducing an imbalance in glutamatergic/GABAergic afferents in the hypothalamic paraventricular nucleus (PVN). This imbalance change was maintained postnatally, leading to the inhibition of parvocellular neurons, and mediating the low basal activity of the HPAA in PDE offspring rats, which was manifested by decreased levels of blood adrenocorticotropic hormone and corticosterone as well as reduced expression levels of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) in the hypothalamus. Programming of a developmental imbalance in glutamatergic/GABAergic afferents in the PVN is a potential mechanism responsible for low basal activity of the HPAA in male PDE rats.

中文翻译：

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下丘脑谷氨酸能/GABA能传入中发育失衡的程序化介导了雄性后代大鼠产前地塞米松暴露诱导的下丘脑-垂体-肾上腺轴的低基础活性

本研究旨在证明产前地塞米松暴露 (PDE) 可导致雄性后代大鼠下丘脑-垂体-肾上腺轴 (HPAA) 的基础活性降低，并探讨其潜在机制。从妊娠第 9 天到第 20 天，对怀孕大鼠皮下注射 0.2 mg/kg/d 地塞米松。在麻醉下处死雄性 GD20 胎儿和出生后第 85 天成年雄性后代大鼠。下丘脑细胞来自GD20～产后第7天（PD）雄性胎鼠，用不同浓度的地塞米松和糖皮质激素受体（GR）拮抗剂米非司酮处理5天。结果表明，地塞米松通过激活 GR 增强了下丘脑 L-谷氨酸脱羧酶 (GAD) 67 的表达，进一步刺激谷氨酸转化为 γ-氨基丁酸 (GABA) 并导致下丘脑室旁核 (PVN) 中谷氨酸能/GABA 能传入的不平衡。这种不平衡的变化在出生后得到维持，导致小细胞神经元受到抑制，并介导了 PDE 后代大鼠 HPAA 的低基础活性，表现为血液促肾上腺皮质激素和皮质酮水平降低以及促肾上腺皮质激素的表达水平降低。下丘脑释放激素（CRH）和精氨酸加压素（AVP）。PVN 中谷氨酸能/GABA 能传入神经发育失衡的编程是导致雄性 PDE 大鼠 HPAA 基础活性低的潜在机制。