Effects of Moxibustion on Amygdala -HPA Axis in Rats with Kidney-Yang Deficiency Syndrome Induced by Hydrocortisone Injection

2020 ◽  
Author(s):  
Wen-guo Ye ◽  
Hai-hua Yao ◽  
You-jiang Min ◽  
Kai-tao Luo ◽  
Jie Sun ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Hpa Axis ◽  
Intraperitoneal Injection ◽  
Model Building ◽  
Deficiency Syndrome ◽  
Normal Group ◽  
Model Group ◽  
Suspended Moxibustion ◽  
Moxibustion Group ◽  
Protein Expressions

Abstract Background: The syndrome of kidney-yang deficiency is one of the main syndromes in traditional Chinese medicine. Modern evidences prove that the hypothalamus - pituitary - adrenal axis (HPA axis) function disorder is the main material basis of kidney-yang deficiency syndrome. The upper regulating center, such as hippocampus and amygdala can affected HPA axis. Although moxibustion have a therapeutic effect for kidney-yang deficiency syndromes, the underlying mechanism remains unclear. This study investigated the effect of suspended moxibustion on amygdala and HPA axis and elucidated the possible molecular mechanism of moxibustion in improving kidney-yang deficiency syndrome.Methods: 60 male Sprague-Dawley rats were randomly divided into the normal group ( n=12) and the model-building group (n=48). Rats in the model-building group were given intramuscular injection of hydrocortisone to establish the model of kidney-yang deficiency. The 48 rats successfully modeled were then randomly divided into model group (model, n=12) , carbenoxolone intraperitoneal injection group (CBX, n=12), moxibustion group (moxi, n=12) and moxibustion plus carbenoxolone intraperitoneal injection group (moxi+CBX, n=12). In the moxibustion group, Shenshu (BL23) and Guanyuan (CV4) points were treated with moxibustion for 14 days. After treatment, the level of corticostesone (CORT), adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in serum, the expressions of mineralocorticoid receptor (MR), glucocorticoid receptor (GR), 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1), corticotropin releasing factor (CRF) and ACTH in rats’ amygdala and (or) hypothalamus, pituitary were detected. Data were analyzed by one-way analysis of variance.Results: Compared with the normal group, the level of CRH, ACTH and CORT in serum, and the mRNA and protein expressions of MR, GR and 11β-HSD1in amygdala, the mRNA and protein expressions of 11β-HSD1 in hypothalamus and CRF mRNA expression in amygdala and hypothalamus, and ACTH mRNA expression in pituitary of rats in the model group were all significantly decreased (P < 0.05 or 0.01). After treatment with moxibustion, except for 11β-HSD1 mRNA expression, the observation index mentioned above were increased to different degrees compared with those in the model group (P < 0.05 or 0.01). Conclusion: Suspended moxibustion can effectively improve the serum levels of ACTH, CRH and CORT, and can up-regulate the mRNA and protein expression of MR, GR , 11β-HSD1, CRF and ACTH in amygdala and hypothalamus of kidney-yang deficiency rats, which may be one of the molecular mechanisms of moxibustion in improving kidney-yang deficiency syndrome.

scholarly journals Effect of moxibustion on the expression of GDNF and its receptor GFRα3 in the colon and spinal cord of rats with irritable bowel syndrome

2019 ◽  
Vol 37 (4) ◽  
pp. 244-251 ◽  
Author(s):  
Qin Qi ◽  
Huangan Wu ◽  
Xiaoming Jin ◽  
Duiyin Jin ◽  
Yuanyuan Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Irritable Bowel Syndrome ◽  
Rat Model ◽  
Normal Group ◽  
Mustard Oil ◽  
Group Model ◽  
Model Group ◽  
Moxibustion Group ◽  
Mild Moxibustion ◽  
Irritable Bowel

Background: Moxibustion treatment has been found to ameliorate clinical symptoms including abdominal pain, diarrhoea and constipation in patients with irritable bowel syndrome (IBS). Herein we investigated the mechanisms underlying the use of moxibustion in a rat model of IBS. Methods: In our study, an IBS model was established in rats by colorectal distension (CRD) stimulus and mustard oil enema. The rats were randomly divided into a normal group, model group, mild moxibustion group, electroacupuncture group, probiotic group and dicetel group. Abdominal withdrawal reflex (AWR) scores were determined within 90 min of the last treatment. The expression of GDNF/GFRα3 protein and mRNA in the colon and spinal cord were detected by immunohistochemistry and quantitative real-time-PCR, respectively. Results: The IBS model rats had significantly higher AWR scores than the normal group ( P<0.01). After mild moxibustion treatment, the AWR score was significantly reduced (20 mm Hg, P<0.05; 40 mm Hg, 60 mm Hg and 80 mm Hg, P<0.01). The model group showed significantly more colonic glial cell line-derived neurotrophic factor (GDNF/GFRα3 (GDNF family receptor α3) protein and mRNA expression in the colon and spinal cord than the normal group ( P<0.01). Compared with the model group, the expression of GDNF/GFRα3 protein and mRNA in the colon and spinal cord of the rats were significantly decreased in the mild moxibustion group (colon: GDNF and GFRα3 protein, P<0.01; GDNF and GFRα3 mRNA, P<0.01; spinal cord: GDNF and GFRα3 protein, P<0.01; GDNF mRNA, P<0.05, GFRα3 mRNA, P<0.01). Conclusions: Our data suggest that moxibustion therapy may mitigate CRD-induced increases in the expression of GDNF and its receptor GFRα3 in the colon and spinal cord in a rat model of IBS.

scholarly journals Effect of Warm Acupuncture on “Dinghui Acupoint” and “Heart Acupoint” in Traditional Mongolian Medicine on Behaviors and Hypothalamic Inammatory Cytokines in Rats with Chronic Fatigue Syndrome

2019 ◽  
Vol 2 (2) ◽  
pp. 8
Author(s):  
Shumei Bai ◽  
Ling Shui ◽  
Qin Si ◽  
Yingsong Chen
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Chronic Fatigue ◽  
Normal Group ◽  
Acupuncture Group ◽  
Control Group ◽  
Model Group ◽  
Moxibustion Group ◽  
Fatigue Syndrome ◽  
Significant Difference ◽  
Traditional Mongolian Medicine

Objective: To observe the effects of warm acupuncture on “Dinghui Acupoint” and “Heart Acupoint” in Traditional Mongolian Medicine on behavior and hypothalamic inflammatory cytokines IL-1β, IL-6 and IFN-r in Rats with Chronic Fatigue Syndrome. Methods: SD rats were randomly divided into normal group, model group, warm acupuncture group and moxibustion positive control group. The latter three groups of rats were used to establish a model of rats with chronic fatigue syndrome (CFS) using a combination of physical fatigue and mental fatigue. When establishing the model of warm acupuncture group, “Dinghui Acupoint” and “Heart Acupoint” intervention was carried out; when establishing the model of moxibustion positive control group, “Zusanli Acupoint” intervention was carried out on both sides. Behavioral observations (body weight, exhaustive swimming time, tail suspension experiment, water maze) were performed before and after modeling. The hypothalamic inflammatory cytokines IL-1β, IL-6 and IFN-r were detected by ELISA method after warm acupuncture and moxibustion intervention. Results: After 21 days of modeling, the body weight of the rats in each group was significantly lower than that in the normal group, and there was a significant difference (P<0.01); Compared with the model group, the weight of the rats in the warm acupuncture group increased significantly, and there was a significant difference (P<0.01); Compared with the model group, the exhaustive swimming time of the rats in the warm acupuncture group was significantly prolonged, and there was a significant difference (P<0.01); Compared with the moxibustion group, the exhaustion time of the rats in the warm acupuncture group was relatively prolonged, and there was a significant difference (P<0.05); Compared with the normal group, the tail suspension time of the model group was significantly prolonged, and there was a significant difference (P<0.05); Compared with the model group, there was a significant difference in the duration of the suspension of the warm acupuncture group and the moxibustion group (P<0.01); Compared with the normal group, the total distance of the water maze test was shorter in the model group, and there was a significant difference (P<0.01); Compared with the model group, both the warm acupuncture group and the moxibustion group were prolonged, and there was a significant difference (P<0.05); Compared with the moxibustion group, the distance between the rats in the warm acupuncture group was relatively longer, but there was no significant difference (P>0.05); Compared with the normal group, IL-1β, IL-6 and IFN-r increased significantly in the model group and there was a significant difference (P<0.05); Compared with the model group, IL-1β and IL-6 in the warm acupuncture group was significantly decreased (P<0.05), and the IL-6 in the moxibustion group was significantly different (P<0.05); Compared with the model group, there was no significant difference between the IFN-r group and the moxibustion group (P>0.05); Compared with the moxibustion group, the levels of IL-1β, IL-6 and IFN-r were not significantly different (P>0.05). Conclusion: Warm acupuncture on “Dinghui Acupoint” and “Heart Acupoint” in Traditional Mongolian Medicine has the ability to improve the body’s defense and self-healing ability, improve chronic fatigue syndrome (CFS), and thus play a preventive role. The results of this research indicate that the warm acupuncture group and the moxibustion group have the same effect.

scholarly journals Understanding the Role of Gui-Zhi-Fu-Ling-Capsules (Chinese Medicine) for Treatment of Endometriosis in the Rat Model: Using NMR Based Metabolomics

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jue Zhou ◽  
Zhi-Ming Ding ◽  
Paul J. Hardiman
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Serum Levels ◽  
Normal Group ◽  
Sham Operation ◽  
Group Model ◽  
Model Group ◽  
Expression Levels ◽  
Glut 4 ◽  
Mrna Expression Levels

The objective of this study is to identify the changes of metabolites in the rat endometriosis models treated with Gui-Zhi-Fu-Ling-capsules (GZFLC), a classic Chinese medicinal formula, and to explore the effects of GZFLC on the serum levels of transforming growth factor-β1 (TGF-β1) and the mRNA expression levels of vascular endothelial growth factor (VEGF) and glucose transporter 4 (GLUT-4) in the endometriotic tissues. Forty female Wistar rats were randomly divided into the sham-operation group (Normal group), Model group, Danazol group, and GZFLC group. The serum levels of TGF-β1 were measured using enzyme-linked immune-sorbent assay (ELISA). The mRNA expression levels of VEGF and GLUT-4 in the endometriotic tissue of the rat endometriosis models were measured using real-time quantitative PCR. The metabolites in urine were detected by 1H NMR method. Eight identified metabolites of the NMR resonance were involved in the glycolysis metabolism. Among the 8 metabolites, Lactate, Acetate, TMA, and Formate were downregulated with GZFLC. Citrate, TMAO, Taurine, and Hippurate were unregulated with GZFLC. The serum levels of TGF-β1 in the Danazol and GZFLC groups were significantly higher than those of Normal group and significantly lower than the Model group. GZFLC treatment significantly decreased the GLUT-4 and VEGF mRNA expression levels in the endometriotic tissues of the endometriosis rats (P < 0.05). GZFLC significantly decreased the GLUT-4 mRNA expression levels in rats of GZFLC group compared with Danazol group. It is through regulating the metabolites changes of glycolysis or gluconeogenesis that GZFLC significantly affected the expression levels of TGF-β1, GLUT-4, and VEGF of the model rats with endometriosis.

scholarly journals Effects and Mechanism of Oxymatrine Combined with Compound Yinchen Granules on the Apoptosis of Hepatocytes through the Akt/FoxO3a/Bim Pathway

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Xian Zhang ◽  
Jiajia Ge ◽  
Xuejuan Zhu ◽  
Haifeng Zhang ◽  
Yuanzi Wang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Western Blot ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Rat Liver ◽  
Caspase 3 ◽  
Normal Group ◽  
Model Group ◽  
Apoptosis Rate ◽  
Liver Tissues

The aim of the present study was to investigate the effects and mechanism of oxymatrine (OMT) combined with compound yinchen granules (CYG) on the apoptosis of hepatocytes through the Akt/FoxO3a/Bim pathway in rats with acute liver failure. The rat model of acute liver failure was established using lipopolysaccharide/D-galactosamine (LPS/D-GalN). The expression of proteins in rat liver tissues was detected by western blot analysis. The mRNA expression of FoxO3a, Bim, Bax, Bcl-2, and caspase-3 in rat liver tissues was detected by RT-qPCR. The apoptosis rate of rat hepatocytes was determined by flow cytometry. Western blots showed that when compared with the normal group, the expression of p-Akt and p-FoxO3a in the model group was decreased ( P < 0.05 ), while the expression of Bim was increased ( P < 0.01 ). Compared with the model group, the expression of p-Akt and p-FoxO3a in the OMT group and the OMT combined with CYG groups was increased ( P < 0.05 or P < 0.01 ), while the expression of Bim was decreased ( P < 0.05 ). The Bax/Bcl-2 ratio and caspase-3 protein expression in the model group were significantly higher than those in the normal group ( P < 0.01 ). The Bax/Bcl-2 ratio and the expression of caspase-3 protein in the OMT group and the OMT combined with CYG groups were significantly lower than those in the model group ( P < 0.01 ). The results of RT-qPCR were consistent with those of western blot. The results of flow cytometry showed that the apoptosis rate of hepatocytes in the OMT group and the OMT combined with CYG groups was significantly lower than that in the model group ( P < 0.05 or P < 0.01 ). We concluded that LPS/D-GalN can induce apoptosis of hepatocytes in rats with acute liver failure through the Akt/FoxO3a/Bim pathway. OMT combined with CYG inhibits apoptosis of hepatocytes in rats with acute liver failure via the Akt/FoxO3a/Bim pathway.

scholarly journals Research on the Effects of the Extract of Polygala fallax Hemsl on Sex Hormones and ?-EP in Perimenopausal Rat Models

2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Siyuan Yang ◽  
Zhiyong Cao ◽  
Jiabao Chen ◽  
Gang Fang
Keyword(s):  
Menstrual Cycle ◽  
Sex Hormones ◽  
Dose Group ◽  
Low Dose ◽  
Normal Group ◽  
Dose Effect ◽  
High Dose Group ◽  
High Dose ◽  
Model Group ◽  
Rat Models

Objective: To study the effects of the ethnic medicine Polygala fallax Hemsl with Guangxi characteristics on the sex hormones and ?-EP in research objective perimenopausal rat models. Methods: 40 female SPF rats were randomly divided into 4 groups, including the normal, model, high-dose and low-dose groups. Rats of three groups except for the normal one were treated with perimenopausal modelling through the method of subcutaneous injection of compound 4-VCD for 15 consecutive days. Rats of the normal and model group were normally fed without any treatment. Rats of the high-dose and low-dose groups were administered by high- and low-dose intragastric administration of the extract of Polygala fallax Hemsl. According to the menstrual cycle of the vaginal smear of the rat, each menstrual cycle is a course of treatment and 6 consecutive courses of treatment would be given. The indexes of serum sex hormones (E2, FSH, LH) and ?-EP of rats in each group were observed after treatment. Results: After the treatment of 6 cycles, for the levels of ?-EP and E2, the model group was lowest (P<0.05), the normal group was highest (P<0.05); and the high-dose group was higher than the low-dose group; For the levels of FSH and LH, the normal group was lowest (P<0.05), the model group was highest (P<0.05), and the high-dose group was lower than the low-dose group. Conclusion: Guangxi characteristic national medicine Polygala fallax Hemsl can effectively improve the levels of serum sex hormones and ?-EP in perimenopausal rat models and relieve the related symptoms with a certain dose-effect relationship.

scholarly journals Treatment with an SSRI antidepressant restores hippocampo-hypothalamic corticosteroid feedback and reverses insulin resistance in low-birth-weight rats

2010 ◽  
Vol 298 (5) ◽  
pp. E920-E929 ◽  
Author(s):  
Esben S. Buhl ◽  
Thomas Korgaard Jensen ◽  
Niels Jessen ◽  
Betina Elfving ◽  
Christian S. Buhl ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Birth Weight ◽  
Insulin Sensitivity ◽  
Low Birth Weight ◽  
Mrna Expression ◽  
Hpa Axis ◽  
Whole Body ◽  
Oral Glucose ◽  
Red Muscle ◽  
Hpa Axis Activity

Low birth weight (LBW) is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4–5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phospho enolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser473phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW ( P < 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion ( P < 0.05 vs. Cx), whole body insulin resistance ( P < 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression ( P < 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser473phosphorylation. The ESC treatment normalized corticosterone secretion ( P < 0.05 vs. LBW), whole body insulin sensitivity ( P < 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression ( P < 0.05), and red muscle PKB Ser473phosphorylation ( P < 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats.

Markers of HPA-axis activity and nucleic acid damage from oxidation after electroconvulsive stimulations in rats

2019 ◽  
Vol 31 (6) ◽  
pp. 287-293
Author(s):  
Anders Jorgensen ◽  
Katrine Breitenstein ◽  
Otto Kalliokoski ◽  
Allan Weimann ◽  
Trine Henriksen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Hpa Axis ◽  
Severe Depression ◽  
Male Rats ◽  
Therapeutic Effects ◽  
Middle Aged ◽  
Dna And Rna ◽  
Rna Damage ◽  
Hpa Axis Activity

AbstractObjective:Oxidative stress has been suggested to increase after electroconvulsive therapy (ECT), a treatment which continues to be the most effective for severe depression. Oxidative stress could potentially be mechanistically involved in both the therapeutic effects and side effects of ECT.Methods:We measured sensitive markers of systemic and central nervous system (CNS) oxidative stress on DNA and RNA (urinary 8-oxodG/8-oxoGuo, cerebrospinal fluid 8-oxoGuo, and brain oxoguanine glycosylase mRNA expression) in male rats subjected to electroconvulsive stimulations (ECS), an animal model of ECT. Due to the previous observations that link hypothalamic–pituitary–adrenal (HPA)-axis activity and age to DNA/RNA damage from oxidation, groups of young and middle-aged male animals were included, and markers of HPA-axis activity were measured.Results:ECS induced weight loss, increased corticosterone (only in middle-aged animals), and decreased cerebral glucocorticoid receptor mRNA expression, while largely leaving the markers of systemic and CNS DNA/RNA damage from oxidation unaltered.Conclusion:These results suggest that ECS is not associated with any lasting effects on oxidative stress on nucleic acids neither in young nor middle-aged rats.

scholarly journals Effects of dexmedetomidine on the RhoA /ROCK/ Nox4 signaling pathway in renal fibrosis of diabetic rats

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 890-898 ◽  
Author(s):  
Chen Jihua ◽  
Chen Cai ◽  
Bao Xubin ◽  
Yu Yue
Keyword(s):  
Renal Function ◽  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Rat Kidney ◽  
Diabetic Rats ◽  
Immunohistochemical Method ◽  
Model Group ◽  
Protein Expressions ◽  
Masson Staining

AbstractObjectiveTo investigate the effects and mechanisms of dexmedetomidine (Dex) on model rats of diabetic nephropathy (DN).MethodsRats were divided into NC, model, Dex-L (1μg/ kg), Dex-M (5μg/kg) and Dex-H (10μg/kg) groups. Rats in all groups except in the NC group were injected with streptozotocin (STZ) combined with right nephrectomy. Rats in Dex (1, 5 and 10μg/kg) groups received gavage with Dex (1, 5 and 10μg/kg). After 4 weeks, rats were sacrificed and kidneys were collected. HE staining was performed for a renal injury. Masson staining was applied to detect the fibrotic accumulation in rat kidney. Radioimmunoassay was used to test the renal function. Immunohistochemical method was used to detect protein expressions of RhoA, p-MYPT and Nox4 in rat kidney.ResultsCompared with the NC group, the levels of urine microalbumin in protein, α1-MG and β2-MG, renal fibrotic accumulation, RhoA, p-MYPT, Nox4 and α-SMA in model group increased significantly (P＜0.001, respectively). Compared with the model group, Dex low, medium and high groups improved the deposition of renal fiber in rats, inhibited the expression levels of microalbumin, α1-MG and β2-MG in urine and decreased expression of RhoA, p-MYPT, Nox4 and α-SMA proteins (P＜0.05, P＜0.01).ConclusionDex is possible to inhibit the expression of α-SMA and renal fibrous substance deposition in rat kidney via RhoA/ROCK/Nox4 signaling pathway, thereby reducing early kidney damage in model rats.

scholarly journals Effects of paeonol on the expression of NF-κB pathways in human umbilical veins endothelial cells induced by homocysteine

2015 ◽  
Vol 10 (3) ◽  
pp. 604
Author(s):  
Qian Xu ◽  
Kai Cao ◽  
Yan-Hong Xiao ◽  
Chao Du ◽  
Xian-Hui Dong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Protein Expression ◽  
Cell Viability ◽  
Protein Degradation ◽  
Mrna Expression ◽  
Umbilical Vein ◽  
Model Group ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

<p class="Abstract">The aim of this study was to investigate the effects of paeonol on the expression of NF-κB pathway induced by homocysteine. After Human umbilical vein endothelial cells exposed to homocysteine for 24 hours,  paeonol (0.15-0.6 mmol/L) improved the cell viability (p&lt;0.05). NF-κB p65 mRNA expression was reduced largely (p&lt;0.05) and IκB-α protein expression increased significantly (p&lt;0.01). The staining of NF-κB p65 in nucleus was not as much as those in homocysteine injured model group (p&lt;0.01). Therefore, paeonol can inhibit IκB-α protein degradation and suppress NF-κB transferred into nuclear in order to inhibit the activation of NF-κB.</p><p> </p>

Maternal undernutrition during the first week after conception results in decreased expression of glucocorticoid receptor mRNA in the absence of GR exon 17 hypermethylation in the fetal pituitary in late gestation

2013 ◽  
Vol 4 (5) ◽  
pp. 391-401 ◽  
Author(s):  
S. Zhang ◽  
O. Williams-Wyss ◽  
S. M. MacLaughlin ◽  
S. K. Walker ◽  
D. O. Kleemann ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Mrna Expression ◽  
Hpa Axis ◽  
Early Embryo ◽  
Late Gestation ◽  
Control Group ◽  
Fetal Sheep ◽  
Maternal Undernutrition ◽  
Stress Responsiveness ◽  
Periconceptional Period

Exposure to maternal undernutrition during the periconceptional period results in an earlier prepartum activation of the fetal hypothalamo–pituitary–adrenal (HPA) axis and altered stress responsiveness in the offspring. It is not known whether such changes are a consequence of exposure of the oocyte and/or the early embryo to maternal undernutrition in the periconceptional period. We have compared the effects of ‘periconceptional’ undernutrition (PCUN: maternal undernutrition imposed from at least 45 days before until 6 days after conception), and ‘early preimplantation’ undernutrition (PIUN: maternal undernutrition imposed for only 6 days after conception) on the expression of genes in the fetal anterior pituitary that regulate adrenal growth and steroidogenesis, proopiomelanorcortin (POMC), prohormone convertase 1 (PC1), 11β-hydroxysteroid dehydrogenase type 1 and 2 (11βHSD1 and 2) and the glucocorticoid receptor (GR) in fetal sheep at 136–138 days of gestation. Pituitary GR mRNA expression was significantly lower in the PCUN and PIUN groups in both singletons and twins compared with controls, although this suppression of GR expression was not associated with hypermethylation of the exon 17 region of the GR gene. In twin fetuses, the pituitary 11βHSD1 mRNA expression was significantly higher in the PIUN group compared with the PCUN but not the control group. Thus, exposure of the single or twin embryo to maternal undernutrition for only 1 week after conception is sufficient to cause a suppression of the pituitary GR expression in late gestation. These changes may contribute to the increased stress responsiveness of the HPA axis in the offspring after exposure to poor nutrition during the periconceptional period.

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