中风病痰湿证与垂体-肾上腺激素水平关系的探讨

目的 :探讨中风病痰湿证与垂体 -肾上腺激素水平关系 ,以从微观角度寻找中风症证候的辨证依据。方法 :应用“证候辨证量化”诊断的方法对151例经CT或MRI确诊为缺血性中风始发态的患者进行量化评分 ,将其分为痰湿证和非痰湿证两组 ,同时用放射免疫分析(RIA)法测定本病患者及健康体检者的促肾上腺皮质激素(ACTH)、皮质醇(CS)含量并进行对照。结果 :两组患者ACTH、CS含量均升高 ,与健康对照组比较具有非常显著的差异(P<0.001)。而痰湿证组ACTH、CS含量较非痰湿证组高 ,两组比较有统计学意义(P<0.05)。结论 :缺血性中风痰湿证与ACTH、CS有密切关系 。

Possible involvement of integrin signaling pathway in the process of recovery from restraint stress in rats

Objective To search novel genes or pathways involved in the recovery process after restraint stress in rats. Methods We compared the hypothalamus transcriptional profiles of two different recovery patterns （fast recovery vs slow recovery） from restraint stress in rats using oligonucleotide microarray, the recovery pattern was determined by the decrement of plasma adrenocorticotropic-hormone （ACTH） and corticosterone levels during one hour recovery period after stress. A real-time quantitative RT-PCR was applied to validate the differential expressed genes. Results Analysis of the microarray data showed that most of genes were not differentially expressed between fast recovery group and slow recovery group. Among the differentially expressed genes we found that talin, together with serine/threonine protein phosphatase PPl-beta catalytic subunit （PP-1B） and integrin α-6 precursor （VLA-6） genes, were at least 1.5 fold upregulated in the fast recovery group, while junctional adhesion molecule 1 （F11r） was 1.5 fold down-regulated in the fast recovery group. Conclusion The results implied that integrin signaling pathway may be involved in the recovery from restraint stress in rats. The present study provided a global overview of hypothalamus transcriptional profiles during the process of recovery from the restraint stress in rats. The integrin signaling pathway seems to be involved in the recovery process, which deserves further study to clarify the integrin-mediated recovery mechanism after restraint stress.

Changes of serum adrenocorticotropic hormone and cortisol levels during sleep seizures

Objective Measuring the serum concentrations of adrenocorticotropic hormone （ACTH） and cortisol in epileptic seizures during sleep to investigate their link to the EEG changes. Methods Pre-surgical evaluation was performed by videoEEG monitoring using 24 channel recording. Thirty six epilepsy patients could be attributed to two groups： 28 patients had spontaneous seizures, and the other 8 patients whose seizures were induced by bemegride. Another 11 persons with confirmed psychogenic non-epileptic seizures （PNES） served as control group. Blood samples were obtained at five points： wake （08：00 a.m.）, sleep （00：00 a.m.）, and shortly before, during and after an epileptic seizure. The serum ACTH and cortisol were measured and analyzed by chemiluminescent immunoassay. Results The levels of ACTH and cortisol in serum underwent significant changes： declining below the average sleep-level shortly before seizures, increasing during seizures, and far above the average wake-level after seizures （P 〈 0.001）. Such changes did not occur in the control group （P 〉 0.05）. The ACTH and cortisol levels had no significant difference between spontaneous group and bemegride-induced group （P 〉 0.05）. Conclusion The serum concentrations of ACTH and cortisol during sleep seizures are linked with pre-ictal and ictal EEG changes in epilepsy patients.

Effect of electro-acupuncture on substance P, its receptor and corticotropin-releasing hormone in rats with irritable bowel syndrome

AIM： To investigate the effect and mechanism of electro-acupuncture lEA） at ST25 and ST37 on irritable bowel syndrome （IBS） of rats. METHODS： A total of 21 male Sprague-Dawley rats were randomly divided into normal group, model group and EA group. A rat model of IBS was established by constraining the limbs and distending the colorectum of rats. Rats in EA group received bilateral EA at ST25 and ST37 with a sparse and intense waveform at a frequency of 2/50 Hz for 15 min, once a day for 7 d as a course. Rats in normal and model groups were stimulated by distending colorectum （CR）. An abdominal withdrawal reflex （AWR） scoring system was used to evaluate improvements in visceral hypersensitivity. Toluidine blue-improved method, immunohistochemistry and radioimmunoassay were used to observe mucosal mast cells （MC）, changes of substance P （SP） and substance P receptor （SPR） in colon and change of corticotropin-releasing hormone （CRH） in hypothalamus. RESULTS： The threshold of visceral sense was significantly lower in model group than in normal group,and significantly higher in EA group than in model group. The number of mucosal MC was greater in model group than in normal group and significantly smaller in EA group than in model group. The CRH level in hypothalamus of rats was significantly higher in model group than in normal group, which was remarkably decreased after electro-acupuncture treatment. The SP and SPR expression in colon of rats in model group was decreased after electro-acupuncture treatment. CONCLUSION： EA at ST25 and ST37 can decrease the number of mucosal MC and down-regulate the expression of CRH in hypothalamus, and the expression of SP and SPR in colon of rats with IBS.

Peripheral corticotropin releasing hormone mediates post-inflammatory visceral hypersensitivity in rats

AIM:To investigate whether peripheral corticotropin releasing hormone (CRH), which is up-regulated in intestinal inflammation, mediates the post-inflammatory visceral hypersensitivity in a rat model of colitis. METHODS:We measured mucosal myeloperoxidase (MPO) activity as a marker of inflammation, plasma CRH level, and abdominal withdrawal reflex (AWR) to colorectal distension as a visceral nociceptive response at 2, 7 and 14 d after the induction of colitis with 4% acetic acid. RESULTS:Colonic inflammation, quantified by MPO activity, significantly increased on d 2 and subsided thereafter, which indicated a resolution of inflammation within 7 d. On the contrary, plasma CRH level and AWR score were increased on d 2, remained high on d 7, and returned to control level on d 14. Intraperitoneal injection of a CRH antagonist, astressin (30 μg/kg), significantly attenuated the post-inflammatory visceral hypersensitivity on d 7. Furthermore, intraperitoneal administration of CRH (3 and 10 μg/kg) mimicked the post-inflammatory visceral hypersensitivity in naive rats. CONCLUSION:These results suggest that increased peripheral CRH mediates the enhanced visceral nociception in rats recovered from experimental colitis.

Suspended moxibustion relieves chronic visceral hyperalgesia and decreases hypothalamic corticotropin-releasing hormone levels

AIM:To evaluate the effect of suspended moxibustion(SM) on rectal sensory thresholds and to analyze the possible mechanisms involved in SM treatment of chronic visceral hypersensitivity(CVH) in rats.METHODS:SM was administered once daily to 37-dold CVH rats for 7 d.The two pairs of acupoints(ST25 and ST37,bilateral) were simultaneously treated with SM.Each treatment lasted for 30 min.Rats undergoing treatment with SM were not anesthetized.Untreated CVH rats and normal rats were used as controls.The abdominal withdrawal reflex was determined 30-90 min after the seven treatments.The hypothalamic corticotropin-releasing hormone(CRH) mRNA level was measured using real-time quantitative reverse transcriptionpolymerase chain reaction.RESULTS:We found that SM treatment significantly decreased visceral sensitivity to colorectal distention in this rat model.In treated animals,SM also decreased the relative hypothalamic CRH mRNA expression level to control levels.CONCLUSION:Lower hypothalamic CRH levels may mediate the beneficial effects of SM in this rat irritable bowel syndrome model.

MAGNETIC RESONANCE IMAGING CHARACTERISTICS AND SURGICAL RESULTS OF ADRENOCORTICOTROPIN-SECRETING PITUITARY ADENOMAS

Objective To evaluate magnetic resonance imaging （MRI） characteristics and surgical results of adrenocorticotropin （ACTH） -secreting pituitary adenomas. Methods MRI characteristics and relationship between MRI positive rate and surgical results of 266 patients with pathologically confn＇med Cushing＇s disease were analyzed retrospectively. All patients underwent thin-section sagittal and coronal scans of the pituitary gland before and after administration of gadolinium-diethylene triamine pentaacetic acid （Gd-DTPA） on a 1. 5 Tesla MR/scanner, and dynamic enhanced MR/was performed in 39 patients. All patients underwent transsphenoidal adenomectomy. Endocrinological examinations and assessments were performed. Results Preoperative MR/revealed normal results in 41 （ 15.4% ） cases, microadenoma in 179 （67. 3% ）, macroadenoma in 42 （ 15.8% ）, and huge adenoma in 4 （ 1.5% ）. Pituitary apoplexy was found in 13 （4.9%） cases. Positive rate of ACTH-secreting adenomas was 84.6% （225/266） on MR/scans, and that of small microadenomas was 87.2% （34/39） on dynamic enhanced MRI scans. Preoperative endocrinological tests of 199 cases supported the diagnosis of typical Cushing＇s disease, while the other 67 cases had atypical endocrinological results. The endocrinological cure rate, remission rate, and inefficacy rate were 85.7%, 7.9%, and 6. 4%, respectively. There was no difference in the initial endocrinological cure rate between the patients with positive and normal MRI results （90% vs. 87. 8%, P =0. 904）. Conclusions Enhanced coronal pituitary MR/ is helpful for preoperative localization of ACTH-secreting pituitary microadenoma. Dynamic enhanced MR/may improve detection rate of microadenoma. There is no marked difference in the surgical results for patients with preoperative MR/results indicating presence or absence of microadenoma.

Effects of repetitive transcranial magnetic stimulation on hypothalamic-pituitary-adrenal axis of patients with depression

Objective： To investigate the effects of sleep electroencephalogram-modulated repetitive transcranial magnetic stimulation （SEM-rTMS） and conventional rTMS （C-rTMS） on the activity of hypothalamic-pituitary-adrenal （HPA） axis in patients with depression. Methods： In a double-blind, randomized controlled trial, 164 patients diagnosed with depression were randomized to treatment with SEM-rTMS （n=57）, C-rTMS （n=55） or sham rTMS （n=52） for 30 rain every day for 10 d. Before and after treatment plasma concentrations of adrenocorticotropic hormone （ACTH） and cortisol （CORT） were measured, and the 24-item Hamilton Depression Rating Scale （HAMD-24） was used for assessment. Results： The HAMD-24 scores and plasma ACTH and CORT concentrations of these depressive patients before treatment were significantly different from those of the normal control group （P〈0.05）. The HAMD-24 scores and plasma ACTH and CORT concentrations in the SEM-rTMS group and conventional rTMS group were decreased significantly （P〈0.05）. There was a significant positive correlation between the HAMD-24 scores and plasma ACTH （n=240, r=0.105, P=0.048） and CORT concentrations （n-240, r=0.126, P=0.023） in the patients with depression before and after treatment. Conclusion： The antidepressant effect of rTMS, including SEM-rTMS, may be related to its decreasing HPA axis activity. （This trail was registered. No： ChiCTR-TRC-00000465）

Corticotropin-releasing factor secretion from dendritic cells stimulated by commensal bacteria

AIM:To study the production and secretion of corticotropin-releasing factor (CRF) by dendritic cells and the influence of commensal bacteria.METHODS:JAWSⅡ cells (ATCC CRL-11904),a mouse dendritic cell line,were seeded into 24-well culture plates and grown for 3 d.Commensal bacterial strains of Clostridium clostrodiiforme (JCM1291),Bacteroides vulgatus (B.vulgatus) (JCM5856),Escherichia coli (JCM1649),or Fusobacterium varium (F.varium) (ATCC8501) were added to the cells except for the control well,and incubated for 2 h.After incubation,we performed enzyme-linked immunosorbent assay for the cultured medium and reverse transcription polymerase chain reaction for the dendritic cells,and compared these values with controls.RESULTS:The level of CRF secretion by control dendritic cells was 40.4±6.2 pg/mL.The CRF levels for cells incubated with F.varium and B.vulgatus were significantly higher than that of the control (P<0.0001).CRF mRNA was present in the control sample without bacteria,and CRF mRNA levels in all samples treated with bacteria were above that of the control sample.F.varium caused the greatest increase in CRF mRNA expression.CONCLUSION:Our results suggest that dendritic cells produce CRF,a process augmented by commensal bacteria.

Arctic spring: the arrival biology of migrant birds

On arrival in the Arctic, migrant birds must adjust their physiology and behavior to unpredictable snow cover, weather, food sources and predator pressure. In other words they must be resistant to environmental perturbations (stress) so that they can migrate to their tundra nesting areas and settle on territories as soon as possible. They can then begin breeding as soon as when environmental conditions become favorable. They do this partly by using micro-habitats such as areas where snow depth is low, and patches of tundra that melt out rapidly (especially near willows Salix sp). Ground temperatures increase dramatically within hours after exposure to sun; and invertebrate activity begins simultaneously. Wind speeds are attenuated almost completely within 10 cm of the ground in willows and tussock tundra. The combination of these conditions provides an ideal refuge, especially for passerine migrants in early spring. However, if conditions worsen, the birds can leave. There are adjustments of the adrenocortical responses to stress because arctic conditions in spring are potentially severe, at least compared with wintering grounds to the south. Secretion of corticosterone in response to acute stress is enhanced at arrival in males, accompanied by a decrease in sensitivity to negative feedback and a change in responsiveness of the adrenal cortex cells to adrenocorticotropin. There is also an increase in levels of corticosterone-binding globulin (CBG) so that the actions of corticosterone are buffered according to the severity of environmental conditions. Regulation at the level of genomic receptors, particularly the low affinity glucocorticosteroid-like receptor for corticosterone in brain and liver, may be important; and non-genomic actions of corticosterone may play a major role too. In other words, the hormone-behavior system associated with arrival biology is highly flexible.

Effects of high dose glucocorticoid on expression and mRNA transcription of corticotropin releasing hormone in hypothalamus paraventricular nucleus of rats

Objective： To explore the effect of high dose of glucocorticoid （GC） on the synthesis of corticotropin releasing hormone （CRH） and transcription of its mRNA in hypothalamus paraventricular nuclei （PVN） in order to investigate its difference with that of traditional GC effects and to add a new possible explanation to the mechanism of clinical applications of high dose of GC. Methods： A total of 60 rats were divided into 5 groups： blank control, 10^-6 mol/L dexamethasone （DEX） group, 10^-9 mol/L DEX group, 0.9% saline group and GR blocking group （10^-2mol/L RU486）. All agents were administrated through the femoral vein. CRH protein expression was measured by immunohistochemistry and laser confocal scanning microscopy （LCSM）; CRH mRNA level was explored by in situ hybridization. Results： 10^-6 mol/L DEX made CRH mRNA transcripted after 20 min and its protein expressed in PVN after 30 min, while normal level of DEX and 0.9% saline could not. If GR was blocked in advance, the effect of high dose of DEX disappeared. Conclusion ： High dose of GC can have CRH increased in PVN, which differs to the effect of traditional GC. And mGRH may play an important role in the effect of high dose of GC but not classic iGR.

Estrogen inhibits corticotropin-releasing hormone production in primary human placental cells

Objective: To study the inhibition effects of estrogen on the production of corticotropin-releasing hormone in human placental cells. Methods: Primary cultured placental cells were treated by ICI182, 780, a complete ER antagonist , and Tamoxifen, an ERa-mixed agonist/antagonist and ERβ antagonist for 24 h. The supernatant was havested for the radioimmunoassay of CRH. Results: 17β-estradiol inhibited the secretion of corticotropin-releasing hormone in human placental (P<0.05). ICI182, 780 stimulated the secretion of corticotropin-releasing hormone in human placental (P<0.05). Conclusion: Estrogen represses the synthesis and secretion of corticotropin-releasing hormone in human placental, which is possibly mediated by ERa.

A Small Solitary Pulmonary Nodule Discovered by ^(18)F-fluorodeoxyglucose Positron Emission Tomography and CT: Rare Infection Instead of Rare Tumor

THE causes of Cushing＇s syndrome are mainly di- vided into adrenocorticotropic hormone （ACTH） dependent and independent. ACTH dependent hypercortisolism represents excess ACTH se-creting by the pituitary or tumor outside the pituitary; and the latter one is also called as ectopic ACTH syndrome. Thorax is the most common location of causative lesions for ectopic ACTH syndrome, and the size of lesion is too small to be detected in some cases.1＇ 2 Cryptococcal pneumonia usually occurs in immunocompromised patients and excess cortisol production can theoretically produce a state of immunodeficiency. Development of cryptococcal pneumonia concomitant with Cushing syndrome （CS） was rare. Here, we report a case of pulmonary nodule in a patient with CS differentiated with ectopic ACTH-producing tumor. Crypto- coccal pneumonia was diagnosed followinglung resection.

Effect of Xylazine-Ketamine Anesthesia on Blood ACTH, Cortisol, Adrenaline, Insulin and Glucose in Ovariohysterectomized Cats

A study has been carried out with fourteen healthy mature cats in order to determine the effect of a xylazine-ketamine anesthetic protocol （group X/K） on blood concentrations of adrenaline, ACTH （adrenocorticotropic hormone）, cortisol, insulin and glucose in comparison with a control group （group K--no anesthesia and surgery）. The animals were randomly allocated in two groups （n = 7）. The premeditation in the experimental group was made with xylazine 2 mg/kg intramuscularly. Induction and maintenance of anesthesia were made with ketamine 10 mg/kg intramuscularly. Ovariohysterectomy was performed upon occurrence of deep anesthesia. Blood specimens were obtained at 0, 30, 60, 120 min and 24 h from the two groups. Pronounced decrease in blood ACTH, cortisol, and adrenaline in group X/K was determined by the 30 min. Significant hyperglycemia together with hyperinsulinemia in the X/K group was established at the 120 min from the beginning of the anesthesia. Anesthesia with xylazine and ketamine led to reduction of the blood levels of stress hormones immediately after the beginning of anesthesia and caused a remarkable hyperglycemia with hyperinsulinemia.

EAE （Experimental Autoimmune Encephalomyelitis）, Corticotropin-Releasing Factor and the Blood Brain Barrier

EAE （experimental autoimmune encephalomyelitis） is an established, inducible animal model employed in the study of MS （multiple sclerosis） characterized by inflammation, BBB （blood brain barrier） malfunction, demyelination and neuronal disruption. CRF （corticotropin releasing factor） is a neuropeptide critically associated with immune function, BBB permeability, and the hypothalamic-pituitary-adrenal axis. Potential CRF targets in the brain include astrocytes, as well as endothelial cells of cerebral microvessels, since they have been reported to express CRFR （CRF receptors）. Further, both of these cell types function critically in regulating BBB permeability. CRF-BP （CRF binding protein） is also expressed in both neurons and glial cells. Changes in the cortical CRF system could be a contributing factor to the BBB disruption associated with MS/EAE and has been suggested to play a protective role against cytokine-induced inflammation. The current study assessed alterations associated with the C57BL/6 mouse model of EAE in the cortical CRF system and correlated these events with changes to the microvascular unit. Immunohistochemical confocal microscopy was used to analyze the distribution of CRF, CRF-BP, and CRFR in the mouse cerebral cortex. The authors observed a reduction in detectable CRF immunofluorescence in the EAE motor cortex, an increase in CRFBP immunoreactivity in EAE astrocytes and a concurrent reduction in astrocytic CRFR immunofluorescence. Staining techniques were used to visualize astrocytes/microvessels to document alterations in BBB integrity. Changes in the CRF system were associated with a modification of the blood brain barrier as manifested by a poorly defined astrocytic barrier in EAE microvessels. Evidence suggests that manipulation of CRF signaling pathways offers an intriguing target for interventional therapies designed to modify BBB permeability that may be beneficial for treating disease states such as MS.

5例伴有抽搐的多种垂体激素缺乏症的诊治分析

伴有促肾上腺皮激素（corticotropin hormone，ACTH）缺乏的多种垂体激素缺乏症（multiple pituitary hormone deficiency，MPHD）患儿，因在感染、创伤、手术等应激状态下可出现肾上腺危象和低血糖抽搐，是严重的儿科急诊之一。由于发病率低，临床表现不典型，少数患者有反复抽搐，以发热、呕吐、腹痛或腹泻、脱水和低血糖、低血压、低血钠的急诊形式就诊，常得不到及时诊治。

Effect of electroacupuncture at conception vessel and governor vessel on correlative signals of stress-injury-repair in cerebral ischemia reperfusion rats

Objective To explore the effect of electroacupuncture at conception vessel and governor vessel on correlative signals of inflammatory response stressinjury-repair in cerebral ischemia reperfusion rats. Methods A total of 216 rats were included in the experiment, of which 192 rats were randomly divided into four groups, including sham operation group（group A）, model group（group B）, governor vessel group（group C）, and conception vessel and governor vessel group（group D）, 48 rats in each group. The rats in each group were further divided into six sub-groups, including 12 h group, 24 h group, 48 h group, 72 h group, 96 h group and 144 h group. MCAO operation course was simulated in group A, and the common carotid artery, internal carotid artery and external carotid artery on the right side were exposed, without insertion of suture or treatment. After completion of modeling in group B, treatment was not conducted. After completion of modeling in group C, ＂Shuǐgōu（水沟 GV 26）＂, ＂Bǎihuì（百会 GV 20）＂ and ＂Dàzhuī（大椎 GV 14）＂ of governor vessel were selected, and electroacupuncture device was connected with ＂GV 14＂ and ＂GV 20＂. After completion of modeling in group D, ＂GV 26＂, ＂GV 20＂ and ＂GV 14＂ of governor vessel, and ＂Qìhǎi（气海 CV 6）＂, ＂Guānyuán（关元 CV 4）＂ and ＂Chéngjiāng（承浆 CV 24）＂ of conception vessel were selected; electroacupuncture device was connected with ＂GV 14＂ and ＂GV 20＂, ＂CV 4＂ and ＂CV 6＂. Neurological severity score was conducted.Enzyme linked immunosorbent assay（ELISA） was applied to determine the concentration of peripheral serum adrenocorticotropic hormone（ACTH） of rats, and immunohistochemical method was adopted to detect the expression levels of tumor necrosis factor α（TNF-α） and transforming growth factor β1（TGF-β1） in brain tissue of rats. The other 24 rats were also randomly divided into four groups mentioned above, 6 rats in each group, to detect cerebral ischemie volume. Results Compared with group B, the ischemia volume in brain tissue at 144 h after cerebral ischemia reperfusion decreased significantly in group C and group D（P〈0.05）, and the ischemia volume in group D was less than that in group C（P〈0.05）. The neurological impairment scores of group C and group D at all time points were lower than those of group B, and the differences were statistically significant（all P〈0.05）. The scores of group D at all time points were lower than those of group C, and the differences since 24 h were statistically significant（all P〈0.05）. Compared with group B, the excessive expression of ACTH was suppressed dynamically and generally in group C and group D（P〈0.05）; the expression level of TNF-α was down-regulated and TGF-β1 was up-regulated as well in group C and group D（P〈0.05）. The effect in group D was superior to that in group C. Conclusion Electroacupuncture at conception vessel and governor vessel can protect brain through the intervention of the expression of correlative signals of inflammatory response stress-injury-repair of cerebral ischemia reperfusion.

Increased expression level of corticotropin-releasing hormone in the amygdala and in the hypothalamus in rats exposed to chronic unpredictable mild stress

Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to stressors.In the present study,the effect of chronic unpredictable mild stress（CUMS）on CRH neurons was investigated in rat brain.Methods The rats were exposed to one of the stressors each day for 21 d.Immunostaining was performed to detect the CRH-positive neurons in the paraventricular nucleus（PVN）of the hypothalamus and in amygdala.Results After the stress protocol,the animals showed a reduction in body weight gain as well as reduced sucrose preference and locomotor activity.Interestingly,the CRH neurons in both PVN and central nucleus of the amygdala（CeA）were stimulated by CUMS.The densities of CRH-containing neurons in both PVN and CeA were significantly higher than those in control group.Conclusion The CRH systems in PVN and CeA may both contribute to depression-like behaviors during CUMS.

The cAMP-mediated protein kinase signal transduction pathway is involved in the pyrogenic effect of CRH in rats

To determine whether the cyclic adenosine monophosphate (cAMP) mediated protein kinase signal transduction pathway is involved in the pyrogenic action of corticotropin releasing hormone (CRH) in rats.Methods Corticotropin releasing hormone, 2', 3 '-dideoxyadenosine (DDA) and adenosine-3', 5'(cyclic) monophosphorothionate, Rp-lsomer (Rp-cAMPS), were administered intracerebroventricularly (i.c.v.). The colonic temperature was measured using a thermistor, and the content of cAMP in the hypothalamus was determined by radioimmunoassay. Hypethalemic incubation was used to assess the effects of CRH on the content of cAMP in the hypothalamus in vitro.Results Microinjection (i.c.v.) of CRH (2.5 μg, 5.0 μg and 10 μg) caused increases in colonic temperature and the hypothalemus cAMP level in conscious rats. CRH increased hypothalemus cAMP level in vitro. The pyrogenic effects of CRH were abolished or markedly inhibited by prior injection (i. c. v. ) of an adenylate cyclase inhibitor, DDA (30 μg), or an inhibitor of cAMP-dependent protein kinase, Rp-cAMPS (15 μg).Conclusion cAMP mediates the pyrogenic action of centrally administered of CRH in rats, and protein kinase A may play an important role in the central CRH-induced fever. The cAMP-dependent protein kinase signal transduction pathway may be involved in the central mechanisms of the pyrogenic action of CRH in rats.

Characterization of urocortin in human pregnancy

Objective To examine whether urocortin is produced locally to regulate utero-placental vascular tone during pregnancy.Methods We examined the distribution of urocortin in human placenta, fetal membranes and uterine tissue at term in the presence and absence of labor using a urocortin antibody produced in our laboratory and the immunoperoxidase staining method. Subsequently, we tested urocortin secretion from chorio-decidual cells in vitro using an immunoblot technique. Then, we tested whether urocortin is present in maternal plasma throughout gestation using a radioimmunoassay. A Sephadex G-50 column was used to examine whether immunoreactive urocortin (IR-urocortin) in maternal plasma is the same as synthetic urocortin.Results IR-urocortin was observed in vascular smooth muscle of myometrium decidual stromal cells, syncytiotrophoblast and amnion epithelium. No differences in staining intensity for urocortin were detected between tissues obtained in the absence or presence of labor. Staining intensity for IR-urocortin was greatest in the decidua, suggesting this may be the main site of urocortin production. Positive staining for urocortin was observed in 40% of chorio-decidual cells with 34% of these cells secreting urocortin under basal conditions. Urocortin was detectable in maternal plasma from 16 weeks gestation and concentrations did not change as gestation progressed. IR-urocortin in the maternal plasma eluted from a Sephadex G-50 column at the same site as synthetic urocortin and had a calculated retention co-efficient of 0.44.Conclusion This study indicates that urocortin is produced by the decidua during human pregnancy and is detectable in maternal plasma. These data are consistent with the hypothesis that urocortin is produced locally by the decidua and may act to regulate utero-placental blood flow.