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991.
Ontogeny of prolactin releasing and inhibiting activities in the posterior pituitary of male rats 总被引:1,自引:0,他引:1
Plasma PRL levels in male rats are highest during the peripubertal period. We previously reported that the posterior pituitary (PP) contains a potent PRL-releasing factor (PRF), a trypsin-insensitive small peptide which is distinct from known PRL secretagogues. The objectives were to determine the ontogeny of PRF activity in the PP as well as age-related alterations in anterior pituitary responsiveness to PRF. We also explored if the PP contains a nondopaminergic PRL-inhibiting factor (PIF). PRF/PIF activities were assessed by the ability of PP extracts to alter PRL release from cultured anterior pituitary cells. The PP were extracted with perchloric acid and lyophilized, thus eliminating endogenous dopamine. PRF activity in PP extracts from 10- and 20 day-old (d) rats was very low, increased gradually in 30d and 40d rats, and remained unchanged in adult (90d) rats. In a second experiment, age-related changes in anterior pituitary responsiveness to PP extracts from adult rats and to TRH were determined. The responsiveness of anterior pituitary cells from 10d rats to PRF was low, increased dramatically in cells from 20d rats, and was reduced in cells from 30d and adult rats. The responsiveness to TRH was highest in cells from 10d rats. In a third experiment, anterior pituitary responsiveness to age-matched PP extracts was assessed. Only PIF activity was observed when PP extracts from 10d rats were incubated with anterior pituitary cells from 10d rats. In contrast, PP extracts from 20d, 30d and adult rats exhibited only PRF activity when incubated with age-matched cells.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
992.
993.
Stephen A. Spencer Cortland Linder James M. StJ. Penney Hannah J. Russell Kate Hyde Caitlin Sheehy Alice Reid Emmanuel H. Andriamasy Gina U. Raderalazasoa Daniel A. L. Rakotomampianina Anjara M. Nandimbiniaina Tahiry N. Ranaivoson Antsa Andrianiaina Sheena M. Cruickshank Amaya L. Bustinduy J. Russell Stothard Glenn T. Edosoa Alain M. Rahetilahy 《The American journal of tropical medicine and hygiene》2021,104(5):1841
994.
The human GH-releasing hormone (hGHRH) transgenic mouse has a hyperplastic anterior pituitary gland that eventually develops into an adenoma. We showed previously that the number of lactotrophs in the male hGHRH transgenic mouse is increased 2-fold, yet there is no concomitant increase in plasma levels of PRL. To further elucidate underlying changes in lactotroph function in the hGHRH transgenic mouse, the objectives of this study were to 1) examine the relative differences in PRL gene expression in transgenic mice and their siblings, 2) quantify PRL secretion at the level of the individual cell, 3) determine whether tyrosine hydroxylase gene expression and/or activity are altered in the hypothalamus of transgenic mice, and 4) assess dopamine receptor gene expression and functional sensitivity in lactotrophs of transgenic mice. Total PRL messenger RNA (mRNA) levels were increased nearly 5-fold in the hGHRH transgenic mouse, whereas the concentrations of PRL mRNA (PRL mRNA per microg total RNA) were unchanged. In contrast, total PRL contents were unchanged, whereas the concentrations of PRL (micrograms of PRL per mg total protein) were decreased 3-fold. Hypothalamic tyrosine hydroxylase steady state mRNA levels were not altered in the hGHRH transgenic mice, but hypothalamic tyrosine hydroxylase activity was increased 2-fold in transgenic mice. Dopamine D2 receptor mRNA concentrations in the anterior pituitary were increased 2.5-fold in hGHRH transgenic mice, and total pituitary D2 receptor mRNA levels were increased nearly 10-fold. Furthermore, the basal secretory capacity of lactotrophs from transgenic mice was increased significantly at the level of the single cell, and dopamine inhibited the secretion of PRL to a greater extent in hGHRH transgenic mice. Thus, although the total number of lactotrophs is increased 2-fold in hGHRH transgenic mice, the present data are consistent with the hypothesis that increased hypothalamic dopamine synthesis and release coupled with an increase in D2 dopamine receptor gene expression and functional sensitivity in the pituitary result in normal plasma levels of PRL. 相似文献
995.
Estradiol attenuates the forskolin-induced increase in hypothalamic tyrosine hydroxylase activity 总被引:6,自引:0,他引:6
The purpose of this study was to evaluate interactions between estradiol and the 3',5' cyclic adenosine monophosphate (cAMP) signaling pathway to regulate tyrosine hydroxylase (TH) activity in hypothalamic dopaminergic neurons. The first experiment examined the ability of forskolin to activate TH in the tuberoinfundibular dopaminergic neurons of adult ovariectomized rats with or without estradiol treatment. Estradiol treatment reduced both basal and forskolin-stimulated TH activity in the median eminence. The second group of experiments examined the effect of estradiol on the forskolin-induced activation of TH in fetal hypothalamic cells cultures. Estradiol decreased basal TH activity in the hypothalamic cell cultures to 80% of control levels. Forskolin treatment for 1 h increased TH activity in a concentration-dependent manner in control and estradiol-treated cells, but estradiol attenuated the stimulatory response to 0.01-10 microM forskolin. The suppressive effect of estradiol on cAMP-dependent activation of TH was evident with 1-12 h of forskolin treatment. The responses to other activators of the cAMP- protein kinase A pathway, including dibutyryl cAMP and 8-bromo-cAMP, and to a depolarizing stimulus were blunted in estradiol-treated cultures. Forskolin treatment for 1 h increased radiolabeled phosphate incorporation into TH protein in control but not estradiol-treated cells, suggesting that estradiol interferes with the ability of the cAMP pathway to phosphorylate TH. Forskolin caused a time-dependent increase in TH mRNA signal levels in control cultures. The magnitude of the forskolin-induced increase in TH mRNA levels was less in the estradiol-treated cells after 6 h of forskolin treatment, indicating that estradiol hinders cAMP-regulated TH gene expression. These data indicate that estradiol attenuates the ability of hypothalamic dopaminergic neurons to respond to cAMP-dependent stimulation by interfering with phosphorylation mechanisms in the short term and control of TH mRNA levels in the long term. 相似文献
996.
Clete A. Kushida M.D. Ph.D. Deborah A. Nichols M.S. Richard D. Simon M.D. Terry Young M.D. John H. Grauke M.D. J. B. Britzmann M.D. Pamela R. Hyde M.A. William C. Dement M.D. Ph.D. 《Sleep & breathing》2000,4(1):11-15
The prevalence of sleep disorders in a primary care physician practice in Moscow, Idaho, was studied between February 7, 1997, and February 6, 1998. This primary care clinic visit population was surveyed for this 1-year period. Every patient above the age of 18 years who visited the Moscow Clinic in this time period was either approached by our on-site researcher during the patients clinic visit or contacted via mail. Out of a total of 1249 adult patients who met with our on-site researcher during their clinic visit, 962 (77.0%) completed questionnaires and were interviewed for symptoms of sleep disorders. An additional 292 patients completed mailed questionnaires, resulting in a total of 1254 participants in the study. The percentages of patients in our sample reporting symptoms of the following sleep disorders were insomnia (32.3%), obstructive sleep apnea syndrome (23.6%), and restless legs syndrome (29.3%). This study demonstrates the need for heightened awareness and subsequent diagnosis and treatment of sleep disorders in the primary care population. 相似文献
997.
Robert E. Goldstein Laurence C. Corash John F. Tallman C.Raymond Lake John Hyde Craig C. Smith Norine L. Capurro Judith C. Anderson 《The American journal of cardiology》1981,47(5):1115-1122
Although clinical observations suggest that abrupt discontinuation of propranolol therapy may precipitate myocardial ischemia and infarction in patients with coronary occlusive disease, the physiologic consequences of propranolol withdrawal are not fully understood. Platelet survival times and heart rate responses to exercise, upright tilt and isoproterenol were therefore examined in 14 normal subjects before and after abrupt withdrawal of propranolol. Propranolol, 80 to 240 mg/day, was given for 24 to 79 days; its effect was confirmed by a lower heart rate during exercise and during infusion of isoproterenol. In 10 subjects, the mean survival time of chromium-51-tagged blood platelets decreased from 10.0 days before propranolol to 7.8 days after its withdrawal (p <0.05). One day after withdrawal, the rise in heart rate with exercise or tilt was slightly increased from values before propranolol therapy. Two days after withdrawal of propranolol the mean peak heart rate during exercise (165 beats/min) was 12 beats/min higher (p <0.01) than the value before propranolol. On this same day heart rate increased more after tilt without medication (+6 beats/min, p <0.05) and more after tilt following vagal blockade (+8 beats/min, p <0.02) than before treatment with propranolol. Seven days after propranolol withdrawal, heart rate responses to exercise or tilt remained increased. Isoproterenol-induced heart rate responses (5 to 40 ng/kg per min, n = 14), white blood cell beta receptor function (cyclic adenosine monophosphate production after isoproterenol and 3H-I-dihydroalprenolol binding, n = 9) and plasma norepinephrine values at rest and during exercise (n = 7) were each unaltered after propranolol.The results suggest that abrupt withdrawal of propranolol is accompanied by a shortening of platelet survival and enhancement of sympathetically mediated reflex increases in heart rate. These changes may each play a role in the increased incidence of ischemic episodes observed after withdrawal of propranolol from patients with coronary occlusive disease. However, the number of beta receptors and their sensitivity to adrenergic agonists do not seem to be changed uniformly after abrupt withdrawal of propranolol. 相似文献
998.
Epithelial injury, inflammation, and repair in the hamster lung following intratracheal instillation of enzyme-generated oxidants 总被引:2,自引:0,他引:2
Oxidant-induced inflammatory and morphologic changes evoked by intratracheally instilled glucose, active glucose oxidase, and lactoperoxidase in hamsters are described. Similar solutions containing heat-denatured (DE) glucose oxidase served as a control treatment. During the 7-week post-treatment period, animals were sacrificed and lavaged, and their lungs were preserved for later study. Although a neutrophil-rich alveolitis was observed initially in both groups, the leukocytic influx and mild morphologic changes in DE-treated animals resolved within 7 days. In contrast, glucose oxidase mixtures caused necrotic alveolar epithelium, fibrin-like exudate, and significantly higher neutrophil and protein levels in bronchoalveolar lavage fluid (BALF) after 1 day. At 4 days, type II cell hyperplasia was extensive and BALF levels of all inflammatory cell types were significantly greater than BALF counts in DE animals. By 7 days, BALF macrophage and lymphocyte levels remained significantly elevated, and epithelial hyperplasia coincided with marked increases in lung hydroxyproline and interstitial cells. BALF parameters suggested that inflammation induced by glucose oxidase resolved within 15 days, yet total hydroxyproline levels remained elevated at 15 days and epithelial lesions were still detectable at 29 days. Oxidant-induced inflammation and epithelial injury were transient and preceded moderate collagen deposition. 相似文献
999.
Effect of Clostridium difficile toxin A on human intestinal epithelial cells: induction of interleukin 8 production and apoptosis after cell detachment. 总被引:6,自引:5,他引:6 下载免费PDF全文
Clostridium difficile is the aetiological agent of pseudomembranous colitis, and animal studies suggest the essential role of secreted toxin A in inducing disease. This study examined the biological responses to toxin A by human intestinal epithelial cells. Confluent monolayers of Caco2, HT29, and T84 cells and primary epithelial cells in organ cultures of human colonic biopsy specimens and after detachment with EDTA were studied. Interleukin 8 was assayed using enzyme linked immunosorbent assay (ELISA). Purified C difficile toxin A induced cell rounding and detachment of monolayers of the epithelial cell lines. Cells in detached monolayers initially remained viable while adherent to each other. Subsequently, an increasing number of apoptotic cells appeared in suspension. Exposure to toxin A for 24 hours induced interleukin 8 production in T84 and HT29 cells. Toxin A also induced epithelial cell rounding, detachment, and apoptosis in organ cultures of human colonic biopsy specimens. During culture (in medium only), EDTA detached colonic epithelial cells produced interleukin 8 and cell death occurred by apoptosis. Colonic disease by C difficile may be initiated by toxin A mediated induction of epithelial cell interleukin 8 production and apoptosis after cell detachment from the basement membrane. Studies on isolated (toxin untreated) colonic epithelial cells suggest that interleukin 8 production and apoptosis occur as a consequence of cell injury and detachment. 相似文献
1000.
Arkin MR Randal M DeLano WL Hyde J Luong TN Oslob JD Raphael DR Taylor L Wang J McDowell RS Wells JA Braisted AC 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(4):1603-1608
Understanding binding properties at protein-protein interfaces has been limited to structural and mutational analyses of natural binding partners or small peptides identified by phage display. Here, we present a high-resolution analysis of a nonpeptidyl small molecule, previously discovered by medicinal chemistry [Tilley, J. W., et al. (1997) J. Am. Chem. Soc. 119, 7589-7590], which binds to the cytokine IL-2. The small molecule binds to the same site that binds the IL-2 alpha receptor and buries into a groove not seen in the free structure of IL-2. Comparison of the bound and several free structures shows this site to be composed of two subsites: one is rigid, and the other is highly adaptive. Thermodynamic data suggest the energy barriers between these conformations are low. The subsites were dissected by using a site-directed screening method called tethering, in which small fragments were captured by disulfide interchange with cysteines introduced into IL-2 around these subsites. X-ray structures with the tethered fragments show that the subsite-binding interactions are similar to those observed with the original small molecule. Moreover, the adaptive subsite tethered many more compounds than did the rigid one. Thus, the adaptive nature of a protein-protein interface provides sites for small molecules to bind and underscores the challenge of applying structure-based design strategies that cannot accurately predict a dynamic protein surface. 相似文献