Science.gov

Sample records for acth adrenocorticotropic hormone

  1. ACTH (Adrenocorticotropic Hormone) Test

    MedlinePlus

    ... disease and ectopic ACTH from cortisol and ACTH measurement alone. A variety of other tests are often ... as any steroid, oral, inhaled, topical or eye drop may cause abnormal results. Megestrol acetate can also ...

  2. 21 CFR 862.1025 - Adrenocorticotropic hormone (ACTH) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Adrenocorticotropic hormone (ACTH) test system. 862.1025 Section 862.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  3. 21 CFR 862.1025 - Adrenocorticotropic hormone (ACTH) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Adrenocorticotropic hormone (ACTH) test system. 862.1025 Section 862.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  4. 21 CFR 862.1025 - Adrenocorticotropic hormone (ACTH) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Adrenocorticotropic hormone (ACTH) test system. 862.1025 Section 862.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  5. 21 CFR 862.1025 - Adrenocorticotropic hormone (ACTH) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Adrenocorticotropic hormone (ACTH) test system. 862.1025 Section 862.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  6. 21 CFR 862.1025 - Adrenocorticotropic hormone (ACTH) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Adrenocorticotropic hormone (ACTH) test system. 862.1025 Section 862.1025 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical...

  7. Topiramate and adrenocorticotropic hormone (ACTH) as initial treatment for infantile spasms.

    PubMed

    Peltzer, Bradley; Alonso, William D; Porter, Brenda E

    2009-04-01

    Historically, adrenocorticotropic hormone was used as a first-line treatment for infantile spasms; however, there has been increasing use of topiramate as initial therapy. Here, we report a retrospective study of adrenocorticotropic hormone (ACTH) and topiramate as initial treatment for infantile spasms. The neurology patient database at the Children's Hospital of Philadelphia was searched using the International Classification of Diseases, Ninth Revision code for infantile spasms, and 50 patients were randomly chosen for chart review. We identified 31 patients receiving either adrenocorticotropic hormone or topiramate monotherapy (adrenocorticotropic hormone n = 12, topiramate n = 19) as a first-line treatment for infantile spasms. A total of 26 patients were symptomatic and 5 cryptogenic. Six patients treated with adrenocorticotropic hormone had resolution of clinical spasms and hypsarrhythmia within a month, but 3 relapsed. Of the 19 patients treated with topiramate, 4 patients eventually, though over a period of 0, 1, 8, or 69 months, had resolution of spasms and hypsarrhythmia.

  8. Metastatic Pancreatic Neuroendocrine Tumor that Progressed to Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome with Growth Hormone-releasing Hormone (GHRH) Production

    PubMed Central

    Tadokoro, Rie; Sato, Shotaro; Otsuka, Fumiko; Ueno, Makoto; Ohkawa, Shinichi; Katakami, Hideki; Taniyama, Matsuo; Nagasaka, Shoichiro

    2016-01-01

    The patient was a 61-year-old woman who had a well-differentiated pancreatic neuroendocrine tumor (PNET) with lymph node metastasis. After 15 months of octreotide treatment, glucose control deteriorated and pigmentation of the tongue and moon face developed, leading to the diagnosis of ectopic adrenocorticotropic hormone (ACTH) syndrome. An abnormal secretion of growth hormone (GH) was identified, and the plasma growth hormone-releasing hormone (GHRH) level was elevated. A tumor biopsy specimen positively immunostained for ACTH and GHRH. Ectopic hormone secretion seems to have evolved along with the progression of the PNET. PMID:27746436

  9. Metastatic Pancreatic Neuroendocrine Tumor that Progressed to Ectopic Adrenocorticotropic Hormone (ACTH) Syndrome with Growth Hormone-releasing Hormone (GHRH) Production.

    PubMed

    Tadokoro, Rie; Sato, Shotaro; Otsuka, Fumiko; Ueno, Makoto; Ohkawa, Shinichi; Katakami, Hideki; Taniyama, Matsuo; Nagasaka, Shoichiro

    The patient was a 61-year-old woman who had a well-differentiated pancreatic neuroendocrine tumor (PNET) with lymph node metastasis. After 15 months of octreotide treatment, glucose control deteriorated and pigmentation of the tongue and moon face developed, leading to the diagnosis of ectopic adrenocorticotropic hormone (ACTH) syndrome. An abnormal secretion of growth hormone (GH) was identified, and the plasma growth hormone-releasing hormone (GHRH) level was elevated. A tumor biopsy specimen positively immunostained for ACTH and GHRH. Ectopic hormone secretion seems to have evolved along with the progression of the PNET.

  10. Effect of adrenocorticotropic hormone (ACTH) and insulin on the phagocytic capacity of Tetrahymena.

    PubMed

    Köhidai, L; Lovas, B; Csaba, G

    1995-06-01

    Adrenocorticotropic hormone (ACTH) and insulin negatively influenced the phagocytic activity of Tetrahymena. The two hormones had diverse effects after 4 hr of treatments on no-test-particle containing, "0-cells". At this time the number of "0 cells" was significantly lower in the ACTH-treated groups, while in the insulin-treated groups there was an increase of "0-cells" compared to the control and to the results of the starting experiment. Considering previous results, when small molecular weight hormones, if did at all, positively influenced phagocytosis in Tetrahymena, the experiments call the attention to the differences caused by the size of the signal molecules. In the light of the literary data on hormone effects to phagocytosis in mammals and men, the similarity of the effects in species being very far from each other in evolution, could be concluded.

  11. Differential responses of cortisol and corticosterone to adrenocorticotropic hormone (ACTH) in a subterranean rodent (Ctenomys talarum).

    PubMed

    Vera, Federico; Zenuto, Roxana Rita; Antenucci, Carlos Daniel

    2012-03-01

    We aimed to evaluate the responses of cortisol, corticosterone, and blood glucose to adrenocorticotropic hormone (ACTH) in males and females of the subterranean rodent Ctenomys talarum and addressed interannual variations in the plasma levels of both hormones. The most important results indicate that: (1) cortisol positively responds to the ACTH signal but corticosterone does not, even though corticosterone levels were higher than cortisol concentrations, (2) plasma corticosterone concentrations in free-living animals were 20 times higher compared to values reported for the same population during previous annual periods and, as cortisol levels were similar, this resulted in much lower cortisol/corticosterone ratios, (3) cortisol and corticosterone differentiated in their relative proportions in plasma in free-living males and females. These results indicate that cortisol and corticosterone are differentially regulated in our study species and emphasize that a remarkable temporal variation in the relative proportions of these hormones may occur in natural populations. Therefore, the conclusions regarding the presence of cortisol and corticosterone in plasma of wild animals may differ substantially depending on the moment when the study is conducted. Recent data indicate that cortisol and corticosterone are not interchangeable hormones in species of free-living vertebrates. We suggest that, in addition to the classical roles of glucocorticoids (GCs), it is crucial that other physiological functions be kept in mind when interpreting GC data from wild species.

  12. Do Patients Require Inpatient Admission to Receive Adrenocorticotropic Hormone (ACTH)? A Survey of US-Based Prescribers.

    PubMed

    Joshi, Charuta; Berg, Anne T; Wirrell, Elaine

    2016-02-01

    We aimed to determine variation in treatment of newly diagnosed infantile spasms, focusing on details of adrenocorticotropic hormone (ACTH) administration using a Redcap questionnaire sent to members of the Child Neurology Society. Two hundred fifty-seven members responded. Eighty-four percent prescribers used ACTH to treat infantile spasms. Seventy-six percent always admit patients. There is no difference between prescriber type (epileptologist or other) and prescriber location (state-funded or non-state-funded hospital) for decision to admit. Electroencephalographic (EEG) confirmation of spasms and education for injection were the commonest reasons to admit. Only 45% of prescribers accurately estimated the cost of ACTH. Participants in the hospital vial program were significantly more likely to always admit patients for ACTH than those who did not participate in such a program (P = .02). Although having the hospital sample vial allows time to complete investigation of infantile spasms and eliminates delays in initiating ACTH, it adds significantly to the cost of therapy.

  13. Direct activating effects of adrenocorticotropic hormone (ACTH) on brown adipose tissue are attenuated by corticosterone.

    PubMed

    van den Beukel, Johanna C; Grefhorst, Aldo; Quarta, Carmelo; Steenbergen, Jacobie; Mastroberardino, Pier G; Lombès, Marc; Delhanty, Patric J; Mazza, Roberta; Pagotto, Uberto; van der Lely, Aart Jan; Themmen, Axel P N

    2014-11-01

    Brown adipose tissue (BAT) and brown-like cells in white adipose tissue (WAT) can dissipate energy through thermogenesis, a process mediated by uncoupling protein 1 (UCP1). We investigated whether stress hormones ACTH and corticosterone contribute to BAT activation and browning of WAT. ACTH and corticosterone were studied in male mice exposed to 4 or 23°C for 24 h. Direct effects were studied in T37i mouse brown adipocytes and primary cultured murine BAT and inguinal WAT (iWAT) cells. In vivo effects were studied using (18)F-deoxyglucose positron emission tomography. Cold exposure doubled serum ACTH concentrations (P=0.03) and fecal corticosterone excretion (P=0.008). In T37i cells, ACTH dose-dependently increased Ucp1 mRNA (EC50=1.8 nM) but also induced Ucp1 protein content 88% (P=0.02), glycerol release 32% (P=0.03) and uncoupled respiration 40% (P=0.003). In cultured BAT and iWAT, ACTH elevated Ucp1 mRNA by 3-fold (P=0.03) and 3.7-fold (P=0.01), respectively. In T37i cells, corticosterone prevented induction of Ucp1 mRNA and Ucp1 protein by both ACTH and norepinephrine in a glucocorticoid receptor (GR)-dependent fashion. ACTH and GR antagonist RU486 independently doubled BAT (18)F-deoxyglucose uptake (P=0.0003 and P=0.004, respectively) in vivo. Our results show that ACTH activates BAT and browning of WAT while corticosterone counteracts this.

  14. Metabolic responses to adrenocorticotropic hormone (ACTH) vary with life-history stage in adult male northern elephant seals.

    PubMed

    Ensminger, David C; Somo, Derek A; Houser, Dorian S; Crocker, Daniel E

    2014-08-01

    Strong individual and life-history variation in serum glucocorticoids has been documented in many wildlife species. Less is known about variation in hypothalamic-pituitary-adrenal (HPA) axis responsiveness and its impact on metabolism. We challenged 18 free-ranging adult male northern elephant seals (NES) with an intramuscular injection of slow-release adrenocorticotropic hormone (ACTH) over 3 sample periods: early in the breeding season, after 70+ days of the breeding fast, and during peak molt. Subjects were blood sampled every 30 min for 2h post-injection. Breeding animals were recaptured and sampled at 48 h. In response to the ACTH injection, cortisol increased 4-6-fold in all groups, and remained elevated at 48 h in early breeding subjects. ACTH was a strong secretagogue for aldosterone, causing a 3-8-fold increase in concentration. Cortisol and aldosterone responses did not vary between groups but were correlated within individuals. The ACTH challenge produced elevations in plasma glucose during late breeding and molting, suppressed testosterone and thyroid hormone at 48 h in early breeding, and increased plasma non-esterified fatty acids and ketoacids during molting. These data suggest that sensitivity of the HPA axis is maintained but the metabolic impacts of cortisol and feedback inhibition of the axis vary with life history stage. Strong impacts on testosterone and thyroid hormone suggest the importance of maintaining low cortisol levels during the breeding fast. These data suggest that metabolic adaptations to extended fasting in NES include alterations in tissue responses to hormones that mitigate deleterious impacts of acute or moderately sustained stress responses.

  15. Variability in leptin and adrenal response in juvenile Steller sea lions (Eumetopias jubatus) to adrenocorticotropic hormone (ACTH) in different seasons.

    PubMed

    Mashburn, Kendall L; Atkinson, Shannon

    2008-01-15

    Eight free-ranging juvenile Steller sea lions (SSL; 6 males, 2 females; 14-20 months) temporarily held under ambient conditions at the Alaska SeaLife Center were physiologically challenged through exogenous administration of adrenocorticotropic hormone (ACTH). Four individuals (3 males, 1 female) underwent ACTH challenge in each of two seasons, summer and winter. Following ACTH injection serial blood and fecal samples were collected for up to 3 and 96 h, respectively. A radioimmunoassay (RIA) was validated for leptin, and using a previously validated RIA for cortisol, collected sera were analyzed for both cortisol and leptin. ACTH injection resulted in a 2.9-fold increase (P=0.164) in leptin which preceded a 3.2-fold increase (P=0.0290) in cortisol by 105 min in summer. In winter, a 1.7-fold increase in leptin (P=0.020) preceded a 2.1-fold increase (P=0.001) in serum cortisol by 45 min. Mean fecal corticosteroid maxima were 10.4 and 16.7-fold above baseline 28 and 12 h post-injection and returned to baseline 52 and 32 h post-injection, in summer and winter, respectively. Data indicate acute activity in juvenile adrenal glands is detectable in feces approximately 12-24 h post-stimulus in either season, with a duration of approximately 40 h in summer and 20 h in winter. Changes in serum cortisol proved statistically significant both seasons and elevated concentrations were detected by 30 min post-stimulus (baseline 64.8+/-4.2; peak 209.5+/-18.3 ng/ml: summer; baseline 87.0+/-15.7; peak 237.6+/-10.0 ng/ml: winter), whereas the changes that occurred in serum leptin proved to be significant only in winter (baseline 6.4+/-0.6; peak 18.7+/-7.0 ng/ml: summer; baseline 4.2+/-0.5; peak 7.5+/-0.6 ng/ml: winter). Changes in fecal corticosteroids proved significant only in summer (baseline 117.8+/-36.7; peak 1219.3+/-298.4 ng/g, P=0.038: summer; baseline 71.8+/-13.7; peak 1198.6+/-369.9 ng/g, P=0.053: winter) due to a high degree of individual variability in winter months. The

  16. Effects of benzyl glucoside and chlorogenic acid from Prunus mume on adrenocorticotropic hormone (ACTH) and catecholamine levels in plasma of experimental menopausal model rats.

    PubMed

    Ina, Hiroji; Yamada, Kenji; Matsumoto, Kosai; Miyazaki, Toshio

    2004-01-01

    To investigate the effectiveness of benzyl beta-D-glucopyranoside (BG) and chlorogenic acid (CA), the constituents of the fruit of Prunus mume, for relieving tension in experimental menopausal model rats (M-rats) caused by ether stress, the effects of BG and CA on adrenocorticotropic hormone (ACTH) and catecholamine (adrenaline, noradrenaline, and dopamine) levels were examined in the plasma of M-rats. Caffeic acid, quinic acid, and rosmarinic acid, which are compounds structurally related to CA, were also examined. BG obviously recovered catecholamine levels decreased by ether stress and increased dopamine to high levels. On the other hand, CA significantly decreased the ACTH level increased by ether stress and showed the greatest effect of all compounds. These results suggest that BG and CA may contribute to relieving the tension in M-rats caused by ether stress.

  17. CXCL10/CXCR3 signaling mediates inhibitory action by interferon-gamma on CRF-stimulated adrenocorticotropic hormone (ACTH) release.

    PubMed

    Horiguchi, Kotaro; Fujiwara, Ken; Tsukada, Takehiro; Yoshida, Saishu; Higuchi, Masashi; Tateno, Kozue; Hasegawa, Rumi; Takigami, Shu; Ohsako, Shunji; Yashiro, Takashi; Kato, Takako; Kato, Yukio

    2016-05-01

    Secretion of hormones by the anterior pituitary gland can be stimulated or inhibited by paracrine factors that are produced during inflammatory reactions. The inflammation cytokine interferon-gamma (IFN-γ) is known to inhibit corticotropin-releasing factor (CRF)-stimulated adrenocorticotropin (ACTH) release but its signaling mechanism is not yet known. Using rat anterior pituitary, we previously demonstrated that the CXC chemokine ligand 10 (CXCL10), known as interferon-γ (IFN-γ) inducible protein 10 kDa, is expressed in dendritic cell-like S100β protein-positive (DC-like S100β-positive) cells and that its receptor CXCR3 is expressed in ACTH-producing cells. DC-like S100β-positive cells are a subpopulation of folliculo-stellate cells in the anterior pituitary. In the present study, we examine whether CXCL10/CXCR3 signaling between DC-like S100β-positive cells and ACTH-producing cells mediates inhibition of CRF-activated ACTH-release by IFN-γ, using a CXCR3 antagonist in the primary pituitary cell culture. We found that IFN-γ up-regulated Cxcl10 expression via JAK/STAT signaling and proopiomelanocortin (Pomc) expression, while we reconfirmed that IFN-γ inhibits CRF-stimulated ACTH-release. Next, we used a CXCR3 agonist in primary culture to analyze whether CXCL10 induces Pomc-expression and ACTH-release using a CXCR3 agonist in the primary culture. The CXCR3 agonist significantly stimulated Pomc-expression and inhibited CRF-induced ACTH-release, while ACTH-release in the absence of CRF did not change. Thus, the present study leads us to an assumption that CXCL10/CXCR3 signaling mediates inhibition of the CRF-stimulated ACTH-release by IFN-γ. Our findings bring us to an assumption that CXCL10 from DC-like S100β-positive cells acts as a local modulator of ACTH-release during inflammation.

  18. Long-term bioeffects of 435-MHz radiofrequency radiation on selected blood-borne endpoints in cannulated rats. Volume 2. Plasma ACTH (adrenocorticotropic hormone) and plasma corticosterone. Final report, 20 August 1984-16 February 1986

    SciTech Connect

    Popovic, V.P.; Toler, J.C.; Bonasera, S.J.; Popovic, P.P.; Honeycutt, C.B.

    1987-08-01

    Two hundred adult male white rats with chronically implanted aortic cannulas were randomly divided into two groups. Animals in the first group were exposed to low-level (1.0 mW/cm2) pulsed-wave 435-MHz radiofrequency radiation (RFR) for approximately 22 h daily, 7 days each week, for 6 months. Animals in the second group were maintained under identical conditions, but were not radiated. The cannulas were used to draw microsamples (0.3 mL) of aortic blood from the unrestrained, unanesthetized rats on a cyclic schedule. Plasma adrenocorticotropic hormone (ACTH) and plasma corticosterone concentrations were determined by radioimmunoassays hormone (ACTH) and plasma corticosterone concentrations were determined by radioimmunoassays. Statistical analysis of the results did not indicate increased plasma ACTH and plasma corticosterone concentrations in exposed animals when compared to sham-exposed animals. Exposure to this low-level radiofrequency environment did not induce stresses that were manifested as an alteration in plasma hormones.

  19. Radioactive probes for adrenocorticotropic hormone receptors

    SciTech Connect

    Hofmann, K.; Romovacek, H.; Stehle, C.J.; Finn, F.M.; Bothner-By, A.A.; Mishra, P.K.

    1986-03-25

    Our attempts to develop adrenocorticotropic hormone (ACTH) analogues that can be employed for ACTH receptor identification and isolation began with the synthesis of ACTH fragments containing N epsilon-(dethiobiotinyl)lysine (dethiobiocytin) amide in position 25 to be used for affinity chromatographic purification of hormone-receptor complexes on Sepharose-immobilized avidin resins. Because labeling ACTH or ACTH fragments by conventional iodination techniques destroys biological activity due to oxidation of Met4 and incorporation of iodine into Tyr2, we have prepared (Phe2,Nle4)ACTH1-24, (Phe2,Nle4,biocytin25)ACTH1-25 amide, and (Phe2,Nle4,dethiobiocytin25)ACTH1-25 amide by conventional synthetic techniques. The HPLC profiles and amino acid analyses of the final products indicate that the materials are of a high degree of purity. The amount of tertiary butylation of the Trp residue in the peptides was assessed by NMR and was found to be less than 0.5%. All three peptides are equipotent with the standard ACTH1-24 as concerns their ability to stimulate steroidogenesis and cAMP formation in bovine adrenal cortical cells. Iodination of (Phe2,Nle4)ACTH1-24, with iodogen as the oxidizing agent, has been accomplished without any detectable loss of biological activity. The mono- and diiodo derivatives of (Phe2,Nle4)ACTH1-24 have been prepared, separated by HPLC, and assayed for biological activity. Both peptides have the full capacity to stimulate steroidogenesis and cAMP production in bovine adrenal cortical cells.

  20. Effects of inhaling the vapor of Lavandula burnatii super-derived essential oil and linalool on plasma adrenocorticotropic hormone (ACTH), catecholamine and gonadotropin levels in experimental menopausal female rats.

    PubMed

    Yamada, Kenji; Mimaki, Yoshihiro; Sashida, Yutaka

    2005-02-01

    The effects of inhaling the vapor of Lavandula burnatii super-derived essential oil and one of the main components of lavender oil, linalool on plasma adrenocorticotropic hormone (ACTH), catecholamine and gonadotropin levels in menopausal model rats under ether-inhalation were studied. The increased plasma ACTH levels induced by ether-inhalation tended to decrease by pre-inhalation of Lavandula burnetii super and linalool vapor was induced the decrease of ACTH level. The decrease in adrenaline, noradrenaline and dopamine levels induced by ether-inhalation tended to recover, especially, the dopamine level significantly recovered to the normal level by the inhalation of Lavandula burnetii super and linalool vapor. However, the increased plasma gonadotropin levels in ovariectomized retired female rats (menopausal model rats) was significantly decreased by the inhalation of linalool. These results suggest that lavender oil or one of the main components, linalool may contribute to relieving tension and may be applicable to the treatment of menopausal disorders in human beings.

  1. Plurihormonal pituitary adenoma with concomitant adrenocorticotropic hormone (ACTH) and growth hormone (GH) secretion: a report of two cases and review of the literature.

    PubMed

    Rasul, Fahid Tariq; Jaunmuktane, Zane; Khan, Akbar Ali; Phadke, Rahul; Powell, Michael

    2014-01-01

    Plurihormonal pituitary adenomas are tumours that show immunoreactivity for more than one hormone that cannot be explained by normal adenohypophysial cytodifferentiation. The most common combinations in these adenomas include growth hormone (GH), prolactin (PRL) and one or more glycoprotein hormone sub-units (β-TSH, β-FSH, β-LH and αSU). The authors report two cases of a plurihormonal pituitary adenoma expressing the rare combination of ACTH and GH. They both underwent successful transphenoidal hypophysectomy (TSH). Long-term post-operative follow-up revealed no evidence of tumour recurrence. Due to the multiple secretions and plurihormonal characteristics clinical diagnosis of composite pituitary adenomas can be difficult. The authors discuss the diagnosis and management of composite pituitary adenomas and review the literature regarding this rare phenomenon.

  2. Long-Term Bioeffects of 435MHz Radiofrequency Radiation on Selected Blood-Borne Endpoints in Cannulated Rats. Volume 2. Plasma ACTH (adrenocorticotropic Hormone) and Plasma Corticosterone

    DTIC Science & Technology

    1987-08-01

    stress hormone concentrations. In this study , an increase in plasma corticosterone was observed after barbiturate anesthesia (Fig. 5). Plasma ACTH...C.H., and Schindler, J. In vitro and vivo adrenal corticosterone secretion following stress. Am J Physiol 196:579-582 (1959). 16. Gale, G.C...related thereto. The animals involved in this study were procured, maintained, and used in accordance with the Animal Welfare Act and the "Guide for

  3. The orphan G protein-coupled receptor GPR139 is activated by the peptides: Adrenocorticotropic hormone (ACTH), α-, and β-melanocyte stimulating hormone (α-MSH, and β-MSH), and the conserved core motif HFRW.

    PubMed

    Nøhr, Anne Cathrine; Shehata, Mohamed A; Hauser, Alexander S; Isberg, Vignir; Mokrosinski, Jacek; Andersen, Kirsten B; Farooqi, I Sadaf; Pedersen, Daniel Sejer; Gloriam, David E; Bräuner-Osborne, Hans

    2017-01-01

    GPR139 is an orphan G protein-coupled receptor that is expressed primarily in the brain. Not much is known regarding the function of GPR139. Recently we have shown that GPR139 is activated by the amino acids l-tryptophan and l-phenylalanine (EC50 values of 220 μM and 320 μM, respectively), as well as di-peptides comprised of aromatic amino acids. This led us to hypothesize that GPR139 may be activated by peptides. Sequence alignment of the binding cavities of all class A GPCRs, revealed that the binding pocket of the melanocortin 4 receptor is similar to that of GPR139. Based on the chemogenomics principle "similar targets bind similar ligands", we tested three known endogenous melanocortin 4 receptor agonists; adrenocorticotropic hormone (ACTH) and α- and β-melanocyte stimulating hormone (α-MSH and β-MSH) on CHO-k1 cells stably expressing the human GPR139 in a Fluo-4 Ca(2+)-assay. All three peptides, as well as their conserved core motif HFRW, were found to activate GPR139 in the low micromolar range. Moreover, we found that peptides consisting of nine or ten N-terminal residues of α-MSH activate GPR139 in the submicromolar range. α-MSH1-9 was found to correspond to the product of a predicted cleavage site in the pre-pro-protein pro-opiomelanocortin (POMC). Our results demonstrate that GPR139 is a peptide receptor, activated by ACTH, α-MSH, β-MSH, the conserved core motif HFRW as well as a potential endogenous peptide α-MSH1-9. Further studies are needed to determine the functional relevance of GPR139 mediated signaling by these peptides.

  4. Medullary thyroid carcinoma with ectopic adrenocorticotropic hormone syndrome.

    PubMed

    Choi, Hong Seok; Kim, Min Joo; Moon, Chae Ho; Yoon, Jong Ho; Ku, Ha Ra; Kang, Geon Wook; Na, Im Il; Lee, Seung-Sook; Lee, Byung-Chul; Park, Young Joo; Kim, Hong Il; Ku, Yun Hyi

    2014-03-01

    Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.

  5. ACTH (cosyntropin) stimulation test

    MedlinePlus

    ... The ACTH stimulation test measures how well the adrenal glands respond to adrenocorticotropic hormone ( ACTH ). ACTH is a ... produced in the pituitary gland that stimulates the adrenal glands to release a hormone called cortisol. How the ...

  6. ACTH blood test

    MedlinePlus

    ... any time the skin is broken) Alternative Names Serum adrenocorticotropic hormone; Adrenocorticotropic hormone; Highly-sensitive ACTH Images Endocrine glands References Ferri FF. Cushing's disease and syndrome. In: Ferri FF, ed. Ferri's Clinical ...

  7. Adrenocorticotropic Hormone (ACTH) Responses Require Actions of the Melanocortin-2 Receptor Accessory Protein on the Extracellular Surface of the Plasma Membrane.

    PubMed

    Malik, Sundeep; Dolan, Terrance M; Maben, Zachary J; Hinkle, Patricia M

    2015-11-13

    The melanocortin-2 (MC2) receptor is a G protein-coupled receptor that mediates responses to ACTH. The MC2 receptor acts in concert with the MC2 receptor accessory protein (MRAP) that is absolutely required for ACTH binding and signaling. MRAP has a single transmembrane domain and forms a highly unusual antiparallel homodimer that is stably associated with MC2 receptors at the plasma membrane. Despite the physiological importance of the interaction between the MC2 receptor and MRAP, there is little understanding of how the accessory protein works. The dual topology of MRAP has made it impossible to determine whether highly conserved and necessary regions of MRAP are required on the intracellular or extracellular face of the plasma membrane. The strategy used here was to fix the orientation of two antiparallel MRAP molecules and then introduce inactivating mutations on one side of the membrane or the other. This was achieved by engineering proteins containing tandem copies of MRAP fused to the amino terminus of the MC2 receptor. The data firmly establish that only the extracellular amino terminus (Nout) copy of MRAP, oriented with critical segments on the extracellular side of the membrane, is essential. The transmembrane domain of MRAP is also required in only the Nout orientation. Finally, activity of MRAP-MRAP-MC2-receptor fusion proteins with inactivating mutations in either MRAP or the receptor was rescued by co-expression of free wild-type MRAP or free wild-type receptor. These results show that the basic MRAP-MRAP-receptor signaling unit forms higher order complexes and that these multimers signal.

  8. Positive gallium scan in the syndrome of opsoclonus-myoclonus treated with adrenocorticotropic hormone

    SciTech Connect

    Gumbinas, M.; Gratz, E.S.; Johnston, G.S.; Schwartz, A.D.

    1984-09-01

    The syndrome of opsoclonus and myoclonus may be the first presenting symptom of neuroblastoma. The disorder is often controlled by treatment with adrenocorticotropic hormone (ACTH). A child with this disorder and treated with ACTH gel had abnormal uptake of /sup 67/Ga in both adrenal glands during studies to attempt to detect an occult neuroblastoma. Repeat /sup 67/Ga scans proved to be normal once the ACTH was discontinued and the patient was treated with prednisone. It is concluded that ACTH stimulation of normal adrenal tissue was responsible for these abnormal findings.

  9. The influence od melatonin receptors antagonists, luzindole and 4-phenyl-2-propionamidotetralin (4-P-PDOT), on melatonin-dependent vasopressin and adrenocorticotropic hormone (ACTH) release from the rat hypothalamo-hypophysial system. In vitro and in vivo studies.

    PubMed

    Juszczak, M; Roszczyk, M; Kowalczyk, E; Stempniak, B

    2014-12-01

    Melatonin exerts its biological role acting via G protein-coupled membrane receptors - MT1 and MT2, as well as through cytoplasmic and/or nuclear receptors. Melatonin has previously been shown to change vasopressin (AVP) and adrenocorticotropic hormone (ACTH) secretion dependently on its concentration. To determine whether the response of vasopressinergic neurones to different concentrations of melatonin is mediated through the membrane MT1 and/or MT2 receptors, the influence of luzindole - an antagonist of both MT1 and MT2 receptors, and 4-phenyl-2-propionamidotetralin (4-P-PDOT) - a selective MT2 receptor antagonist, on melatonin-dependent AVP release from the rat hypothalamo-neurohypophysial (H-NH) system was studied in vitro (melatonin at the concentrations of 10(-9), 10(-7) and 10(-3) M) and in vivo (melatonin at the concentrations of 10(-9) and 10(-7) M). Moreover, the second goal of this study was to find out whether melatonin receptors MT1 and/or MT2 are involved in the regulation of ACTH and corticosterone secretion into the blood. We have demonstrated that melatonin, at the concentrations of 10(-9) and 10(-7) M, significantly inhibited AVP secretion from isolated rat H-NH explants when antagonists solvent (i.e. 0.1% DMSO) was present in the medium. Neither luzindole, nor 4-P-PDOT, applied without melatonin, did influence AVP release in vitro. Luzindole applied together with melatonin (10(-7) M and 10(-9) M) significantly suppressed melatonin-dependent effect, while 4-PPDOT did not eliminate the inhibitory influence of 10(-7) M and 10(-9) M melatonin on AVP secretion from isolated rat H-NH explants. Melatonin at a concentration of 10(-3) M significantly increased AVP release when the H-NH explants were incubated in the medium containing luzindole or 4-P-PDOT. Under present experimental in vivo conditions, infused intracerebroventricularly (i.c.v.) melatonin, at a concentration close to its physiological level in the blood, significantly diminished AVP

  10. Altered expression of adrenocorticotropic hormone in the epileptic gerbil hippocampus following spontaneous seizure.

    PubMed

    Oh, Yun-Jung; Kim, Heung-No; Jeong, Ji-Heon; Park, Dae-Kyoon; Park, Kyung-Ho; Ko, Jeong-Sik; Kim, Duk-Soo

    2013-02-01

    We investigated the temporal alterations of adrenocorticotropic hormone (ACTH) immunoreactivity in the hippocampus after seizure onset. Expression of ACTH was observed within interneurons in the pre-seizure group of seizure sensitive gerbils, whereas its immunoreactivities were rarely detected in seizure resistant gerbil. Three hr after the seizure, ACTH immunoreactivity was significantly increased in interneurons within all hippocampal regions. On the basis of their localization and morphology through immunofluorescence staining, these cells were identified as GABAA α1-containing interneurons. At the 12 hr postictal period, ACTH expression in these regions was down-regulated, in a similar manner to the pre-seizure group of gerbils. These findings support the increase in ACTH synthesis that contributes to a reduction of corticotrophin-releasing factor via the negative feedback system which in turn provides an opportunity to enhance the excitability of GABAergic interneurons. Therefore, ACTH may play an important role in the reduction of excitotoxicity in all hippocampal regions.

  11. Hormone (ACTH, T3) content of immunophenotyped lymphocyte subpopulations.

    PubMed

    Pállinger, Éva; Kiss, Gergely Attila; Csaba, György

    2016-12-01

    Cells of the immune system synthesize, store, and secrete polypeptide and amino acid type hormones, which also influence their functions, having receptors for different hormones. In the present experiment immunophenotyped immune cells isolated from bone marrow, thymus, and peritoneal fluid of mice were used for demonstrating the adrenocorticotropic hormone (ACTH) and triiodothyronine (T3) hormone production of differentiating immune cells. Both hormones were found in each cell type, and in each maturation state, which means that all cells are participating in the hormonal function of the immune system. The lineage-independent presence of ACTH and T3 in differentiating hematopoietic cells denotes that their expression ubiquitous during lymphocyte development. Higher ACTH and T3 content of B cells shows that these cells are the most hormonally active and suggests that the hormones may have an autocrine regulatory role in B cell development. Developing T cells showed heterogeneous hormone production which was associated with their maturation state. Differences in the hormone contents of immune cells isolated from different organs indicate that their hormone production is defined by their differentiation or maturation state, however, possibly also by the local microenvironment.

  12. Metastatic esthesioneuroblastoma secreting adrenocorticotropic hormone in pediatric patients.

    PubMed

    Galioto, Silvestre; Di Petrillo, Alessandro; Pastori, Mauro; Arecchi, Alberto

    2011-09-01

    The purpose of this article was to report a pediatric case of secondary cervical esthesioneuroblastoma involving the parapharyngeal lymph nodes. A 3-year-old boy came to our clinical observation because of a right lymphonodal mass evidenced by nuclear magnetic resonance and a diagnosis of Cushing syndrome associated with ectopic adrenocorticotropic hormone secretion, moon face, central obesity, asthenia, and hirsutism. At the age of 10 months, the patient underwent endoscopic surgery for asportation of the World Health Organization stage IV esthesioneuroblastoma. At 38 months of age, the patient underwent right parapharyngeal lymphadenectomy with surgical access by a double mandibulectomy. After surgery, serum ACTH, cortisolemia, and urinary excretion of cortisol were within the reference range. Blood pressure was recorded at 110/70 mm Hg. Moon face disappeared, as well as central obesity and hirsutism. Clinical report is presented together with brief review of literature.

  13. Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome

    PubMed Central

    KATO, AKIHISA; HAYASHI, KAZUKI; NAITOH, ITARU; SENO, KYOJI; OKADA, YUKIKO; BAN, TESSHIN; KONDO, HIROMU; NISHI, YUJI; UMEMURA, SHUICHIRO; HORI, YASUKI; NATSUME, MAKOTO; JOH, TAKASHI

    2016-01-01

    Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin. PMID:27330779

  14. Type 2 diabetes mellitus accompanied by isolated adrenocorticotropic hormone deficiency and gastric cancer.

    PubMed

    Kamiya, Yuji; Murakami, Masami

    2009-01-01

    A 69-year-old man with type 2 diabetes mellitus was admitted to our hospital because of appetite loss, nausea and vomiting. Gastroscopy revealed gastric cancer. Levels of plasma cortisol were decreased. Neither adrenocorticotropic hormone (ACTH) nor cortisol levels were adequately increased in response to a mixed intravenous administration of corticotropin-releasing hormone, growth hormone-releasing hormone, thyrotropin-releasing hormone and lutenizing hormone-releasing hormone, although other pituitary hormones were increased adequately. He was diagnosed as having isolated ACTH deficiency (IAD). Anti-pituitary antibody and anti-parietal cell antibody were positive. At least in part, these antibodies may play pathogenic roles of development of IAD and gastric cancer.

  15. [Ectopic Adrenocorticotropic Hormone-producing Pulmonary Carcinoid Tumor Presenting as Cushing Syndrome].

    PubMed

    Taniguchi, Daisuke; Sawada, Takahiro; Ebisui, Osamu; Kito, Katsumi; Nagayasu, Takeshi

    2015-02-01

    The patient was a 57-year-old female who felt muscle weakness and visited a physician. Hypokalemia was pointed out, and she was referred to our hospital for detailed examination and treatment. Hormone-related tests and imaging were performed, and the patient was diagnosed as Cushing syndrome. Moreover, an ectopic adrenocorticotropic hormone (ACTH)-producing tumor was suspected. The whole body was examined to find a tumor, but no apparent lesion was found, except for a small nodule of 5-mm in size was present in the right middle pulmonary lobe on chest computed tomography (CT). It was decided to perform surgical resection for both diagnosis and treatment. Pathological diagnosis was a typical carcinoid. On immunostaining, ACTH-positive cells were detected, and the lesion was definitely diagnosed as an ectopic ACTH-producing tumor. Since the ACTH level after surgery returned to normal, the lesion was concluded to be completely excised.

  16. Pubertal shifts in adrenal responsiveness to stress and adrenocorticotropic hormone in male rats.

    PubMed

    Romeo, Russell D; Minhas, Sumeet; Svirsky, Sarah E; Hall, Baila S; Savenkova, Marina; Karatsoreos, Ilia N

    2014-04-01

    Studies have indicated significant pubertal-related differences in hormonal stress reactivity. We report here that prepubertal (30 days) male rats display a more protracted stress-induced corticosterone response than adults (70 days), despite showing relatively similar levels of adrenocorticotropic hormone (ACTH). Additionally, we show that adrenal expression of the ACTH receptor, melanocortin 2 receptor (Mc2r), is higher in prepubertal compared to adult animals, and that expression of melanocortin receptor accessory protein (Mrap), a molecule that chaperones MC2R to the cell surface, is greater in prepubertal males following stress. Given that these data suggest a pubertal shift in adrenal sensitivity to ACTH, we directly tested this possibility by injecting prepubertal and adult males with 6.25 or 9.375μg/kg of exogenous rat ACTH and measured their hormone levels 30 and 60min post-injection. As these doses resulted in different circulating levels of ACTH at these two ages, we performed regression analyses to assess the relationship between circulating ACTH and corticosterone concentrations. We found no difference between the ages in the correlation between ACTH and corticosterone levels at the 30min time point. However, 60min following the ACTH injection, we found prepubertal rats had significantly higher corticosterone concentrations at lower levels of ACTH compared to adults. These data suggest that prolonged exposure to ACTH leads to greater corticosterone responsiveness prior to puberty, and indicate that changes in adrenal sensitivity to ACTH may, in part, contribute to the protracted hormonal stress response in prepubertal rats.

  17. Hypofibrinogenemia caused by adrenocorticotropic hormone for infantile spasms: a case report.

    PubMed

    Kamei, Atsushi; Araya, Nami; Akasaka, Manami; Mizuma, Kanako; Asami, Maya; Tanifuji, Sachiko; Chida, Shoichi

    2015-01-01

    We report the case of a 7-month-old boy who developed hypofibrinogenemia (66.6 mg/dL; reference value, 170-405 mg/dL) during adrenocorticotropic hormone (ACTH) therapy for infantile spasms. Although the patient showed no clinical signs of a bleeding diathesis, we recommend that plasma fibrinogen levels should be monitored during ACTH therapy, which should be discontinued when fibrinogen levels fall below hemostatic levels (60.0mg/dL) or when bleeding tendencies are recognized.

  18. Ectopic Adrenocorticotropic Hormone-Secreting Bronchial Carcinoid Diagnosed by Balloon-Occluded Pulmonary Arterial Sampling.

    PubMed

    Yotsukura, Masaya; Kohno, Mitsutomo; Asakura, Keisuke; Kamiyama, Ikuo; Ohtsuka, Takashi; Hayashi, Yuichiro; Kurihara, Isao; Nakatsuka, Seishi; Asamura, Hisao

    2016-05-01

    We present the case of a 50-year-old man with Cushing syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-secreting tumor. A small nodule was located in close association with the lateral segmental branch of the pulmonary artery in the left upper lobe. Blood samples were obtained from various branches of the pulmonary artery by balloon-occluded retrograde sampling for the measurement of location-specific serum ACTH levels. After confirmation that the pulmonary nodule was responsible for the increased ACTH secretion, lobectomy was performed. This report demonstrates the usefulness of balloon-occluded retrograde pulmonary arterial sampling for the preoperative diagnosis of an ACTH-producing tumor whose diagnosis is difficult to confirm.

  19. Cardiac Autonomic Dysfunction in Patients With Infantile Spasm and the Effect of Adrenocorticotropic Hormone Treatment.

    PubMed

    Gencpinar, Pinar; Kocabas, Abdullah; Duman, Özgür; Dündar, Nihal Olgaç; Haspolat, Senay; Kardelen, Fırat

    2016-02-01

    Infantile spasm is an age-dependent epileptic-encephalopathy syndrome. Cardiac autonomic function is frequently altered in epilepsy. In this study, we examined heart rate variability in patients with infantile spasm before and after treatment. Nineteen patients with infantile spasm and 13 healthy comparisons were enrolled in the study. Cardiac rhythm was recorded with a Holter device for 24 hours before adrenocorticotropic hormone (ACTH) (Synacthen depot) and B6 vitamin administration and 1 month after treatment. Heart rate variability analysis found lower heart rate variability parameters in patients with infantile spasm at the onset of the syndrome, prior to treatment with ACTH. The time domain parameters of heart rate variability values showed a statistically significant increase following ACTH treatment. Our data suggest that patients with infantile spasm exhibit lower heart rate variability parameters, and the treatment of spasms with ACTH and B6 together diminished the autonomic dysfunction in our cohort.

  20. Legionella pneumophila and Pneumocystis jirovecii coinfection in an infant treated with adrenocorticotropic hormone for infantile spasm: case report and literature review.

    PubMed

    Musallam, Nadira; Bamberger, Ellen; Srugo, Isaac; Dabbah, Husein; Glikman, Daniel; Zonis, Zeev; Kessel, Aharon; Genizi, Jacob

    2014-02-01

    We describe an 8-month-old infant with infantile spasms treated with adrenocorticotropic hormone (ACTH) who presented with fatal Legionella pneumophila and Pneumocystis jirovecii infection. Emphasis is placed on the ensuing immunosuppression and infectious sequelae of ACTH therapy. Given that ACTH therapy may increase the risk of fatal infection, patients undergoing such treatment should be closely monitored, with particular attention paid to the functioning of the immune system.

  1. Comparison of Ultraviolet Photodissociation and Collision Induced Dissociation of Adrenocorticotropic Hormone Peptides

    NASA Astrophysics Data System (ADS)

    Robotham, Scott A.; Brodbelt, Jennifer S.

    2015-09-01

    In an effort to better characterize the fragmentation pathways promoted by ultraviolet photoexcitation in comparison to collision induced dissociation (CID), six adrenocorticotropic hormone (ACTH) peptides in a range of charge states were subjected to 266 nm ultraviolet photodissociation (UVPD), 193 nm UVPD, and CID. Similar fragment ions and distributions were observed for 266 nm UVPD and 193 nm UVPD for all peptides investigated. While both UVPD and CID led to preferential cleavage of the Y-S bond for all ACTH peptides [except ACTH (1-39)], UVPD was far less dependent on charge state and location of basic sites for the production of C-terminal and N-terminal ions. For ACTH (1-16), ACTH (1-17), ACTH (1-24), and ACTH (1-39), changes in the distributions of fragment ion types ( a, b, c, x, y, z, and collectively N-terminal ions versus C-terminal ions) showed only minor changes upon UVPD for all charge states. In contrast, CID displayed significant changes in the fragment ion type distributions as a function of charge state, an outcome consistent with the dependence on the number and location of mobile protons that is not prominent for UVPD. Sequence coverages obtained by UVPD showed less dependence on charge state than those determined by CID, with the latter showing a consistent decrease in coverage as charge state increased.

  2. Peripheral nerve regeneration following transection injury to rat sciatic nerve by local application of adrenocorticotropic hormone.

    PubMed

    Mohammadi, Rahim; Yadegarazadi, Mohammad-Javad; Amini, Keyvan

    2014-09-01

    The objective of this study was to assess local effect of adrenocorticotropic hormone (ACTH) on the functional recovery of the sciatic nerve in a transection model. Sixty male healthy white Wistar rats were randomized into four experimental groups of 15 animals each: In the sham-operated group (SHAM), the sciatic nerve was exposed and manipulated. In the transected group (TC), the left sciatic nerve was transected and the cut nerve ends were fixed in the adjacent muscle. In the silicone graft group (SIL) a 10-mm defect was made and bridged using a silicone tube. The graft was filled with phosphated-buffer saline alone. In the treatment group a silicone tube (SIL/ACTH) was filled with 10 μL ACTH (0.1 mg/mL). Each group was subdivided into three subgroups of five animals each and regenerated nerve fibres were studied at 4, 8 and 12 weeks post operation. Behavioral testing, functional, gastrocnemius muscle mass and morphometric indices showed earlier regeneration of axons in SIL/ACTH than in SIL group (p < 0.05). Immunohistochemistry clearly showed more positive location of reactions to S-100 in SIL/ACTH than in SIL group. ACTH improved functional recovery and morphometric indices of sciatic nerve. This finding supports role of ACTH after peripheral nerve repair and may have clinical implications for the surgical management of patients after nerve transection.

  3. Pancreatic solitary fibrous tumor causing ectopic adrenocorticotropic hormone syndrome.

    PubMed

    Murakami, Keigo; Nakamura, Yasuhiro; Felizola, Saulo J A; Morimoto, Ryo; Satoh, Fumitoshi; Takanami, Kentaro; Katakami, Hideki; Hirota, Seiichi; Takeda, Yoshiyu; Meguro-Horike, Makiko; Horike, Shin-Ichi; Unno, Michiaki; Sasano, Hironobu

    2016-11-15

    Solitary fibrous tumors occasionally present with hypoglycemia because of the excessive release of insulin-like growth factor II. We report the first case of pancreatic solitary fibrous tumor causing ectopic adrenocorticotropic hormone syndrome. An 82-year-old Japanese man presented with lower limb edema, uncontrolled hypertension, hypokalemia, and baseline hypercortisolism. Distal pancreatectomy was performed after the clinical diagnosis of a neuroendocrine tumor with ectopic secretion of adrenocorticotropic hormone. On histological examination, the tumor showed spindle cells in a fascicular arrangement. The diagnosis of the solitary fibrous tumor was confirmed by the identification of the NAB2-STAT6 fusion gene and positive immuno-histochemical staining for STAT6 and CD34. Using quantitative real-time polymerase chain reaction, mRNA that encoded proopiomelanocortin, precursor of adrenocorticotropic hormone, was detected. Proopiomelanocortin production through the demethylation of the promoter region Domain IV was detected. Pancreatic solitary fibrous tumors represent a new cause of ectopic adrenocorticotropic hormone syndrome.

  4. Case of multiple endocrine neoplasia 2B with probable ectopic adrenocorticotropic hormone-secreting liver metastasis from medullary thyroid carcinoma.

    PubMed

    Kurozumi, Akira; Okada, Yosuke; Arao, Tadashi; Nakamoto, Yuji; Togashi, Kaori; Tanaka, Yoshiya

    2013-09-01

    A 31 year old woman was diagnosed with multiple endocrine neoplasia (MEN) 2B at 10 years old. Dark pigmentation gradually developed on her skin and her serum adrenocorticotropic hormone (ACTH) was high, suggesting concurrent ectopic ACTH syndrome (EAS). Corticotropin-releasing hormone (CRH) loading test ruled out Cushing's disease and supported the diagnosis of EAS. Multiple low attenuation mass in the liver was observed in a computed tomography (CT) scan, and was suspected as ectopic ACTH-secreting metastatic tumor from medullary thyroid carcinoma (MTC). ACTH production by MTC is relatively rare, particularly in patients with MEN; patients with ectopic ACTH-secreting liver metastatic tumor from MTC in MEN 2B have never been reported previously.

  5. Adrenocorticotropic hormone in serial cerebrospinal fluid in man - Subject to acute regulation by the hypothalamic-pituitary-adrenocortical system?

    PubMed

    Kellner, Michael; Wortmann, Viola; Salzwedel, Cornelie; Kober, Daniel; Petzoldt, Martin; Urbanowicz, Tatiana; Pulic, Mersija; Boelmans, Kai; Yassouridis, Alexander; Wiedemann, Klaus

    2016-05-30

    Acute regulation of adrenocorticotropic hormone (ACTH) in cerebrospinal fluid (CSF) by the hypothalamic-pituitary-adrenocortical system has not been investigated in man. In a pilot study in healthy male volunteers we measured ACTH every twenty minutes in serial CSF for three hours after an intravenous placebo, hydrocortisone (100mg) or insulin (2mg/kg) injection. No acute inhibitory or stimulatory effects of these interventions were discovered. Our results corroborate previous findings in rhesus monkeys. The regulation of CSF ACTH and its potential relevance for behavioral alterations in health and disease (e.g. major depression or anorexia nervosa) in humans need further study.

  6. The central anorexigenic mechanism of adrenocorticotropic hormone involves the caudal hypothalamus in chicks.

    PubMed

    Shipp, Steven L; Yi, Jiaqing; Dridi, Sami; Gilbert, Elizabeth R; Cline, Mark A

    2015-10-01

    Adrenocorticotropic hormone (ACTH), consisting of 39 amino acids, is most well-known for its involvement in an organism's response to stress. It also participates in satiety, as exogenous ACTH causes decreased food intake in rats. However, its anorexigenic mechanism is not well understood in any species and its effect on appetite is not reported in the avian class. Thus, the present study was designed to evaluate central ACTH's effect on food intake and to elucidate the mechanism mediating this response using broiler chicks. Chicks that received intracerebroventricular (ICV) injection of 1, 2, or 4 nmol of ACTH reduced food intake, under both ad libitum and 180 min fasted conditions. Water intake was also reduced in ACTH-injected chicks under both feeding conditions, but when measured without access to feed it was not affected. Blood glucose was not affected in either feeding condition. Following ACTH injection, c-Fos immunoreactivity was quantified in key appetite-associated hypothalamic nuclei including the ventromedial hypothalamus (VMH), dorsomedial hypothalamus, lateral hypothalamus (LH), arcuate nucleus (ARC) and the parvo- and magno-cellular portions of the paraventricular nucleus. ACTH-injected chicks had increased c-Fos immunoreactivity in the VMH, LH, and ARC. Hypothalamus was collected at 1h post-injection, and real-time PCR performed to measure mRNA abundance of some appetite-associated factors. Neuropeptide Y, pro-opiomelanocortin, glutamate decarboxylase 1, melanocortin receptors 2-5, and urocortin 3 mRNA abundance was not affected by ACTH treatment. However, expression of corticotropin releasing factor (CRF), urotensin 2 (UT), agouti-related peptide (AgRP), and orexin (ORX), and melanocortin receptor 1 (MC1R) mRNA decreased in the hypothalamus of ACTH-injected chicks. In conclusion, ICV ACTH causes decreased food intake in chicks, and is associated with VMH, LH, and ARC activation, and a decrease in hypothalamic mRNA abundance of CRF, UT, AgRP, ORX

  7. Isolated double adrenocorticotropic hormone-secreting pituitary adenomas: A case report and review of the literature

    PubMed Central

    PU, JIUJUN; WANG, ZHIMING; ZHOU, HUI; ZHONG, AILING; JIN, KAI; RUAN, LUNLIANG; YANG, GANG

    2016-01-01

    Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas. PMID:27347184

  8. Isolated double adrenocorticotropic hormone-secreting pituitary adenomas: A case report and review of the literature.

    PubMed

    Pu, Jiujun; Wang, Zhiming; Zhou, Hui; Zhong, Ailing; Jin, Kai; Ruan, Lunliang; Yang, Gang

    2016-07-01

    Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas.

  9. Adrenocorticotropic hormone analog use for podocytopathies

    PubMed Central

    Filippone, Edward J; Dopson, Shirley J; Rivers, Denise M; Monk, Rebeca D; Udani, Suneel M; Jafari, Golriz; Huang, Solomon C; Melhem, Arafat; Assioun, Bassim; Schmitz, Paul G

    2016-01-01

    Background Adrenocorticotropic hormone is being increasingly studied for treatment of various glomerulopathies, most notably membranous nephropathy. Less data are available regarding its use in idiopathic nephrotic syndrome (INS) secondary to minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). We report here our experience with H.P. Acthar® Gel (repository corticotropin injection) as first-line or subsequent therapy in patients with INS. Methods Data were taken from three patients with MCD and ten patients with FSGS from around the US, who were treated with Acthar Gel as initial or subsequent therapy. Treatment was solely at the discretion of the primary nephrologist without a specific protocol. A complete response (CR) was defined as final urine protein-to-creatinine ratio <500 mg/g and a partial response (PR) as 50% decrease without rise of serum creatinine. Side effects and tolerability were noted. Results All three patients with MCD received Acthar Gel as second-line or later immunosuppressive (IS) therapy and all responded (one CR and two PRs). Two of the ten patients with FSGS received Acthar Gel as first-line IS therapy, while the other eight had failed multiple agents. Four of the ten patients with FSGS had responses, including two CRs and two PRs. The three patients with MCD tolerated therapy well without side effects. Five patients with FSGS tolerated therapy well, while five had various steroid-like side effects, resulting in therapy discontinuation in two patients. Conclusion Acthar Gel is a viable alternative IS agent for treatment of INS in patients intolerant or resistant to conventional therapy. More data are needed to better define its appropriate place. PMID:27418857

  10. Differential expression of functional adrenocorticotropic hormone receptors by subpopulations of lymphocytes

    SciTech Connect

    Clarke, B.L.; Bost, K.L.

    1989-07-15

    In an effort to investigate the presence of adrenocorticotropic hormone (ACTH) receptors on rat lymphocytes, cells were separated by a panning procedure into T and B cell populations. By using the radiolabeled ACTH agonist, (/sup 125/I-Tyr23) phenylalanine2-norleucine4-ACTH1-24, substantial numbers of ACTH binding sites were detected on T and B lymphocytes, but not on thymocytes. Scatchard analysis revealed two types of binding sites on each cell population, one with Kd1 = 0.088 +/- 0.025 nM and one with Kd2 = 4.2 +/- 0.6 nM; however, the absolute number of binding sites per cell was different. B lymphocytes expressed approximately three times the number of Kd1 binding sites per cell when compared with T lymphocytes. However, ACTH receptor expression by these cell populations was not static as suggested by the ability to induce receptor expression via mitogens. B or T cells and thymocytes stimulated with the mitogens LPS or Con A, respectively, substantially increased their number of Kd1 binding sites per cell (approximately three-fold). Even more dramatic increases in Kd1 receptor expression (approximately 100-fold) were observed when comparing ''normal'' and stimulated thymocytes. To demonstrate that these ACTH binding sites were in fact functional, cAMP levels were measured in lymphocytes 10 min after exposure to varying concentrations of ACTH. Dose-dependent increases in cAMP levels were observed, with significant stimulation occurring with as little as 0.1 nM ACTH added. Taken together, these studies demonstrate the presence of functional ACTH receptors on normal, rat T and B lymphocytes.

  11. Quantifying Pituitary-Adrenal Dynamics and Deconvolution of Concurrent Cortisol and Adrenocorticotropic Hormone Data by Compressed Sensing

    PubMed Central

    Faghih, Rose T.; Dahleh, Munther A.; Adler, Gail K.; Klerman, Elizabeth B.; Brown, Emery N.

    2015-01-01

    Pulsatile release of cortisol from the adrenal glands is governed by pulsatile release of adrenocorticotropic hormone (ACTH) from the anterior pituitary. In return, cortisol has a negative feedback effect on ACTH release. Simultaneous recording of ACTH and cortisol is not typical, and determining the number, timing, and amplitudes of pulsatile events from simultaneously recorded data is challenging because of several factors: (I) stimulator ACTH pulse activity, (II) kinematics of ACTH and cortisol, (III) the sampling interval, and (IV) the measurement error. We model ACTH and cortisol secretion simultaneously using a linear differential equations model with Gaussian errors and sparse pulsatile events as inputs to the model. We propose a novel framework for recovering pulses and parameters underlying the interactions between ACTH and cortisol. We recover the timing and amplitudes of pulses using compressed sensing, and employ generalized cross validation for determining the number of pulses. We analyze serum ACTH and cortisol levels sampled at 10-minute intervals over 24 hours from 10 healthy women. We recover physiologically plausible timing and amplitudes for these pulses and model the feedback effect of cortisol. We recover 15 to 18 pulses over 24 hours, which is highly consistent with the results of another cortisol data analysis approach. Modeling the interactions between ACTH and cortisol allows for accurate quantification of pulsatile events, and normal and pathological states. This could lay the basis for a more physiologically-based approach for administering cortisol therapeutically. The proposed approach can be adapted to deconvolve other pairs of hormones with similar interactions. PMID:25935025

  12. Quantifying Pituitary-Adrenal Dynamics and Deconvolution of Concurrent Cortisol and Adrenocorticotropic Hormone Data by Compressed Sensing.

    PubMed

    Faghih, Rose T; Dahleh, Munther A; Adler, Gail K; Klerman, Elizabeth B; Brown, Emery N

    2015-10-01

    Pulsatile release of cortisol from the adrenal glands is governed by pulsatile release of adrenocorticotropic hormone (ACTH) from the anterior pituitary. In return, cortisol has a negative feedback effect on ACTH release. Simultaneous recording of ACTH and cortisol is not typical, and determining the number, timing, and amplitudes of pulsatile events from simultaneously recorded data is challenging because of several factors: 1) stimulator ACTH pulse activity, 2) kinematics of ACTH and cortisol, 3) the sampling interval, and 4) the measurement error. We model ACTH and cortisol secretion simultaneously using a linear differential equations model with Gaussian errors and sparse pulsatile events as inputs to the model. We propose a novel framework for recovering pulses and parameters underlying the interactions between ACTH and cortisol. We recover the timing and amplitudes of pulses using compressed sensing and employ generalized cross validation for determining the number of pulses. We analyze serum ACTH and cortisol levels sampled at 10-min intervals over 24 h from ten healthy women. We recover physiologically plausible timing and amplitudes for these pulses and model the feedback effect of cortisol. We recover 15 to 18 pulses over 24 h, which is highly consistent with the results of another cortisol data analysis approach. Modeling the interactions between ACTH and cortisol allows for accurate quantification of pulsatile events, and normal and pathological states. This could lay the basis for a more physiologically-based approach for administering cortisol therapeutically. The proposed approach can be adapted to deconvolve other pairs of hormones with similar interactions.

  13. Improved response of growth hormone to growth hormone-releasing hormone and reversible chronic thyroiditis after hydrocortisone replacement in isolated adrenocorticotropic hormone deficiency.

    PubMed

    Inagaki, Miho; Sato, Haruhiro; Miyamoto, Yoshiyasu; Hirukawa, Takashi; Sawaya, Asako; Miyakogawa, Takayo; Tatsumi, Ryoko; Kakuta, Takatoshi

    2009-07-20

    We report a 44-year-old Japanese man who showed a reversible blunted response of growth hormone (GH) to GH-releasing hormone (GRH) stimulation test and reversible chronic thyroiditis accompanied by isolated ACTH deficiency. He was admitted to our hospital because of severe general malaise, hypotension, and hypoglycemia. He showed repeated attacks of hypoglycemia, and his serum sodium level gradually decreased. Finally, he was referred to the endocrinology division, where his adrenocorticotropic hormone (ACTH) and cortisol values were found to be low, and his GH level was slightly elevated. An increased value of thyroid stimulating hormone (TSH) and decreased values of free triidothyronine and free thyroxine were observed along with anti-thyroglobulin antibody, suggesting chronic thyroiditis. Pituitary stimulation tests revealed a blunted response of ACTH and cortisol to corticotropin-releasing hormone, and a blunted response of GH to GRH. Hydrocortisone replacement was then started, and this improved the patient's general condition. His hypothyroid state gradually ameliorated and his titer of anti-thyroglobulin antibody decreased to the normal range. Pituitary function was re-evaluated with GRH stimulation test under a maintenance dose of 20 mg/day hydrocortisone and showed a normal response of GH to GRH. It is suggested that re-evaluation of pituitary and thyroid function is useful for diagnosing isolated ACTH deficiency after starting a maintenance dose of hydrocortisone in order to avoid unnecessary replacement of thyroid hormone.

  14. Depressive-like behavior in adrenocorticotropic hormone-treated rats blocked by memantine.

    PubMed

    Tokita, Kenichi; Fujita, Yuko; Yamaji, Takayuki; Hashimoto, Kenji

    2012-08-01

    Hyperactivity of the hypothalamic pituitary-adrenal (HPA) axis plays a role in the pathophysiology of major depressive disorder (MDD). Recent studies suggest the role of the glutamatergic system in the pathophysiology of MDD, and N-methyl-D-aspartate (NMDA) receptor antagonists have shown antidepressant effects in both preclinical and clinical studies. However, little is known about the role of adrenocorticotropic hormone (ACTH) specifically in the glutamatergic response to HPA axis activation. Glutamate is an NMDA receptor agonist, and glycine and D-serine act as co-agonists. Here, we measured brain concentrations of these amino acids in rats given repeated administration of ACTH (100 μg/rat/day, sc, for 14 days). Further, we also evaluated behavioral effects of memantine, a non-competitive NMDA antagonist, on immobility time in the forced swimming test and on locomotor activity in ACTH-treated rats. Compared with control rats, glutamine, glycine, L-serine, and D-serine levels were increased in the hippocampus of ACTH-treated rats; glutamate, glutamine, glycine, L-serine, and D-serine were increased in the cerebellum; and glutamine and glycine were increased in the frontal cortex and striatum, all with statistical significance. Remarkably, these increases in agonists and co-agonists might have led to the augmentation of NMDA receptor activity. ACTH treatment increased immobility time in the forced swimming test and decreased locomotor activity in rats. On the contrary, memantine (10 mg/kg, ip) significantly decreased immobility time in the forced swimming test and increased locomotor activity in ACTH-treated rats. Furthermore, imipramine (15 mg/kg, ip) did not alter immobility time in the forced swimming test whereas this drug significantly decreased locomotor activity in ACTH-treated rats. These results suggest that depressive-like behaviors by chronic ACTH treatment could be blocked by memantine.

  15. Surgical treatment of ectopic adrenocorticotropic hormone syndrome with intra-thoracic tumor

    PubMed Central

    Zhou, Xiang; Hang, Junbiao; Che, Jiaming; Chen, Zhongyuan; Qiu, Weicheng; Ren, Jian; Yang, Xiaoqing; Xiang, Jie

    2016-01-01

    Background The study was to review the clinical manifestations and laboratory examinations of ectopic adrenocorticotropic hormone (ACTH) syndrome, and to analyze the efficacy of surgical treatment. Methods The clinical data, surgical therapy, and outcome of 23 cases of ectopic ACTH syndrome accompanied by intra-thoracic tumors were reviewed. The tumors were removed from all the patients according to the principles of radical resection. Results The tumors were confirmed as associated with ectopic ACTH secretion in 19 cases. Hyperglycemia and hypokalemia were recovered, while plasma cortisol, plasma ACTH and 24-hour urinary free cortisol (UFC) levels were significantly reduced after surgery in these 19 cases. Recurrences of the disease were found in six cases during following-up, and five of them died. Conclusions The thoracic cavity should be a focus in routine examinations of patients with symptoms of Cushing’s syndrome (CS), because ectopic ACTH-producing tumors are commonly found in bronchus/lung and mediastinum. Despite the incidence of the pulmonary nodule secondary to opportunistic infection in some cases, surgery is still the first choice if the tumor is localized. The surgical procedure should be performed according to the principles in resection of lung cancer and mediastinal tumor. The surgical efficacy is significant for short-term periods; however, the recurrence of the disease in long-term periods is in great part related to distal metastasis or relapse of the tumor. PMID:27162663

  16. [A Case of an Adrenocorticotropic Hormone-Producing Pituitary Adenoma Removed via Electromagnetic-Guided Neuroendoscopy].

    PubMed

    Tomita, Yusuke; Kurozumi, Kazuhiko; Terasaka, Tomohiro; Inagaki, Kenichi; Otsuka, Fumio; Date, Isao

    2016-06-01

    The use of navigation systems is safe and reliable for neurological surgery. We performed endoscopic transsphenoidal surgery to totally resect an adrenocorticotropic hormone (ACTH)-producing pituitary adenoma associated with oculomotor nerve palsy. A 70-year-old woman developed right ptosis 4 months before admission. She developed anisocoria 2 months later and was referred to the department of neurology from clinic. Brain magnetic resonance imaging(MRI)showed an intrasellar tumor that partially invaded the right cavernous sinus, and she was then referred to our department. She exhibited a round face ("moon face") and central obesity. Laboratory test results showed a high urinary cortisol level and high serum ACTH level, and neither the serum cortisol nor ACTH level was suppressed by a low-dose dexamethasone test. We performed transsphenoidal surgery using high-dimensional endoscopy under electromagnetic navigation. The tumor invading the cavernous sinus was visualized via endoscopy and confirmed on navigation using a flexible needle probe. Postoperative MRI showed total removal of the tumor, and the serum ACTH level recovered to the normal range. The patient's right oculomotor palsy resolved within 1 week postoperatively. In summary, electromagnetic navigation was useful for total resection of a pituitary tumor invading the cavernous sinus, contributing to normalization of the ACTH level and improvement in neurological symptoms.

  17. Adrenocorticotropic hormone, melanocyte-stimulating hormone, and the melanocortin receptors: revisiting the work of Robert Schwyzer: a thirty-year retrospective.

    PubMed

    Dores, Robert M

    2009-04-01

    In 1977 Dr. Robert Schwyzer wrote the review ACTH: A Short Introductory Review, which provided a reference point for current structure/function studies on the interactions between adrenocorticotropic hormone and alpha-melanocyte-stimulating hormone and the melanocortin receptors. This mini review will evaluate how the predictions made in the 1977 review have held up and also propose a mechanism to explain the ligand selectivity properties of the melanocortin receptors.

  18. Effects of ghrelin, growth hormone-releasing peptide-6, and growth hormone-releasing hormone on growth hormone, adrenocorticotropic hormone, and cortisol release in type 1 diabetes mellitus.

    PubMed

    de Sá, Larissa Bianca Paiva Cunha; Nascif, Sergio Oliva; Correa-Silva, Silvia Regina; Molica, Patricia; Vieira, José Gilberto Henriques; Dib, Sergio Atala; Lengyel, Ana-Maria Judith

    2010-10-01

    In type 1 diabetes mellitus (T1DM), growth hormone (GH) responses to provocative stimuli are normal or exaggerated, whereas the hypothalamic-pituitary-adrenal axis has been less studied. Ghrelin is a GH secretagogue that also increases adrenocorticotropic hormone (ACTH) and cortisol levels, similarly to GH-releasing peptide-6 (GHRP-6). Ghrelin's effects in patients with T1DM have not been evaluated. We therefore studied GH, ACTH, and cortisol responses to ghrelin and GHRP-6 in 9 patients with T1DM and 9 control subjects. The GH-releasing hormone (GHRH)-induced GH release was also evaluated. Mean fasting GH levels (micrograms per liter) were higher in T1DM (3.5 ± 1.2) than in controls (0.6 ± 0.3). In both groups, ghrelin-induced GH release was higher than that after GHRP-6 and GHRH. When analyzing Δ area under the curve (ΔAUC) GH values after ghrelin, GHRP-6, and GHRH, no significant differences were observed in T1DM compared with controls. There was a trend (P = .055) to higher mean basal cortisol values (micrograms per deciliter) in T1DM (11.7 ± 1.5) compared with controls (8.2 ± 0.8). No significant differences were seen in ΔAUC cortisol values in both groups after ghrelin and GHRP-6. Mean fasting ACTH values were similar in T1DM and controls. No differences were seen in ΔAUC ACTH levels in both groups after ghrelin and GHRP-6. In summary, patients with T1DM have normal GH responsiveness to ghrelin, GHRP-6, and GHRH. The ACTH and cortisol release after ghrelin and GHRP-6 is also similar to controls. Our results suggest that chronic hyperglycemia of T1DM does not interfere with GH-, ACTH-, and cortisol-releasing mechanisms stimulated by these peptides.

  19. Effects of different fixatives on demonstrating epinephrine and ACTH hormones in Tetrahymena.

    PubMed

    Csaba, G; Kovács, P; Pállinger, E

    2009-12-01

    The unicellular Tetrahymena produces, contains, and secretes many hormones characteristic of higher animals. We tested three fixatives, formaldehyde, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC), and glutaraldehyde for suitability for immunocytochemical demonstration of epinephrine and adrenocorticotropic harmone (ACTH) in Tetrahymena. Using flow cytometric immunocytochemistry, staining of ACTH was highest after EDAC fixation and that of epinephrine after glutaraldehyde fixation. Using laser scanning confocal microscopy, formaldehyde fixation prevented staining. Glutaraldehyde fixation produced high autofluorescence, which obscured specific staining. After EDAC fixation, ACTH was localized in the ciliary row; however, demonstration of epinephrine was not improved. Our results show that there is no "fixative for any hormone." Different fixatives are needed to demonstrate different hormones in Tetrahymena.

  20. Effects of adrenocorticotropic hormone challenge and age on hair cortisol concentrations in dairy cattle

    PubMed Central

    del Rosario González-de-la-Vara, Marcela; Valdez, Ricardo Arturo; Lemus-Ramirez, Vicente; Vázquez-Chagoyán, Juan Carlos; Villa-Godoy, Alejandro; Romano, Marta C.

    2011-01-01

    Dairy cattle suffer stress from management and production; contemporary farming tries to improve animal welfare and reduce stress. Therefore, the assessment of long-term hypothalamic-pituitary-adrenal function using non-invasive techniques is useful. The aims in this study were: to measure cortisol concentration in cow and calves hair by radioimmunoassay (RIA), to test cortisol accumulation in bovine hair after adrenocorticotropic hormone (ACTH) challenges, and determine the influence of hair color on cortisol concentrations. Fifteen Holstein heifers were allotted to 3 groups (n = 5 each): in control group (C), just the hair was sampled; in the saline solution group (SS), IV saline solution was administered on days 0, 7, and 14; and the ACTH group was challenged 3 times with ACTH (0.15 UI per kg of body weight) on days 0, 7, and 14. Serum samples from the SS and ACTH groups were obtained 0, 60 and 90 min post-injection. Serum cortisol concentration was greater 60 and 90 min after injection with ACTH. Hair was clipped on days 0, 14, 28, and 44. Hair cortisol was methanol extracted and measured by RIA. Hair cortisol was preserved for 11 mo. Hair cortisol concentrations in the ACTH group were greater than in the saline and control groups on days 14 and 28, but not on day 44. Concentrations were greater in calves than in cows and greater in white hair than in black hair. Cortisol accumulated in bovine hair after ACTH challenges, but the concentration was affected by both age and hair color. If hair color effects are taken into account, assessing cortisol concentration in hair is a potentially useful non-invasive method for assessing stress in cattle. PMID:22210998

  1. Effects of adrenocorticotropic hormone challenge and age on hair cortisol concentrations in dairy cattle.

    PubMed

    González-de-la-Vara, Marcela del Rosario; Valdez, Ricardo Arturo; Lemus-Ramirez, Vicente; Vázquez-Chagoyán, Juan Carlos; Villa-Godoy, Alejandro; Romano, Marta C

    2011-07-01

    Dairy cattle suffer stress from management and production; contemporary farming tries to improve animal welfare and reduce stress. Therefore, the assessment of long-term hypothalamic-pituitary-adrenal function using non-invasive techniques is useful. The aims in this study were: to measure cortisol concentration in cow and calves hair by radioimmunoassay (RIA), to test cortisol accumulation in bovine hair after adrenocorticotropic hormone (ACTH) challenges, and determine the influence of hair color on cortisol concentrations. Fifteen Holstein heifers were allotted to 3 groups (n = 5 each): in control group (C), just the hair was sampled; in the saline solution group (SS), IV saline solution was administered on days 0, 7, and 14; and the ACTH group was challenged 3 times with ACTH (0.15 UI per kg of body weight) on days 0, 7, and 14. Serum samples from the SS and ACTH groups were obtained 0, 60 and 90 min post-injection. Serum cortisol concentration was greater 60 and 90 min after injection with ACTH. Hair was clipped on days 0, 14, 28, and 44. Hair cortisol was methanol extracted and measured by RIA. Hair cortisol was preserved for 11 mo. Hair cortisol concentrations in the ACTH group were greater than in the saline and control groups on days 14 and 28, but not on day 44. Concentrations were greater in calves than in cows and greater in white hair than in black hair. Cortisol accumulated in bovine hair after ACTH challenges, but the concentration was affected by both age and hair color. If hair color effects are taken into account, assessing cortisol concentration in hair is a potentially useful non-invasive method for assessing stress in cattle.

  2. Mapping of enkephalins and adrenocorticotropic hormone in the squirrel monkey brainstem.

    PubMed

    Duque-Díaz, Ewing; Díaz-Cabiale, Zaida; Narváez, José Angel; Coveñas, Rafael

    2017-03-01

    An immunocytochemical technique has been used to study for the first time the distribution of fibers and cell bodies containing leucine-enkephalin (leu-enk), methionine-enkephalin (met-enk) or adrenocorticotropic hormone (ACTH) in the whole brainstem of the squirrel monkey Saimiri sciureus. Cell bodies containing leu-enk or met-enk were found in the superior colliculus and the formatio reticularis tegmenti mesencephali, respectively. No immunoreactive cell bodies containing ACTH were observed. Leu-enk-immunoreactive fibers were observed in 40 brainstem nuclei/tracts/regions, fibers containing met-enk were found in 38 brainstem nuclei/tracts/regions and fibers containing ACTH were found in 26 nuclei/tracts/regions. In the latter case, the density of immunoreactive fibers was always low. A high/moderate density of leu-enk- or met-enk-immunoreactive fibers were found in 18 and 16 brainstem nuclei/tracts/regions, respectively. The distribution of immunoreactive fibers containing leu-enk or met-enk was quite similar, with both leu-enk and met-enk observed in 82.5 % of the squirrel monkey brainstem nuclei/tracts/regions. This relationship is less marked for met-enk and ACTH (60.5 %) and even lower for leu-enk and ACTH (52.5 %). In 42.5 % of the nuclei/tracts/regions of the squirrel monkey brainstem (colliculus superior, substantia grisea centralis, nucleus interpeduncularis, nucleus tractus spinalis nervi trigemini, nucleus tractus solitarii, nucleus parabrachialis, formatio reticularis, substantia nigra), we observed fibers containing all three neuropeptides. The widespread distribution reported here suggests that enkephalins and ACTH can be involved in several physiological functions. The distribution of the immunoreactive fibers reported here is quite similar to that previously reported for enkephalins and ACTH in Macaca species and humans.

  3. Ectopic adrenocorticotropic hormone syndrome caused by neuroendocrine carcinoma of the colon.

    PubMed

    Fujimoto, Kazuyo; Nakashima, Takatoshi; Sasaki, Kazunari; Hayashi, Kenichi; Hanafusa, Masao; Yoshida, Shiei; Myojo, Satoshi; Yoshida, Shun-Ichi; Sawai, Shigeaki; Sano, Nobuya

    A 48-year-old woman with a history of autoimmune hemolytic anemia and taking long-term corticosteroid therapy presented with a 3-month history of general fatigue, abdominal distension, and pigmentation. A computed tomography scan of the abdomen showed a tumor in the sigmoid colon and multiple metastatic nodules in the liver. A colonoscopy revealed an obstructing mass with the presence of an irregular ulcer in the sigmoid colon. Following biopsy and histopathological analysis, the patient was diagnosed with neuroendocrine carcinoma (NEC) of the colon. She received her first cycle of chemotherapy, with carboplatin and etoposide. During hospitalization, her pigmentation and hypertension worsened and hypokalemia was observed, all of which suggsted Cushing's syndrome. Her plasma adrenocorticotropic hormone (ACTH) and cortisol levels were high, and an ectopic ACTH-producing tumor was suspected. After a second chemotherapy cycle, she developed neutropenic fever and subsequently died. At autopsy, two histological types were found in the tumor: small cell carcinoma and large cell NEC. Immunohistochemical analysis revealed ACTH in the large cell NEC. This is the first reported case of an ectopic ACTH syndrome caused by NEC of the colon.

  4. Isolated Adrenocorticotropic Hormone or Thyrotropin Deficiency Following Mild Traumatic Brain Injury: Three Cases with Long-Term Follow-Up

    PubMed Central

    Baek, Cho-Ok; Kim, Yu Ji; Kim, Ji Hye

    2015-01-01

    Few studies have examined the clinical features and long-term outcomes of isolated pituitary hormone deficiencies after traumatic brain injury (TBI). Such deficiencies typically present at time intervals after TBI, especially after mild injuries such as concussions, which makes their diagnosis difficult without careful history taking. It is necessary to improve diagnosis and prevent life threatening or morbid conditions such as those that may occur in deficiencies of adrenocorticotropic hormone (ACTH) or thyroid-stimulating hormone (as known as thyrotropin, TSH), the two most important pituitary hormones in hypopituitarism treatment. Here, we report two cases of isolated ACTH deficiency and one case of isolated TSH deficiency. These patients presented at different time points after concussion and underwent long-term follow-ups. PMID:27169080

  5. Isolated Adrenocorticotropic Hormone or Thyrotropin Deficiency Following Mild Traumatic Brain Injury: Three Cases with Long-Term Follow-Up.

    PubMed

    Baek, Cho-Ok; Kim, Yu Ji; Kim, Ji Hye; Park, Ji Hyun

    2015-10-01

    Few studies have examined the clinical features and long-term outcomes of isolated pituitary hormone deficiencies after traumatic brain injury (TBI). Such deficiencies typically present at time intervals after TBI, especially after mild injuries such as concussions, which makes their diagnosis difficult without careful history taking. It is necessary to improve diagnosis and prevent life threatening or morbid conditions such as those that may occur in deficiencies of adrenocorticotropic hormone (ACTH) or thyroid-stimulating hormone (as known as thyrotropin, TSH), the two most important pituitary hormones in hypopituitarism treatment. Here, we report two cases of isolated ACTH deficiency and one case of isolated TSH deficiency. These patients presented at different time points after concussion and underwent long-term follow-ups.

  6. Laparoscopic Unilateral Total and Contralateral Subtotal Adrenalectomy for Bilateral Adrenocorticotropic Hormone-Secreting Pheochromocytoma: Report of a Rare Case

    PubMed Central

    Fukasawa, Masanari; Miyamoto, Tatsuya; Kira, Satoru; Aoki, Tadashi; Zakoji, Hidenori; Mitsui, Takahiko; Takeda, Masayuki

    2016-01-01

    Abstract Background: Bilateral adrenal tumors are not common in clinical practice, but are an important source of ectopic adrenocorticotropic hormone (ACTH) secretion. Standard operative management for bilateral pheochromocytomas might dictate the removal of the involved adrenal gland and the removal of the contralateral adrenal gland. We present a case of bilateral ACTH-secreting pheochromocytoma treated with staged laparoscopic unilateral total and contralateral subtotal adrenalectomy. Case Presentation: A 58-year-old male with elevated hyperglycemia and general fatigue was hospitalized for pneumonia. CT incidentally revealed bilateral adrenal tumor. Biochemical examination was significant for elevated urinary metanephrine and normetanephrines, and plasma catecholamine level. CT scan of the head, neck, thorax, and pelvis was normal. Under the clinical diagnosis of ACTH-dependent pheochromocytoma, laparoscopic right total adrenalectomy was performed. As endocrinologic examination showed residual ACTH-dependent pheochromocytoma after surgery, laparoscopic left subtotal adrenalectomy was performed. Pathology analysis revealed pheochromocytoma with stained ACTH lesions in both adrenal tumors. Conclusion: This is a rare case of ACTH-secreting bilateral pheochromocytoma effectively treated with staged laparoscopic unilateral total and contralateral subtotal adrenalectomy, in which the production of ACTH was confirmed by immunohistochemical staining. PMID:28078325

  7. Primary intracranial neuroendocrine tumor with ectopic adrenocorticotropic hormone syndrome: A rare and complicated case report and literature review

    PubMed Central

    LIU, HAILONG; ZHANG, MINGSHAN; WANG, XUAN; QU, YANMING; ZHANG, HONGWEI; YU, CHUNJIANG

    2016-01-01

    Neuroendocrine tumors (NETs) and ectopic adrenocorticotropic hormone (ACTH) syndrome are frequent in adult patients. However, primary intracranial NETs, exhibiting immunonegativity for ACTH, high serum ACTH level and treated with anterior skull base reconstruction, are rare and complicated. We herein present a case of a primary intracranial NET immunonegative for ACTH, resulting in ectopic ACTH syndrome. A 40-year-old woman presented with intermittent rhinorrhea, rapid weight gain, polydipsia, polyuria, hypertension, dimness, bilateral exophthalmus, diminution of vision in the left eye and pigmentation of the skin of the face and trunk. Computed tomography (CT) and magnetic resonance imaging scans revealed a sizeable enhancing tumor in the anterior cranial fossa, which infiltrated the sphenoid and ethmoid sinuses bilaterally, the left maxillary sinus and the nasal cavity. Abdominal CT scans revealed bilateral adrenal hyperplasia. The biochemical findings included hypokalemia and high glucose, cortisol, plasma ACTH, 24-h urinary free cortisol and testosterone levels. The neoplasm was exposed through a right frontal craniotomy, while anterior skull base reconstruction was performed during surgery. The intracranial surgery achieved gross removal of the tumor; however, part of the tumor remained in the nasal cavity. Histopathological examination of the surgical specimen confirmed the diagnosis of a low-grade small-cell NET, exhibiting immunonegativity for ACTH. A postoperative abdominal CT scan demonstrated bilateral regression of the adrenal gland hyperplasia and the serum ACTH level returned to normal after 16 days. To the best of our knowledge, there are no previous reports of primary intracranial NETs, immunohistochemically negative for ACTH, resulting in ectopic ACTH syndrome. PMID:27330775

  8. Linkage of congenital isolated adrenocorticotropic hormone deficiency to the corticotropin releasing hormone locus using simple sequence repeat polymorphisms

    SciTech Connect

    Kyllo, J.H.; Collins, M.M.; Vetter, K.L.

    1996-03-29

    Genetic screening techniques using simple sequence repeat polymorphisms were applied to investigate the molecular nature of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare cause of hypocortisolism shared by a brother and sister with two unaffected sibs and unaffected parents is inherited as an autosomal recessive single gene mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol sufficiency were investigated for a causal role in this disorder. Southern blotting showed no detectable mutations of the gene encoding pro-opiomelanocortin (POMC), the ACTH precursor. Other candidate genes subsequently considered were those encoding neuroendocrine convertase-1, and neuroendocrine convertase-2 (NEC-1, NEC-2), and corticotropin releasing hormone (CRH). Tests for linkage were performed using polymorphic di- and tetranucleotide simple sequence repeat markers flanking the reported map locations for POMC, NEC-1, NEC-2, and CRH. The chromosomal haplotypes determined by the markers flanking the loci for POMC, NEC-1, and NEC-2 were not compatible with linkage. However, 22 individual markers defining the chromosomal haplotypes flanking CRH were compatible with linkage of the disorder to the immediate area of this gene of chromosome 8. Based on these data, we hypothesize that the ACTH deficiency in this family is due to an abnormality of CRH gene structure or expression. These results illustrate the useful application of high density genetic maps constructed with simple sequence repeat markers for inclusion/exclusion studies of candidate genes in even very small nuclear families segregating for unusual phenotypes. 25 refs., 5 figs., 2 tabs.

  9. Inhibitory effects of trichostatin A on adrenocorticotropic hormone production and proliferation of corticotroph tumor AtT-20 cells.

    PubMed

    Nakada, Yuki; Kageyama, Kazunori; Sugiyama, Aya; Desaki, Rie; Takayasu, Shinobu; Niioka, Kanako; Murasawa, Shingo; Ishigame, Noriko; Asari, Yuko; Iwasaki, Yasumasa; Daimon, Makoto

    2015-01-01

    Cushing's disease is primarily caused by adrenocorticotropic hormone (ACTH)-producing pituitary adenomas. Pituitary tumor-transforming gene 1 (PTTG1) expression, a hallmark of pituitary tumors, stimulates pituitary cell proliferation. Histone deacetylases (HDACs) play an important role in regulating gene transcription and HDAC inhibitors induce cellular differentiation and suppress tumor cell proliferation. HDAC inhibitors also repress PTTG1 mRNA levels. Trichostatin A (TSA) is a potent cell-permeable HDAC inhibitor that blocks cell cycle progression. In the present study, we determined the effect of TSA on ACTH production and cellular proliferation in mouse AtT-20 corticotroph tumor cells. TSA decreased proopiomelanocortin (POMC) mRNA levels in AtT-20 cells and reduced ACTH levels in the culture medium of these cells. The TSA-induced decreases in POMC mRNA levels were not modulated when TSA and dexamethasone were simultaneously administered. Drug treatment also decreased AtT-20 cell proliferation, induced apoptosis, and increased the percentage of cells in G0/G1 phase using flow cytometry. TSA decreased PTTG1 mRNA levels. Furthermore, PTTG1 knockdown inhibited cellular proliferation. Its knockdown also inhibited POMC mRNA and ACTH levels. TSA inhibits ACTH production and corticotroph tumor cell proliferation. TSA may inhibit cellular proliferation, and ACTH synthesis and secretion by decreasing PTTG1 expression.

  10. NFKB2 mutation in common variable immunodeficiency and isolated adrenocorticotropic hormone deficiency

    PubMed Central

    Shi, Chuan; Wang, Fen; Tong, Anli; Zhang, Xiao-Qian; Song, Hong-Mei; Liu, Zheng-Yin; Lyu, Wei; Liu, Yue-Hua; Xia, Wei-Bo

    2016-01-01

    Abstract Background Common variable immunodeficiency (CVID) with central adrenal insufficiency is a recently defined clinical syndrome caused by mutations in the nuclear factor kappa-B subunit 2 (NFKB2) gene. We present the first case of NFKB2 mutation in Asian population. Methods and Results An 18-year-old Chinese female with adrenocorticotropic hormone (ACTH) deficiency was admitted due to adrenal crisis and pneumonia. She had a history of recurrent respiratory infections since childhood and ectodermal abnormalities were noted during physical examination. Immunologic tests revealed panhypogammaglobulinemia and deficient natural killer (NK)-cell function. DNA sequencing of NFKB2 identified a heterozygous nonsense mutation (c.2563 A>T, p.855: Lys>∗) in the patient but not her parents. Conclusion Clinicians should be alert to comorbidities of adrenal insufficiency and ectodermal dysplasia in CVID patients as these might suggest a rare hereditary syndrome caused by NFKB2 mutation. PMID:27749582

  11. Changes in plasma adrenocorticotropic hormone and cortisol levels induced by intracerebroventricular injection of histamine and its related compounds in dogs.

    PubMed

    Tsujimoto, S; Kamei, C; Yoshida, T; Tasaka, K

    1993-08-01

    Changes in plasma adrenocorticotropic hormone (ACTH) and cortisol levels induced by intracerebroventricular injection of histamine (H(i)) were studied in dogs. Intracerebroventricular administration of Hi at doses of 5 and 10 micrograms/kg caused a significant increase in plasma ACTH, while more rapid and more marked increase in plasma cortisol was noticed after Hi injection at doses of 2-10 micrograms/kg. Similar results were obtained when 2-methylhistamine was injected; remarkable increases in both plasma ACTH and cortisol levels were observed at doses of 25 and 50 micrograms/kg. However, no such effect was elicited by 4-methylhistamine even at a dose of 50 micrograms/kg. The rate of plasma cortisol increase induced by either Hi or 2-methylhistamine was significantly faster than that of plasma ACTH. Simultaneous application of pyrilamine (intracerebroventricularly) with H(i) resulted in the significant inhibition of H(i)-induced hormone secretions, but in similar administration neither ACTH nor cortisol were affected by cimetidine. In hypophysectomized dogs, a significant increase in plasma cortisol level was also observed after H(i) injection at a dose of 5 micrograms/kg. Intravenous infusion of hexamethonium continued before and after H(i) injection failed to inhibit the increase in plasma ACTH and cortisol levels induced by H(i). From these findings, it can be concluded that intracerebroventricular injection of H(i) caused an increase in plasma ACTH and cortisol levels via H1-receptor, and it is suggested that to some extent, the cortisol release elicited by H(i) is certainly produced without participation of ACTH.

  12. Inhibitory effects of SOM230 on adrenocorticotropic hormone production and corticotroph tumor cell proliferation in vitro and in vivo.

    PubMed

    Murasawa, Shingo; Kageyama, Kazunori; Sugiyama, Aya; Ishigame, Noriko; Niioka, Kanako; Suda, Toshihiro; Daimon, Makoto

    2014-08-25

    Adrenocorticotropic hormone (ACTH) production by pituitary corticotroph adenomas is the main cause of Cushing's disease. A drug that targets pituitary ACTH-secreting adenomas would aid treatment of Cushing's disease. Octreotide, a somatostatin receptor type 2 (SSTR2)-preferring somatostatin analogue, has no effect on ACTH secretion in patients with Cushing's disease. The multiligand SOM230 (pasireotide) displays a much higher affinity for SSTR1 and SSTR5 than octreotide and suppresses ACTH secretion in cultures of human corticotroph tumors to a greater extent than octreotide. In the present in vitro and in vivo study, we determined the effect of SOM230 on ACTH production and cell proliferation of AtT-20 corticotroph tumor cells. SOM230 decreased proopiomelanocortin (POMC) mRNA levels in AtT-20 cells and ACTH levels in the culture medium of these cells, suggesting that SOM230 suppresses ACTH synthesis and secretion in corticotroph tumor cells. SOM230 also decreased cell proliferation and both cyclic adenosine monophosphate response element-binding protein and Akt phosphorylation in AtT-20 cells. SSTR5 knockdown inhibited the SOM230-induced decreases in cell proliferation. Fluorescence-activated cell sorting analyses revealed that SOM230 did not attenuate cell cycle progression. Tumor weight in mice xenografted with AtT-20 cells and treated with SOM230 was significantly lower than in AtT-20-xenografted control mice. SOM230 also significantly decreased plasma ACTH levels, and POMC and pituitary tumor transforming gene mRNA levels in the tumor cells. Thus, SOM230 inhibits ACTH production and corticotroph tumor cell proliferation in vitro and in vivo.

  13. Adrenocorticotropic hormone therapy for the treatment of idiopathic nephrotic syndrome in children and young adults: a systematic review of early clinical studies with contemporary relevance.

    PubMed

    Lieberman, Kenneth V; Pavlova-Wolf, Anna

    2017-02-01

    Adrenocorticotropic hormone (ACTH) as a treatment for proteinuria due to nephrotic syndrome (NS) has re-emerged over the last decade. Current clinical data are primarily limited to adults with treatment-resistant NS. Largely unknown to today's clinicians is the existence of early clinical studies, following ACTH's introduction in the late 1940s, showing sustained proteinuria response in idiopathic NS in predominantly pediatric, treatment-naïve patients. Before ACTH, patients suffered severe edema and high mortality rates with no reliable or safe treatment. ACTH dramatically altered NS management, initially through recognition of diuresis effects and then through sustained proteinuria remission. This review synthesizes early clinical literature to inform current NS patient management. We undertook a MEDLINE search using MeSH terms "adrenocorticotropic hormone" and "nephrotic syndrome," with limits 1945-1965 and English. Sixty papers totaling 1137 patients were found; 14 studies (9 short-term, five long-term, N = 419 patients) met inclusion criteria. Studies were divided into two groups: short-term (≤28 days) and long-term (>5 weeks; short-term initial daily treatment followed by long-term intermittent)ACTH therapy and results were aggregated. An initial response, defined as a diuresis, occurred in 74 % of patients/treatment courses across nine short-term ACTH studies. Analyzed in eight of these studies, proteinuria response occurred in 56 % of patients/treatment courses. Across five long-term ACTH studies, proteinuria response was shown in 71 % of patients and was sustained up to 4.7 years following treatment. The inventory and re-evaluation of early clinical data broadens the evidence base of clinical experiences with ACTH for implementation of current treatment strategies and aiding the design of future studies.

  14. Effect of price increase of adrenocorticotropic hormone on treatment practices of infantile spasms.

    PubMed

    Wray, Carter D; Benke, Timothy A

    2010-09-01

    Intramuscular adrenocorticotropic hormone putatively constitutes the most efficacious treatment for infantile spasms. Adrenocorticotropic hormone in the United States is an "orphan drug," made by a single manufacturer. The price of adrenocorticotropic hormone increased almost 14-fold on August 27, 2007. We sought to evaluate the impact of this price increase on treatment practices at our institution, using a retrospective chart review of all children with infantile spasms treated during 2007-2009. We identified 97 patients whose spasms were treated using antiepileptic drugs, and we determined the length of stay for those hospitalized to initiate adrenocorticotropic hormone. Patients before the price increase were more likely to have been treated with adrenocorticotropic hormone as first medication, and were hospitalized 2.2 +/- 0.5 S.D. days for initiation. Patients after the price increase were more likely to have been treated initially with oral antiepileptic drugs rather than adrenocorticotropic hormone (P < 0.002). Those commencing adrenocorticotropic hormone after the price increase were hospitalized significantly longer (5.1 +/- 0.6 days S.D., P < 0.001). Treatment choices need to be evidence-based, but other factors often influence them.

  15. Isolated adrenocorticotropic hormone deficiency development during chemotherapy for gastric cancer: a case report

    PubMed Central

    2014-01-01

    Introduction Isolated adrenocorticotropic hormone deficiency is an endocrinological disorder characterized by loss of adrenocorticotropic hormone and resultant adrenal insufficiency. Affected patients often present with fatigue, anorexia, and hyponatremia. Although the number of reported cases has been recently increasing, isolated adrenocorticotropic hormone deficiency combined with malignant neoplasia is very rare. Here we describe a patient with gastric cancer who developed unexpected isolated adrenocorticotropic hormone deficiency during chemotherapy. Case presentation A 72-year-old Japanese man was admitted to our hospital because of febrile neutropenia due to chemotherapy for gastric cancer recurrence. Although the neutropenia and fever immediately improved, he became unable to take any oral medications and was bedridden 1 week after admission. His serum sodium level abruptly decreased to 122mEq/L on the fifth day of hospitalization. We performed endocrinological studies to investigate the cause of his hyponatremia and plasma hyposmolality. His plasma adrenocorticotropic hormone and cortisol levels were very low. However, his serum levels of all other anterior pituitary hormones were slightly elevated. We then performed a corticotropin-releasing hormone test, which showed that neither his plasma adrenocorticotropic hormone nor cortisol level responded to corticotropin-releasing hormone stimulation. We definitively diagnosed isolated adrenocorticotropic hormone deficiency based on these findings. Hydrocortisone replacement therapy was begun at 20mg/day, resulting in a marked improvement in his anorexia and general fatigue within a few days. His serum sodium level was also normalized immediately after the administration of hydrocortisone. He was discharged from our hospital on the 50th day of hospitalization. Conclusions The present case is the second report of a patient with concurrent isolated adrenocorticotropic hormone deficiency and gastric cancer and the

  16. Seasonal and sex differences in responsiveness to adrenocorticotropic hormone contribute to stress response plasticity in red-sided garter snakes (Thamnophis sirtalis parietalis).

    PubMed

    Dayger, Catherine A; Lutterschmidt, Deborah I

    2016-04-01

    As in many vertebrates, hormonal responses to stress vary seasonally in red-sided garter snakes (Thamnophis sirtalis parietalis). For example, males generally exhibit reduced glucocorticoid responses to a standard stressor during the spring mating season. We asked whether variation in adrenal sensitivity to adrenocorticotropic hormone (ACTH) explains why glucocorticoid responses to capture stress vary with sex, season and body condition in red-sided garter snakes. We measured glucocorticoids at 0, 1 and 4 h after injection with ACTH (0.1 IU g(-1)body mass) or vehicle in males and females during the spring mating season and autumn pre-hibernation period. Because elevated glucocorticoids can influence sex steroids, we also examined androgen and estradiol responses to ACTH. ACTH treatment increased glucocorticoids in both sexes and seasons. Spring-collected males had a smaller integrated glucocorticoid response to ACTH than autumn-collected males. The integrated glucocorticoid response to ACTH differed with sex during the spring, with males having a smaller glucocorticoid response than females. Although integrated glucocorticoid responses to ACTH did not vary with body condition, we observed an interaction among season, sex and body condition. In males, ACTH treatment did not alter androgen levels in either season, but androgen levels decreased during the sampling period. Similar to previous studies, plasma estradiol was low or undetectable during the spring and autumn, and therefore any effect of ACTH treatment on estradiol could not be determined. These data provide support for a mechanism that partly explains how the hypothalamus-pituitary-adrenal (HPA) axis integrates information about season, sex and body condition: namely, variation in adrenal responsiveness to ACTH.

  17. Adrenocorticotropic Hormone and PI3K/Akt Inhibition Reduce eNOS Phosphorylation and Increase Cortisol Biosynthesis in Long-Term Hypoxic Ovine Fetal Adrenal Cortical Cells.

    PubMed

    Newby, Elizabeth A; Kaushal, Kanchan M; Myers, Dean A; Ducsay, Charles A

    2015-08-01

    This study was designed to determine the role of the MEK/ERK1/2 and PI3K/Akt pathways in cortisol production and endothelial nitric oxide synthase (eNOS) phosphorylation (peNOS) in the ovine fetal adrenal in response to long-term hypoxia (LTH). Pregnant ewes were maintained at high altitude (3820 m) for the last 100 days of gestation (dGa). At 138 to 142 dGa, fetal adrenal cortical cells (FACs) were collected from LTH and age-matched normoxic fetuses. Cortisol production and peNOS were measured in response to pretreatment with the MEK/ERK1/2 pathway inhibitor UO126 (UO) and adrenocorticotropic hormone (ACTH) stimulation. UO126 reduced ACTH-stimulated cortisol in both normoxic and LTH FACs. UO126 alone or in combination with ACTH reduced peNOS in the normoxic group, while ACTH alone or ACTH + UO inhibited peNOS in LTH FACs. Additionally, cortisol was measured in response to pretreatment with UO and treatment with 22R-hydroxycholesterol (22R-OHC) or water-soluble cholesterol (WSC) with and without ACTH stimulation. UO126 had no effect on 22R-OHC-treated cells, but reduced cortisol in cells treated with WSC and/or ACTH. Cortisol and peNOS were also measured in response to pretreatment with PI3K/Akt pathway inhibitor Wortmannin (WT) and ACTH stimulation. Wortmannin further increased cortisol under ACTH-stimulated conditions and, like ACTH, reduced peNOS in LTH but not normoxic FACs. Together, these data suggest that in LTH FACs MEK/ERK1/2 does not regulate peNOS but that UO acts downstream from eNOS, possibly at cholesterol transport, to affect cortisol production in LTH FACs, while the PI3K/Akt pathway, along with ACTH, regulates peNOS and plays a role in the fetal adaptation to LTH in FACs.

  18. Adrenocorticotropic hormone versus prednisolone in the treatment of infantile spasms post vigabatrin failure.

    PubMed

    Jones, Kevin; Snead, O Carter; Boyd, Jennifer; Go, Cristina

    2015-04-01

    The Child Neurology Society/American Academy of Neurology practice parameter has recommended adrenocorticotropic hormone or vigabatrin in the short-term treatment of infantile spasms. When vigabatrin is unavailable or ineffective and adrenocorticotropic hormone is not a treatment option because of the prohibitive cost, other forms of corticosteroids have been considered in the treatment of infantile spasms. This retrospective study reviewed the Hospital for Sick Children's experience with the short-term effectiveness of prednisolone versus adrenocorticotropic hormone in patients with infantile spasms who have failed vigabatrin. The results showed that while adrenocorticotropic hormone was more likely to lead to short-term spasm freedom, there was no difference in the likelihood of longer-term spasm resolution without relapse. These findings can guide clinicians in the treatment of infantile spasms post vigabatrin failure.

  19. Effects of cortisol secreted via a 12-h infusion of adrenocorticotropic hormone on mineral homeostasis and bone metabolism in ovariectomized cows.

    PubMed

    Kim, D; Yamagishi, N; Devkota, B; Furuhama, K

    2012-10-01

    To evaluate the effects of endogenously secreted cortisol on mineral homeostasis and bone metabolism in cows, 4 ovariectomized Holstein cows were infused for 12 h with either an adrenocorticotropic hormone (ACTH) solution (0.5 mg/2 L isotonic NaCl solution per cow) or isotonic NaCl solution in a 2×2 crossover design. ACTH infusion stimulated cortisol secretion and increased plasma cortisol concentrations for 18 h (P<0.001), leading to an elevated plasma glucose concentration until 36 h (P<0.001). Plasma calcium and magnesium concentrations in ACTH-infused cows fluctuated within normal ranges, whereas hypophosphatemia was observed unequivocally. The biochemical bone resorption markers tartrate-resistant acid phosphatase 5b and hydroxyproline decreased following ACTH infusion (P<0.001 and P=0.003, respectively). Similarly, the bone formation marker, bone-specific alkaline phosphatase, decreased continuously until 72 h after the ACTH infusion (P<0.001). These results demonstrate that increased secretion of cortisol via a 12-h ACTH infusion disrupted homeostasis of inorganic phosphate and suppressed bone metabolism in ovariectomized cows without involving gonadal steroid hormones.

  20. Sensitivity of adrenal glands to adrenocorticotropic hormone in animals with alimentary obesity.

    PubMed

    Pankina, T V; Kuzminova, O I; Selyatitskaya, V G

    2008-12-01

    Blood concentration of corticosterone in obese rats did not differ from the control value. In vitro synthesis of progesterone and corticosterone in adrenal slices from obese rats was lower compared to control animals, but these differences disappeared after addition of adrenocorticotropic hormone to the incubation medium. In obese rats, blood content of corticosterone in response to administration of adrenocorticotropic hormone in vivo increased by 8 times, while in control animals this parameter increased by only 4.5 times.

  1. Blood plasma collected after adrenocorticotropic hormone administration during the preovulatory period in the sow negatively affects in vitro fertilization by disturbing spermatozoa function.

    PubMed

    González, R; Kumaresan, A; Bergqvist, A S; Sjunnesson, Y C B

    2015-04-15

    Successful fertilization is essential for reproduction and might be negatively affected by stressful events, which could alter the environment where fertilization occurs. The aim of the study was to determine whether an altered hormonal profile in blood plasma caused by adrenocorticotropic hormone (ACTH) administration could affect in vitro fertilization in the pig model. In experiment 1, gametes were exposed for 24 hours to plasma from ACTH-treated, non-ACTH-treated sows, or medium with BSA. Fertilization, cleavage, and blastocyst rates were lower in the ACTH group compared with the no ACTH or BSA control groups (P < 0.01). In experiment 2, the exposure of matured oocytes for 1 hour before fertilization to the same treatments did not have an impact on their ability to undergo fertilization or on embryo development. In experiment 3, spermatozoa were incubated for 0, 1, 4, and 24 hours under the same conditions. There was no effect of treatment on sperm viability. The percentage of acrosome-reacted spermatozoa remained higher in the ACTH group compared with the non-ACTH-treated group through the incubation period (P < 0.001). Protein tyrosine phosphorylation (PTP) patterns were also affected by treatment (P < 0.001). The presence of an atypical PTP pattern was higher in the ACTH group at all the analyzed time points compared with the BSA and no ACTH groups (P < 0.001). In conclusion, this altered environment may not affect oocyte competence but might affect the sperm fertilizing ability through alterations in the acrosome reaction and correct sequence of PTP patterns.

  2. Role of ACTH and Other Hormones in the Regulation of Aldosterone Production in Primary Aldosteronism

    PubMed Central

    El Ghorayeb, Nada; Bourdeau, Isabelle; Lacroix, André

    2016-01-01

    The major physiological regulators of aldosterone production from the adrenal zona glomerulosa are potassium and angiotensin II; other acute regulators include adrenocorticotropic hormone (ACTH) and serotonin. Their interactions with G-protein coupled hormone receptors activate cAMP/PKA pathway thereby regulating intracellular calcium flux and CYP11B2 transcription, which is the specific steroidogenic enzyme of aldosterone synthesis. In primary aldosteronism (PA), the increased production of aldosterone and resultant relative hypervolemia inhibits the renin and angiotensin system; aldosterone secretion is mostly independent from the suppressed renin–angiotensin system, but is not autonomous, as it is regulated by a diversity of other ligands of various eutopic or ectopic receptors, in addition to activation of calcium flux resulting from mutations of various ion channels. Among the abnormalities in various hormone receptors, an overexpression of the melanocortin type 2 receptor (MC2R) could be responsible for aldosterone hypersecretion in aldosteronomas. An exaggerated increase in plasma aldosterone concentration (PAC) is found in patients with PA secondary either to unilateral aldosteronomas or bilateral adrenal hyperplasia (BAH) following acute ACTH administration compared to normal individuals. A diurnal increase in PAC in early morning and its suppression by dexamethasone confirms the increased role of endogenous ACTH as an important aldosterone secretagogue in PA. Screening using a combination of dexamethasone and fludrocortisone test reveals a higher prevalence of PA in hypertensive populations compared to the aldosterone to renin ratio. The variable level of MC2R overexpression in each aldosteronomas or in the adjacent zona glomerulosa hyperplasia may explain the inconsistent results of adrenal vein sampling between basal levels and post ACTH administration in the determination of source of aldosterone excess. In the rare cases of glucocorticoid remediable

  3. A possible analytical and clinical role of endogenous antibodies causing discrepant adrenocorticotropic hormone measurement in a case of ectopic Cushing's syndrome.

    PubMed

    Saiegh, Leonard; Odeh, Majed; Chen-Konak, Limor; Elias, Nizar; Sheikh-Ahmad, Mohammad; Reut, Maria; Slobodin, Gleb; Bejar, Jacob; Shechner, Carmela

    2014-07-01

    Heterophilic antibodies are well described, but poorly appreciated interferents and is often not a recognized problem affecting most immunoassays. We report a patient presented with ectopic Cushing's syndrome (CS), but repeated plasma adrenocorticotropic hormone (ACTH) concentrations conducted by immunoassay were inappropriately within the reference range and not elevated, most probably as a result of antibody interference. A 36-year-old woman, presented with large gastric neuroendocrine carcinoma and severe ectopic CS, while repeated plasma ACTH concentrations conducted by immunoassay were inappropriately within the reference range. As we expected ACTH concentration to be higher, we performed several tests to evaluate whether there was any assay interference causing falsely lower than expected ACTH results. We measured ACTH using a different immunoassay, assayed the sample in dilution, assayed the sample after being incubated in heterophilic antibody blocking agent tube and performed recovery studies. Tests indicated the presence of interfering compounds, most probably heterophilic antibodies. When clinicians find ACTH concentrations to be lower than expected, we recommend the laboratory investigate antibody interference.

  4. Influence of feeding status, time of the day, and season on baseline adrenocorticotropic hormone and the response to thyrotropin releasing hormone-stimulation test in healthy horses.

    PubMed

    Diez de Castro, E; Lopez, I; Cortes, B; Pineda, C; Garfia, B; Aguilera-Tejero, E

    2014-07-01

    Equine pituitary pars intermedia function can be assessed by the measurement of baseline and thyrotropin releasing hormone (TRH)-induced concentrations of adrenocorticotropic hormone (ACTH); however, these measurements may be affected by the environment. Therefore, a prospective observational study evaluated the influence of feeding, time of the day, and season on baseline and TRH-induced concentrations of ACTH in healthy horses. Baseline ACTH was measured in 50 horses before and 2 h after feeding. Six research horses were subjected to a crossover study in which 6 TRH tests were performed in 2 different seasons, March-April (MA) and July-September (JS), at 2 different times of the day, 8 AM and 8 PM, and, under 2 different conditions relative to feeding status, fasted and 2 h after feeding. Differences between fasted and fed horses were found in baseline ACTH, 17.1 ± 1.8 versus 46.1 ± 7.6 pg/mL (P = 0.003) and TRH-stimulated ACTH: 124.1 ± 21.3 versus 192.6 ± 33.1 pg/mL (P = 0.029) at 10 min, and 40.1 ± 4.9 versus 73.2 ± 13.4 pg/mL (P = 0.018) at 30 min post TRH injection. No differences were found between tests performed at different times of the day. Basal ACTH concentrations were greater in JS than in MA, 17.1 ± 1.8 versus 11.9 ± 0.6 pg/mL (P = 0.006). A seasonal influence was also found in stimulated ACTH values, which were much greater in JS 122.7 ± 36.7 versus 31.2 ± 7.4 pg/mL, at 10 min (P = 0.03) and 39.0 ± 7.2 versus 19.8 ± 3.1 pg/mL, at 30 min (P = 0.03). In addition to season, feeding is a potential confounding factor when measuring baseline or stimulated ACTH in horses. In conclusion, feeding status should be standardized for the diagnosis of equine pituitary pars intermedia dysfunction.

  5. Reduction in glutamine/glutamate levels in the cerebral cortex after adrenocorticotropic hormone therapy in patients with west syndrome.

    PubMed

    Munakata, Mitsutoshi; Togashi, Noriko; Sakamoto, Osamu; Haginoya, Kazuhiro; Kobayashi, Yasuko; Onuma, Akira; Iinuma, Kazuie; Kure, Shigeo

    2014-01-01

    West syndrome (WS), an intractable epileptic encephalopathy of infancy, is refractory to many antiepileptic drugs; however, adrenocorticotropic hormone (ACTH) is an effective treatment for WS. The mechanism behind the efficacy of ACTH is mediated by biochemical processes that remain unknown. We examined the effects of ACTH therapy with tetracosactide (TCS), a synthetic ACTH analogue, on brain metabolism in patients with WS, using (1)H magnetic resonance spectroscopy (¹H-MRS). In six patients with cryptogenic WS, we performed single-voxel ¹H-MRS at the occipital lobe cortex. Measurements were taken prior to TCS treatment, a few days after therapy, and several months after therapy. Data were also compared with subjects having only mild psychomotor delays. The metabolites measured were glutamine plus glutamate (Glx), N-acetylaspartate (NAA), choline (Cho), and myoinositol (mI); each was expressed as a ratio with creatine plus phosphocreatine (total creatine: tCr). The Glx/tCr ratio was significantly reduced after the TCS treatment. The NAA/tCr ratio was also significantly reduced after the treatment compared with the control group, although the change in NAA signal was heterogeneous among patients, correlating with respective outcomes. The Cho/tCr and mI/tCr ratios were not affected by TCS treatment. The reduction in Glx suggests a decrease in the glutamate-glutamine cycle, which plays a pivotal role in synthesizing neurotransmitters such as glutamate and GABA. TCS-induced Glx reduction may induce changes in synaptic signal transduction, thereby accounting for the effect of TCS on WS. The change in NAA indicates altered neuronal activity, which may be correlated with outcome in WS patients.

  6. Adrenocorticotropic hormone gel in the treatment of systemic lupus erythematosus: A retrospective study of patients.

    PubMed Central

    Li, Xiao; Golubovsky, Josh; Hui-Yuen, Joyce; Shah, Ummara; Olech, Ewa; Lomeo, Rosalia; Singh, Vijay; Busch, Howard; Strandberg, Mary Jane; Strandberg, Kayla; Horowitz, Leslie; Askanase, Anca

    2016-01-01

    Objectives: Acthar Gel is a long-acting formulation of adrenocorticotropic hormone (ACTH) with anti-inflammatory effects thought to be mediated in part through melanocortin receptor activation. This study was initiated to understand the role of Acthar Gel in SLE treatment in rheumatology practices. Methods: This is a retrospective case series of nine adult female patients treated with Acthar Gel for at least six months at five academic centers. Treating physicians completed a one-page questionnaire on lupus medications, disease activity, and outcomes. Clinical response was defined using SLEDAI 2K and improvement in the clinical manifestation(s) being treated. Results: The most common clinical SLE manifestations/indications requiring therapy with Acthar Gel were arthritis, rash, and inability to taper corticosteroids. The mean SLEDAI 2K score at baseline was 5.8 ± 5.0 (range 0-16). Six patients were concomitantly treated with corticosteroids (mean dose 18.3mg/day). All patients were on background SLE medications including immunosuppressives. Seven of nine patients had an overall improvement, with a decrease in SLEDAI 2K from 5.8 ± 5.0 at baseline to 3.5 ± 2.7 (range 0-8); four of five patients had improvement or resolution in arthritis, and one of two patients had resolution of inflammatory rash. Four patients discontinued corticosteroids and one patient tapered below 50% of the initial dose by 3 months of treatment with Acthar Gel. No adverse events were reported. Conclusions: This study suggests a role for Acthar Gel as an alternative to corticosteroids in the treatment of SLE. Acthar Gel appears to be safe and well-tolerated after 6 months of treatment, with a significant reduction in disease activity. PMID:27158444

  7. From Bioinactive ACTH to ACTH Antagonist: The Clinical Perspective

    PubMed Central

    Ghaddhab, Chiraz; Vuissoz, Jean-Marc; Deladoëy, Johnny

    2017-01-01

    The adrenocorticotropic hormone (ACTH) is a pituitary hormone derived from a larger peptide, the proopiomelanocortin (POMC), as are the MSHs (α-MSH, β-MSH, and γ-MSH) and the β-LPH-related polypeptides (Figure 1A). ACTH drives adrenal steroidogenesis and growth of the adrenal gland. ACTH is a 39 amino acid polypeptide that binds and activates its cognate receptor [melanocortin receptor 2 (MC2R)] through the two regions H6F7R8W9 and K15K16R17R18P19. Most POMC-derived polypeptides contain the H6F7R8W9 sequence that is conserved through evolution. This explains the difficulties in developing selective agonists or antagonists to the MCRs. In this review, we will discuss the clinical aspects of the role of ACTH in physiology and disease, and potential clinical use of selective ACTH antagonists. PMID:28228747

  8. Mechanisms of action of adrenocorticotropic hormone and other melanocortins relevant to the clinical management of patients with multiple sclerosis

    PubMed Central

    Berkovich, Regina; Catania, Anna; Lisak, Robert P; Zaidi, Mone

    2013-01-01

    The therapeutic benefits of adrenocorticotropic hormone in multiple sclerosis are usually ascribed to its corticotropic actions. Evidence is presented that adrenocorticotropic hormone, approved for multiple sclerosis relapses, acts via corticosteroid-independent melanocortin pathways to engender down-modulating actions on immune-system cells and the cytokines they synthesize. Immune response-dampening effects are also brought about by agent-induced neurotransmitters that inhibit immunocytes. The likelihood that adrenocorticotropic hormone promotes microglial quiescence and counteracts glucocorticoid-mediated bone resorption is discussed. PMID:23034287

  9. Mechanisms of action of adrenocorticotropic hormone and other melanocortins relevant to the clinical management of patients with multiple sclerosis.

    PubMed

    Arnason, Barry G; Berkovich, Regina; Catania, Anna; Lisak, Robert P; Zaidi, Mone

    2013-02-01

    The therapeutic benefits of adrenocorticotropic hormone in multiple sclerosis are usually ascribed to its corticotropic actions. Evidence is presented that adrenocorticotropic hormone, approved for multiple sclerosis relapses, acts via corticosteroid-independent melanocortin pathways to engender down-modulating actions on immune-system cells and the cytokines they synthesize. Immune response-dampening effects are also brought about by agent-induced neurotransmitters that inhibit immunocytes. The likelihood that adrenocorticotropic hormone promotes microglial quiescence and counteracts glucocorticoid-mediated bone resorption is discussed.

  10. ACTH protects against glucocorticoid-induced osteonecrosis of bone.

    PubMed

    Zaidi, Mone; Sun, Li; Robinson, Lisa J; Tourkova, Irina L; Liu, Li; Wang, Yujuan; Zhu, Ling-Ling; Liu, Xuan; Li, Jianhua; Peng, Yuanzhen; Yang, Guozhe; Shi, Xingming; Levine, Alice; Iqbal, Jameel; Yaroslavskiy, Beatrice B; Isales, Carlos; Blair, Harry C

    2010-05-11

    We report that adrenocorticotropic hormone (ACTH) protects against osteonecrosis of the femoral head induced by depot methylprednisolone acetate (depomedrol). This therapeutic response likely arises from enhanced osteoblastic support and the stimulation of VEGF by ACTH; the latter is largely responsible for maintaining the fine vascular network that surrounds highly remodeling bone. We suggest examining the efficacy of ACTH in preventing human osteonecrosis, a devastating complication of glucocorticoid therapy.

  11. Effect of blood plasma collected after adrenocorticotropic hormone administration during the preovulatory period in the sow on oocyte in vitro maturation.

    PubMed

    González, R; Sjunnesson, Y C B

    2013-10-01

    Reproduction may be affected by stressful events changing the female endocrine or metabolic profile. An altered environment during oocyte development could influence the delicate process of oocyte maturation. Here, the effect of simulated stress by media supplementation with blood plasma from sows after adrenocorticotropic hormone (ACTH) administration during the preovulatory period was assessed. Oocytes were matured for 46 hours in the presence of plasma from ACTH-treated sows, or plasma from NaCl-treated control sows, or medium without plasma (BSA group). The plasma used had been collected at 36 and 12 hours (±2 hours) before ovulation (for the first 24 hours + last 22 hours of maturation, respectively). Subsequent fertilization and embryo development were evaluated. Actin cytoskeleton and mitochondrial patterns were studied by confocal microscopy both in the oocytes and the resulting blastocysts. Nuclear maturation did not differ between treatments. Subtle differences were observed in the actin microfilaments in oocytes; however, mitochondrial patterns were associated with the treatment (P < 0.001). These differences in mitochondrial patterns were not reflected by in vitro outcomes, which were similar in all groups. In conclusion, an altered hormonal environment provided by a brief exposure to plasma from ACTH-treated sows during in vitro oocyte maturation could induce alterations in actin cytoskeleton and mitochondrial patterns in oocytes. However, these changes might not hamper the subsequent in vitro embryo development.

  12. Adrenocorticotropic hormone versus pulsatile dexamethasone in the treatment of infantile epilepsy syndromes.

    PubMed

    Haberlandt, Edda; Weger, Christine; Sigl, Sara Baumgartner; Rauchenzauner, Markus; Scholl-Bürgi, Sabine; Rostásy, Kevin; Karall, Daniela

    2010-01-01

    For treatment of intractable epilepsies, there are no data comparing conventional adrenocorticotropic hormone and pulsatile corticoid therapy with dexamethasone. A retrospective comparison of efficacy was therefore conducted for both forms of application. Between 1989 and 2001, a series of 11 children with West syndrome and 3 with Lennox-Gastaut syndrome were treated with adrenocorticotropic hormone (group 1); between 2003 and 2006, 7 children with West syndrome, 5 with electrical status epilepticus during slow sleep, and 2 with Lennox-Gastaut syndrome were treated with pulsatile corticoid therapy (group 2). In group 1 (n = 14), 9/11 West syndrome patients became seizure free, but none with Lennox-Gastaut syndrome (0/3). In group 2 (n = 14), 4/7 West syndrome patients became seizure-free, 1/2 with Lennox-Gastaut syndrome exhibited seizure-frequency reduction, and 2/5 patients with electrical status epilepticus during slow-wave sleep exhibited significant improvement according to electroencephalograms. In West syndrome, pulsatile corticoid therapy was an effective alternative treatment to adrenocorticotropic hormone, whereas in Lennox-Gastaut syndrome in general steroids did not lead to a significant seizure reduction. In electrical status epilepticus during slow-wave sleep, treatment with pulsatile corticoid therapy seems to be effective and should be investigated in a larger group of patients.

  13. Tipepidine, a non-narcotic antitussive, exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone-treated rats.

    PubMed

    Kawaura, Kazuaki; Ogata, Yukino; Honda, Sokichi; Soeda, Fumio; Shirasaki, Tetsuya; Takahama, Kazuo

    2016-04-01

    We investigated whether tipepidine exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone (ACTH)-treated rats, which is known as a treatment-resistant depression model, and we studied the pharmacological mechanisms of the effects of tipepidine. Male Wistar rats (5-7 weeks old) were used in this study. Tipepidine (20 and 40 mg/kg, i.p.) decreased the immobility time in the forced swimming test in ACTH-treated rats. The anti-immobility effect of tipepidine was blocked by a catecholamine-depleting agent, alpha-methyl-p-tyrosine (300 mg/kg, s.c.), but not by a serotonin-depleting agent, p-chlorophenylalanine. The anti-immobility effect of tipepidine was also blocked by a dopamine D1 receptor antagonist, SCH23390 (0.02 mg/kg, s.c.) and an adrenaline α2 receptor antagonist, yohimbine (2 mg/kg, i.p.). In microdialysis technique, tipepidine (40 mg/kg, i.p.) increased the extracellular dopamine level of the nucleus accumbens (NAc) in ACTH-treated rats. These results suggest that tipepidine exerts an antidepressant-like effect in the forced swimming test in ACTH-treated rats, and that the effect of tipepidine is mediated by the stimulation of dopamine D1 receptors and adrenaline α2 receptors. The results also suggest that an increase in the extracellular dopamine level in the NAc may be involved in the antidepressant-like effect of tipepidine in ACTH-treated rats.

  14. Mu-opioid receptor A118G polymorphism in healthy volunteers affects hypothalamic-pituitary-adrenal axis adrenocorticotropic hormone stress response to metyrapone.

    PubMed

    Ducat, Elizabeth; Ray, Brenda; Bart, Gavin; Umemura, Yoshie; Varon, Jack; Ho, Ann; Kreek, Mary Jeanne

    2013-03-01

    The mu-opioid receptor encoded by the gene OPRM1 plays a primary role in opiate, alcohol, cocaine and nicotine addiction. Studies using opioid antagonists demonstrate that the mu-opioid receptor (MOP-r) also mediates the hypothalamic-pituitary-adrenal (HPA) axis stress response. A common polymorphism in exon one of the MOP-r gene, A118G, has been shown to significantly alter receptor function and MOP-r gene expression; therefore, this variant likely affects HPA-axis responsivity. In the current study, we have investigated whether the presence of the 118AG variant genotype affects HPA axis responsivity to the stressor metyrapone, which transiently blocks glucocorticoid production in the adrenal cortex. Forty-eight normal and healthy volunteers (32 men, 16 women) were studied, among whom nine men and seven women had the 118AG genotype. The 118G allele blunted the adrenocorticotropic hormone (ACTH) response to metyrapone. Although there was no difference in basal levels of ACTH, subjects with the 118AG genotype had a more modest rise and resultant significantly lower ACTH levels than those with the prototype 118AA at the 8-hour time point (P < 0.02). We found no significant difference between genders. These findings suggest a relatively greater tonic inhibition at hypothalamic-pituitary sites through the mu-opioid receptor and relatively less cyclical glucocorticoid inhibition in subjects with the 118G allele.

  15. Mapping the human melanocortin 2 receptor (adrenocorticotropic hormone receptor; ACTHR) gene (MC2R) to the small arm of chromosome 18 (18p11. 21-pter)

    SciTech Connect

    Vamvakopoulos, N.C.; Chrousos, G.P. ); Rojas, K.; Overhauser, J. ); Durkin, A.S.; Nierman, W.C. )

    1993-11-01

    The human adrenocorticotropic hormone receptor (ACTHR) was recently cloned and shown to belong to the superfamily of membrane receptors that couple to guanine nucleotide-binding proteins and adenylyl cyclase. A genetically heterogeneous (including both X-linked and autosomally recessive forms) congenital syndrome of general hereditary adrenal unresponsiveness to ACTH has been documented in several kindreds. This inherited defect affects one of the steps in the cascade of events of ACTH action on glucocorticoid biosynthesis, without altering mineralocorticoid productions. Since candidate targets for pathophysiological manifestations of deficient responsiveness to ACTH include lesions of the ACTHR gene, the authors undertook to map it to a chromosomal location. They first used polymerase chain reaction (PCR) amplification of NIGMS Panel 1 DNA template to assign a 960-bp-long fragment of the human ACTHR gene to chromosome 18. Subsequently, they determined the location of the ACTHR gene within human chromosome 18 by PCR amplification of genomic DNA template from somatic cell hybrids that contain deletions of this chromosome.

  16. Using the failure mode and effects analysis model to improve parathyroid hormone and adrenocorticotropic hormone testing

    PubMed Central

    Magnezi, Racheli; Hemi, Asaf; Hemi, Rina

    2016-01-01

    Background Risk management in health care systems applies to all hospital employees and directors as they deal with human life and emergency routines. There is a constant need to decrease risk and increase patient safety in the hospital environment. The purpose of this article is to review the laboratory testing procedures for parathyroid hormone and adrenocorticotropic hormone (which are characterized by short half-lives) and to track failure modes and risks, and offer solutions to prevent them. During a routine quality improvement review at the Endocrine Laboratory in Tel Hashomer Hospital, we discovered these tests are frequently repeated unnecessarily due to multiple failures. The repetition of the tests inconveniences patients and leads to extra work for the laboratory and logistics personnel as well as the nurses and doctors who have to perform many tasks with limited resources. Methods A team of eight staff members accompanied by the Head of the Endocrine Laboratory formed the team for analysis. The failure mode and effects analysis model (FMEA) was used to analyze the laboratory testing procedure and was designed to simplify the process steps and indicate and rank possible failures. Results A total of 23 failure modes were found within the process, 19 of which were ranked by level of severity. The FMEA model prioritizes failures by their risk priority number (RPN). For example, the most serious failure was the delay after the samples were collected from the department (RPN =226.1). Conclusion This model helped us to visualize the process in a simple way. After analyzing the information, solutions were proposed to prevent failures, and a method to completely avoid the top four problems was also developed. PMID:27980440

  17. Placental corticotropin-releasing hormone may be a stimulator of maternal pituitary adrenocorticotropic hormone secretion in humans.

    PubMed Central

    Sasaki, A; Shinkawa, O; Yoshinaga, K

    1989-01-01

    To clarify the physiological role of placental corticotropin-releasing hormone (CRH), we measured plasma CRH, ACTH, and cortisol throughout pregnancy. Cerebrospinal fluid (CSF) CRH levels and ACTH responsiveness to synthetic CRH were also quantified in pregnant and nonpregnant women. Maternal plasma CRH levels, which increased progressively during pregnancy, correlated well with both ACTH and cortisol in early labor, delivery, and postpartum samples, and also with cortisol levels in samples before labor. CSF CRH levels in term pregnant women did not differ from those of nonpregnant women. CRH infusion that attained similar plasma CRH levels to those found in late pregnancy elicited significant ACTH release in vivo and regular CRH test provoked normal ACTH response during early pregnancy but no response during late pregnancy. We concluded that: (a) maternal pituitary-adrenal axis correlates well with plasma CRH levels, which are high enough to provoke ACTH release from maternal pituitary; (b) hypothalamic CRH secretion in term pregnant women is not exaggerated; and (c) maternal pituitary is responsive to synthetic CRH in early but not late pregnancy, suggesting that maternal pituitary-adrenal axis is already activated by high circulating CRH. Placental CRH may be an important stimulator of the maternal pituitary-adrenal axis during pregnancy. Images PMID:2556451

  18. EDTA interference in electrochemiluminescence ACTH assay.

    PubMed

    Toprak, Burak; Yalcin, Hulya; Arı, Elif; Colak, Ayfer

    2016-11-01

    Background As plasma is the recommended sample type for Roche adrenocorticotropic hormone (ACTH) assay, we evaluated the effect of EDTA concentration on Cobas ACTH assay. Methods Samples containing twofold and fourfold higher concentrations of EDTA were prepared by adding plasma to empty K2EDTA tubes and by making under-filled EDTA tubes. All measurements were performed with four replicates. Results Increased EDTA concentration resulted in a significant decrease in ACTH concentration. Fifty-per cent-filled EDTA tube showed 19% decrease in ACTH concentration and 25% filled EDTA tube showed 50% decrease in ACTH concentration. Conclusion We recommend that inadequately filled EDTA specimens should be rejected when using Cobas ACTH assay.

  19. Adrenocorticotropic hormone but not high-density lipoprotein cholesterol or salivary cortisol was a predictor of adrenal insufficiency in patients with septic shock.

    PubMed

    Festti, Josiane; Grion, Cintia Magalhães Carvalho; Festti, Luciana; Mazzuco, Tânia Longo; Lima-Valassi, Helena Pantelion; Brito, Vinícius Nahime; Barbosa, Décio Sabbatini; Carrilho, Alexandre José Faria

    2014-07-01

    Relative adrenal insufficiency in sepsis has been extensively debated on; however, accurate diagnosis and therapeutic intervention remain controversial. The authors aimed to evaluate adrenocorticotropic hormone (ACTH), salivary cortisol, total cortisol and estimated plasma-free cortisol, cholesterol, and lipoproteins as predictors of adrenal insufficiency in patients within 24 h of septic shock diagnosis. This prospective study evaluated all hospitalized patients older than 18 years who developed septic shock and were using vasoactive drugs within 24 h of diagnosis. Blood and saliva samples were drawn at baseline and 60 min (T60) after 250 μg tetracosactide intravenous injection. Patients were divided into two groups: responders (Δ [T60 minus baseline] total cortisol >9 μg/dL) and nonresponders (Δ total cortisol ≤ 9 μg/dL or baseline total cortisol <10 μg/dL). The latter group was considered to have adrenal insufficiency. A total of 7,324 hospitalized patients were monitored, and 34 subjects with septic shock were included in the analysis. Adrenal insufficiency was found in 32.4%. Total cholesterol, high-density lipoprotein cholesterol, triglycerides, and salivary cortisol did not differ between groups. Estimated plasma-free cortisol was not better than total plasma cortisol in estimating adrenal function. Baseline endogenous ACTH was higher in nonresponders than responders (55.5 pg/mL vs. 18.3 pg/mL, respectively; P = 0.01). The cutoff ACTH value that discriminated patients with adrenal insufficiency was 31.5 pg/mL. Thus, endogenous ACTH measured within 24 h of septic shock diagnosis could predict adrenal response to tetracosactide.

  20. Paraneoplastic Dermatomyositis with Cutaneous and Myopathic Disease Responsive to Adrenocorticotropic Hormone Therapy

    PubMed Central

    Mancuso, Christopher; Lal, Karan; Dicostanzo, Damian; Gropper, Charles

    2017-01-01

    Dermatomyositis is a myopathic or amyopathic autoimmune connective tissue disease that presents with classic dermatologic findings ranging from: poikilodermatous photosensitivity (shawl sign), eyelid edema and violaceous-pigmentation (heliotrope sign), lichenoid eruptions on the knuckles and elbows (Gottron’s sign), periungual telangiectasias, and ragged cuticles (Samitz sign). Up to 30 percent of adult-onset cases of dermatomyositis may represent a paraneoplastic syndrome warranting a thorough work-up for malignancy. The authors present a case report of paraneoplastic dermatomyositis associated with triple negative, BRCA-1 positive, invasive intraductal carcinoma of the breast, whose myopathic and cuteanous symptoms were recalcitrant to high-dose corticosteroid therapy. Herein, the authors describe the first reported case of the use of an injectable adrenocorticotropic hormone agonist gel in a patient with myopathic paraneoplastic disease that achieved clinical resolution of both myopathic and cutaneous symptoms, but subseuqently developed significant hyperpigmentation of her face suspected to be secondary to a chemotherapeutic-induced pigmentary change which was augmented by adrenocorticotropic hormone therapy. PMID:28210382

  1. Isolated adrenocorticotropic hormone deficiency due to probable lymphocytic hypophysitis in a woman

    PubMed Central

    Kacem, Faten Hadj; Charfi, Nadia; Mnif, Mouna Feki; Kamoun, Mahdi; Akid, Faouzi; Mnif, Fatma; Naceur, Basma Ben; Rekik, Nabila; Mnif, Zainab; Abid, Mohamed

    2013-01-01

    We report a 22-year-old woman who presented with asthenia, weight loss and hypotension in which extensive pituitary and adrenal investigations were diagnostic of isolated adrenocorticotropic hormone deficiency (IAD) of pituitary origin. Magnetic resonance imaging of the hypothalamus and pituitary showed a normal-sized pituitary, with no mass lesion. The diagnosis of IAD probably secondary to lymphocytic hypophysitis (LYH) was made. IAD is able to be the way of presentation of LYH, although the disease could or could not turn into a panhypopituitarism. Prompt recognition of this potentially fatal condition is important because of the availability of effective treatment. Indeed, regular endocrine and imaging follow up is important for patients with IAD and normal initial pituitary imaging results to detect early new-onset pituitary hormones deficiencies or imaging abnormalities. PMID:24251125

  2. Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS.

    PubMed

    Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R; Changelian, Armen; Laws, Edward R; Santagata, Sandro; Agar, Nathalie Y R; Van Berkel, Gary J

    2015-08-01

    Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections, using a fully automated droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS system for spatially resolved sampling, HPLC separation, and mass spectrometric detection. Excellent correlation was found between the protein distribution data obtained with this method and data obtained with matrix-assisted laser desorption/ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland. AVP was most abundant in the posterior pituitary gland region (neurohypophysis), and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH-secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH-secreting adenomas and in normal anterior adenohypophysis compared with non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis, as expected. This work reveals that a fully automated droplet-based liquid-microjunction surface-sampling system coupled to HPLC-ESI-MS-MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, including AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity, and specificity of this method support the potential of this basic technology, with further advancement, for assisting surgical decision-making. Graphical Abstract Mass spectrometry based profiling of hormones in human pituitary gland and tumor thin tissue sections.

  3. Localization of the genes encoding the melanocortin-2 (Adrenocorticotropic hormone) and melanocortin-3 receptors to chromosomes 18p11. 2 and 20q13. 2-q13. 3 by fluorescence in situ hybridization

    SciTech Connect

    Gantz, I.; Tashiro, Takao; Konda, Yoshitaka; Shimoto, Yoshimasa; Miwa, Hiroto; Munzert, G.; Barcroft, C.; Glover, T.; Yamada, Tadataka )

    1993-10-01

    Adrenocorticotropic hormone (ACTH) and [alpha]-, [beta]-, and [gamma]-melanocyte-stimulating hormone (MSH) are products of propiomelanocortin post-translational processing. These compounds are collectively labeled as melanocortins (MC). Aside from their established effects on the regulation of the adrenal cortex (ACTH) and melanocytes ([alpha]-MSH), the melanocortins have been implicated in a broad array of physiological events. Melanocortins mediate their effects through cell membrane receptors belonging to the superfamily of seven transmembrane G-protein-linked receptors. Using the technique of polymerase chain reaction with primers based on conserved areas of the seven transmembrane G-protein-linked receptor family, the authors recently isolated an [open quotes]orphan[close quotes] subfamily of this receptor group. Within the past year, two of these receptors were identified as specific for [alpha]-MSH (MC1) and ACTH (MC2). They have recently described a third melanocortin receptor (MC3) that appears to recognize the core heptapeptide sequence of melanocortins with equal potency and efficacy and identified its presence in the brain, placenta, and gut. Using the FISH technique, they localized the ACTH and the melanocortin-3 receptors to chromosome loci 18p11.2 and 20q12.3-q13.2, respectively. 19 refs., 1 fig.

  4. Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC–ESI-MS–MS

    DOE PAGES

    Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R.; ...

    2015-06-18

    Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections using a fully automated droplet-based liquid microjunction surface sampling-HPLC-ESI-MS/MS system for spatially resolved sampling, HPLC separation, and mass spectral detection. Excellent correlation was found between the protein distribution data obtained with this droplet-based liquid microjunction surface sampling-HPLC-ESI-MS/MS system and those data obtained with matrix assisted laser desorption ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland.more » AVP was most abundant in the posterior pituitary gland region (neurohypophysis) and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH secreting adenomas and in normal anterior adenohypophysis compared to non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis as anticipated. This work demonstrates that a fully automated droplet-based liquid microjunction surface sampling system coupled to HPLC-ESI-MS/MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, such as AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity and specificity of the current methodology support the potential of this basic technology with further advancement for assisting surgical decision-making.« less

  5. Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC–ESI-MS–MS

    SciTech Connect

    Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R.; Changelian, Armen; Laws, Edward R.; Santagata, Sandro; Agar, Nathalie Y. R.; Van Berkel, Gary J.

    2015-06-18

    Described here are the results from the profiling of the proteins arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) from normal human pituitary gland and pituitary adenoma tissue sections using a fully automated droplet-based liquid microjunction surface sampling-HPLC-ESI-MS/MS system for spatially resolved sampling, HPLC separation, and mass spectral detection. Excellent correlation was found between the protein distribution data obtained with this droplet-based liquid microjunction surface sampling-HPLC-ESI-MS/MS system and those data obtained with matrix assisted laser desorption ionization (MALDI) chemical imaging analyses of serial sections of the same tissue. The protein distributions correlated with the visible anatomic pattern of the pituitary gland. AVP was most abundant in the posterior pituitary gland region (neurohypophysis) and ATCH was dominant in the anterior pituitary gland region (adenohypophysis). The relative amounts of AVP and ACTH sampled from a series of ACTH secreting and non-secreting pituitary adenomas correlated with histopathological evaluation. ACTH was readily detected at significantly higher levels in regions of ACTH secreting adenomas and in normal anterior adenohypophysis compared to non-secreting adenoma and neurohypophysis. AVP was mostly detected in normal neurohypophysis as anticipated. This work demonstrates that a fully automated droplet-based liquid microjunction surface sampling system coupled to HPLC-ESI-MS/MS can be readily used for spatially resolved sampling, separation, detection, and semi-quantitation of physiologically-relevant peptide and protein hormones, such as AVP and ACTH, directly from human tissue. In addition, the relative simplicity, rapidity and specificity of the current methodology support the potential of this basic technology with further advancement for assisting surgical decision-making.

  6. A harmful traditional practice in newborns with adrenocorticotropic hormone resistance syndrome: branding

    PubMed Central

    Baştuğ, Osman; Korkmaz, Levent; Korkut, Sabriye; Halis, Hülya; Güneş, Tamer; Kurtoğlu, Selim

    2016-01-01

    Branding refers to a traditional practice of creating ‘therapeutic’ burns with hot iron rods over the skin in order to treat various diseases. Although branding is a harmful practice for the body, it has been used for various illnesses including physiologic jaundice in newborns, pneumonia, and convulsions. It causes serious morbidity and delays seeking proper medical care in neonates. Innovations of modern medicine and the use of evidence-based medicine should be preferred instead of these traditional practices. We present a branded mature newborn baby who was diagnosed as having adrenocorticotropic hormone resistance syndrome. This problem is very rare in Turkey; however, it is a very important health issue and has social aspects. Therefore, this case is presented to increase awareness. PMID:28123337

  7. A harmful traditional practice in newborns with adrenocorticotropic hormone resistance syndrome: branding.

    PubMed

    Baştuğ, Osman; Korkmaz, Levent; Korkut, Sabriye; Halis, Hülya; Güneş, Tamer; Kurtoğlu, Selim

    2016-12-01

    Branding refers to a traditional practice of creating 'therapeutic' burns with hot iron rods over the skin in order to treat various diseases. Although branding is a harmful practice for the body, it has been used for various illnesses including physiologic jaundice in newborns, pneumonia, and convulsions. It causes serious morbidity and delays seeking proper medical care in neonates. Innovations of modern medicine and the use of evidence-based medicine should be preferred instead of these traditional practices. We present a branded mature newborn baby who was diagnosed as having adrenocorticotropic hormone resistance syndrome. This problem is very rare in Turkey; however, it is a very important health issue and has social aspects. Therefore, this case is presented to increase awareness.

  8. Isolated ACTH deficiency in a patient with empty sella as revealed by severe hyponatremia.

    PubMed

    Doroftei, Nicoleta Alina; de Rudder, Catherine; de Visscher, Nathalie; Hanon, Francois

    2016-12-01

    Hyponatremia due to isolated adrenocorticotropic hormone (ACTH) deficiency is difficult to diagnose as it is usually indistinguishable from non-endocrine syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present a case secondary to empty sella. Most patients with empty sella remain asymptomatic throughout life and require no treatment; however, in cases involving the development of isolated ACTH deficiency, corticosteroid treatment should be enforced to avoid fatal consequences.

  9. Sellar gangliocytoma with adrenocorticotropic and prolactin adenoma.

    PubMed

    Kissiedu, Juliana O; Prayson, Richard A

    2016-02-01

    We report a case of a 60-year-old man who presented with weight gain, headaches, dizziness, erectile dysfunction and decreased libido. He was found to have elevated adrenocorticotropic hormone (ACTH) and prolactin serum levels. The imaging studies revealed a 1.4 cm sella/suprasellar mass which was compressing the optic chiasm. Histologic slides of the lesion showed a pituitary adenoma, marked by a proliferation of biphenotypic appearing cells, associated with a gangliocytoma, and marked by a proliferation of atypical appearing neuronal cells arranged against a glial-appearing background. Pituitary adenoma-gangliocytomas are benign combination tumors that rarely occur in the sellar region. Adenomas in this setting are sometimes functional, and rare patients with mixed adenomas (adenomas secreting more than one hormone) have been reported. To our knowledge, there has been only one other report of a combined ACTH and prolactin-producing adenoma with gangliocytoma, reported in a patient who also had acromegaly. In our patient, the immunohistochemical stains demonstrated that the bulk of the adenoma cells stained with prolactin antibody, and scattered clusters of cells within the adenoma stained positively for ACTH. The adenoma did not stain with antibodies to any of the other anterior pituitary hormones. Postoperatively, the elevated prolactin and ACTH levels returned to normal levels and there was no evidence of residual tumor. Adequate sampling and immunohistochemistry are important in rendering a correct diagnosis and in identifying the hormone status of mixed adenoma-gangliocytomas.

  10. Aberrant luteinizing hormone-releasing hormone-stimulated adrenocorticotropic hormone secretion in a patient with pituitary hyperplasia due to primary hypothyroidism.

    PubMed

    Ban, Y; Ban, Y; Taniyama, M; Hara, H; Abe, T; Katagiri, T

    2000-08-01

    We report a patient with primary hypothyroidism associated with an aberrant ACTH response to the LH-RH test. A 40-year-old woman was admitted to our hospital displaying headache, nausea, and numbness on the left side of her face, upper limbs, and tips of her toes. Computed tomography and magnetic resonance imaging revealed a mass-like lesion in the pituitary. A high serum TSH concentration with concomitant low thyroid hormone concentrations resulted in a diagnosis of primary hypothyroidism. To exclude the possibility of a coexisting pituitary tumor including a TSH-secreting tumor, we performed dynamic TSH secretion tests. TRH testing showed an excessive, delayed TSH response, typical of primary hypothyroidism. Serum TSH decreased not only after administration of CRH, octreotide, or L-DOPA, but also after administration of LH-RH. In this case, LH-RH testing induced ACTH secretion. To determine if aberrant ACTH secretion in response to LH-RH loading is a common phenomenon in severe primary hypothyroidism, we performed the LH-RH test on 4 additional patients with pituitary enlargement due to primary hypothyroidism. Two patients demonstrated aberrant ACTH secretion in response to LH-RH loading, but the others did not. To our knowledge, this is the first report of aberrant LH-RH-stimulated ACTH secretion in primary hypothyroidism.

  11. Fuel oil-induced adrenal hypertrophy in ranch mink (Mustela vison): effects of sex, fuel oil weathering, and response to adrenocorticotropic hormone.

    PubMed

    Mohr, F C; Lasley, B; Bursian, S

    2010-01-01

    Environmental contamination by petroleum hydrocarbons from anthropogenic sources can be a cause of stress for free-ranging wildlife. The response of wildlife to chemical contaminants requires that the hypothalamic-pituitary-adrenal (HPA) axis be precisely regulated to allow for proper glucocorticoid-mediated adaptive responses. Chronic oral exposure to low concentrations of bunker C fuel oil causes the development of adrenal hypertrophy in male ranch mink (Mustela vison) without increasing serum or fecal glucocorticoid concentrations. This hypertrophy is an adaptive response to fuel oil-induced adrenal insufficiency. To determine if the same phenomenon occurs in female mink or male mink exposed to artificially weathered fuel oil, female mink were fed 0 ppm (mineral oil) or 420 ppm fuel oil and male mink were exposed to 0 ppm, 420 ppm fuel oil, or 480 ppm artificially weathered fuel oil in the diet for 60-62 days. At the end of the exposure, serum glucocorticoid concentrations were assayed along with body and organ weight measurements. Fecal glucocorticoid concentrations were assayed at time points throughout the exposure. Male mink fed fuel oil or weathered fuel oil and female mink fed fuel oil had adrenal enlargement without any significant increases in the serum or fecal concentration of glucocorticoids, which is consistent with fuel oil-induced adrenal insufficiency. To address the physiological consequences of adrenal insufficiency, fuel oil-exposed male mink were administered an adrenocorticotropic hormone (ACTH) stimulation test. Fuel oil-exposed animals had a smaller incremental increase in serum glucocorticoid concentration after ACTH challenge compared to control animals. Our findings provide further evidence that the HPA axis of fuel oil-exposed animals is compromised and, therefore, not able to respond appropriately to the diverse stressors found in the environment.

  12. Adrenocorticotropic hormone protects learning and memory function in epileptic Kcna1-null mice.

    PubMed

    Scantlebury, Morris H; Chun, Kyoung-Chul; Ma, Shun-Chieh; Rho, Jong M; Kim, Do Young

    2017-04-03

    ACTH, a member of the melanocortin family of peptides, is often used in the treatment of the developmental epileptic encephalopathy spectrum disorders including, Ohtahara, West, Lennox Gastaut and Landau-Kleffner Syndromes and electrical status epilepticus of sleep. In these disorders, although ACTH is often successful in controlling the seizures and/or inter-ictal EEG abnormalities, it is unknown whether ACTH possesses other beneficial effects independent of seizure control. We tested whether ACTH can ameliorate the intrinsic impairment of hippocampal-based learning and memory in epileptic Kcna1-null (KO) mice. We found that ACTH - administered in the form of Acthar Gel given i.p. four times daily at a dose of 4 IU/kg (16 IU/kg/day) for 7days - prevented impairment of long-term potentiation (LTP) evoked with high-frequency stimulation in CA1 hippocampus and also restored spatial learning and memory on the Barnes maze test. However, with this treatment regimen, ACTH did not exert a significant effect on the frequency of spontaneous recurrent seizures. Together, our findings indicate that ACTH can ameliorate memory impairment in epileptic Kcna1-null mice separate from seizure control, and suggest that this widely used peptide may exert direct nootropic effects in the epileptic brain.

  13. Effects of adrenocorticotropic hormone and flunixin meglumine on pregnancy retention in beef cows.

    PubMed

    Geary, T W

    2012-01-01

    Pregnancy loss in beef cattle after d 28 of gestation is variable, but it has been reported to be as great as 14% and has been related to transportation or handling stress. The primary objective of this study was to determine whether activation of the hypophyseal-adrenal axis with ACTH would mimic a stressful response and cause pregnancy loss in beef cattle. A secondary objective was to determine if a single injection of the PG synthesis inhibitor flunixin meglumine would attenuate the stress response and suppress serum PGF(2α) concentrations to prevent pregnancy loss. Forty nonlactating beef cows that were 34 ± 0.33 d pregnant were used for this study. In a 2 × 3 factorial arrangement, cows were randomly assigned to receive ACTH [0 or 0.5 IU/kg of BW, intramuscularly (i.m.)] at 0 and 2 h of the study and flunixin meglumine (0, 1.1, or 2.2 mg/kg of BW, i.m.) at 0 h. Blood samples were collected from all cows at 0 h and every 30 min for 4 h to measure serum cortisol and PGF(2α) metabolite (PGFM) concentrations. Rectal temperature was collected for each cow at 0, 120, and 240 min. Pregnancy exams were conducted 31 and 58 d after treatment by transrectal ultrasonography, and the presence of a fetal heartbeat was used as an indicator of fetal viability. Serum cortisol concentration was affected (P < 0.01) by ACTH, time, and the interaction of ACTH × time, but not by flunixin meglumine (P ≥ 0.14) or any other interactions. Cortisol concentrations increased (P < 0.01) in the serum of ACTH-treated cows immediately after ACTH treatment and remained increased (P < 0.01) throughout the 4-h sampling period. Serum PGFM concentration was not affected by ACTH (P = 0.97) or by any interactions (P > 0.35) with ACTH, but was affected (P < 0.01) by flunixin meglumine, time, and the interaction of flunixin meglumine × time. Regardless of dosage (1.1 or 2.2 mg/kg of BW), flunixin meglumine decreased (P < 0.01) serum PGFM concentrations in both ACTH-treated and control cows for

  14. Stress Hormones and their Regulation in a Captive Dolphin Population

    DTIC Science & Technology

    2013-09-30

    stimulation experiments, an animal’s hormonal and physiological response to a simulated stressor can be evaluated. Adrenocorticotropic hormone (ACTH) is...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Stress Hormones and Their Regulation in a Captive...will determine baseline levels of putative stress hormones and evaluate the functional consequences of increased stress in the bottlenose dolphin

  15. Treatable Bedridden Elderly―Recovery from Flexion Contracture after Cortisol Replacement in a Patient with Isolated Adrenocorticotropic Hormone Deficiency

    PubMed Central

    Tanaka, Takamasa; Terada, Norihiko; Fujikawa, Yoshiki; Fujimoto, Takushi

    2016-01-01

    Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder with diverse clinical presentations. A 79-year-old man was bedridden for six months due to flexion contractures of the bilateral hips and knees, along with hyponatremia. He was diagnosed with IAD based on the results of endocrine tests. After one month of corticosteroid replacement, he recovered and was able to stand up by himself. Although flexion contracture is a rare symptom of IAD, steroid replacement therapy may be effective, even for seemingly irreversibly bedridden elderly patients. In bedridden elderly patients with flexion contractures, we should consider and look for any signs of adrenal insufficiency. PMID:27746435

  16. Treatable Bedridden Elderly -Recovery from Flexion Contracture after Cortisol Replacement in a Patient with Isolated Adrenocorticotropic Hormone Deficiency.

    PubMed

    Tanaka, Takamasa; Terada, Norihiko; Fujikawa, Yoshiki; Fujimoto, Takushi

    Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder with diverse clinical presentations. A 79-year-old man was bedridden for six months due to flexion contractures of the bilateral hips and knees, along with hyponatremia. He was diagnosed with IAD based on the results of endocrine tests. After one month of corticosteroid replacement, he recovered and was able to stand up by himself. Although flexion contracture is a rare symptom of IAD, steroid replacement therapy may be effective, even for seemingly irreversibly bedridden elderly patients. In bedridden elderly patients with flexion contractures, we should consider and look for any signs of adrenal insufficiency.

  17. Effects of adrenocorticotropic hormone and flunixin meglumine on pregnancy retention in beef cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pregnancy loss in beef cattle after d 28 of gestation is variable, but has been reported to be as high as 14% and has been related to transportation or handling stress. The objective of this study was to determine effects of ACTH administration on mimicking a stress response and whether this respon...

  18. Concentrations of the adrenocorticotropic hormone, corticosterone and sex steroid hormones and the expression of the androgen receptor in the pituitary and adrenal glands of male turkeys (Meleagris gallopavo) during growth and development.

    PubMed

    Kiezun, J; Kaminska, B; Jankowski, J; Dusza, L

    2015-01-01

    Androgens take part in the regulation of puberty and promote growth and development. They play their biological role by binding to a specific androgen receptor (AR). The aim of this study was to evaluate the expression of AR mRNA and protein in the pituitary and adrenal glands, to localize AR protein in luteinizing hormone (LH)-producing pituitary and adrenocortical cells, to determine plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone and the concentrations of corticosterone, testosterone (T), androstenedione (A4) and oestradiol (E2) in the adrenal glands of male turkeys at the age of 4, 8, 12, 16, 20, 24 and 28weeks. The concentrations of hormones and the expression of AR varied during development. The expression of AR mRNA and protein in pituitary increased during the growth. The increase of AR mRNA levels in pituitary occurred earlier than increase of AR protein. The percentage of pituitary cells expressing ARs in the population of LH-secreting cells increased in week 20. It suggests that AR expression in LH-producing pituitary cells is determined by the phase of development. The drop in adrenal AR mRNA and protein expression was accompanied by an increase in the concentrations of adrenal androgens. Those results could point to the presence of a compensatory mechanism that enables turkeys to avoid the potentially detrimental effects of high androgen concentrations. Our results will expand our knowledge of the role of steroids in the development of the reproductive system of turkeys from the first month of age until maturity.

  19. The effect of intracarotid vasopressin infusion on ACTH release in neurohypophysectomized, conscious dogs.

    PubMed

    Raff, H; Papanek, P E; Liard, J F; Cowley, A W

    1994-09-01

    Neurohypophysectomy (NHX) attenuates the adrenocorticotropic hormone (ACTH) response to arterial hypotension but not corticotropin-releasing hormone (CRH) or insulin-induced hypoglycemia in conscious dogs. The purpose of the present study was to determine if increasing vasopressin (AVP) in the cephalic circulation by carotid infusion normalizes the ACTH response to hypotension attenuated by NHX. Five male, conditioned dogs underwent controlled, acute decreases in arterial pressure (by approximately 25 mmHg) by infusion of sodium nitroprusside (NP) before and > 4 wk after selective NHX. ACTH increased from 40 +/- 3 to 242 +/- 79 pg/ml during NP in the intact state. This response was greatly attenuated after NHX (peak ACTH 81 +/- 15 pg/ml). Simultaneous intravenous infusion of AVP (12.5 ng/min) had a small, augmenting effect on the ACTH response to NP (peak ACTH 120 +/- 27 pg/ml). Intracarotid AVP (12.5 ng/min) greatly augmented the ACTH response to NP (peak ACTH 202 +/- 26 pg/ml) such that it was no longer different from the intact response. Neither intravenous nor intracarotid AVP infusion per se had a great effect on ACTH. A normal ACTH response to hypotension requires an intact neurohypophysis and is mediated by a cephalic action of magnocellular AVP.

  20. Variability of Hormonal Stress Markers and Stress Responses in a Large Cross-Sectional Sample of Elephant Seals

    DTIC Science & Technology

    2012-09-30

    adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH) challenges and characterize the activation of the hypothalamic-pituitary-adrenal...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Variability of Hormonal Stress Markers and Stress...number. 1. REPORT DATE 2012 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Variability of Hormonal Stress Markers and Stress

  1. alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells.

    PubMed

    Elliott, Richard J; Szabo, Marika; Wagner, Mark J; Kemp, E Helen; MacNeil, Sheila; Haycock, John W

    2004-04-01

    alpha-MSH signals by binding to the melanocortin-1 receptor (MC-1R) and elevating cyclic AMP in several different cells. The anti-inflammatory properties of this peptide are also believed to be cyclic AMP dependent. The carboxyl terminal tripeptides of alpha-MSH (KPV / KP-D-V) are the smallest minimal sequences reported to prevent inflammation but it is not known if they operate via MC-1R or cyclic AMP. The aim of this study was to examine the intracellular signalling of key MSH and ACTH peptides in human keratinotocytes. No elevation in cyclic AMP was detected in either HaCaT or normal human keratinocytes in response to alpha-MSH, KPV or ACTH peptides. Rapid and acute intracellular calcium, however, were observed in HaCaT keratinocytes in response to alpha-MSH (10(-15)-10(-7) M), KPV (10(-15)-10(-7) M), KP-D-V (10(-15)-10(-7) M) and ACTH (10(-15)-10(-7) M), but only in the presence of PIA, an adenosine agonist that inhibits the cyclic AMP pathway. Normal keratinocytes responded to all the above peptides but in addition responded to ACTH 1-17 (10(-13)-10(-7) M) in contrast to the HaCaT keratinocytes. Stable transfection of Chinese hamster ovary cells with the MC-1 receptor showed that alpha-MSH and the KPV peptides elevated intracellular calcium.

  2. Single-Session CT-Guided Percutaneous Microwave Ablation of Bilateral Adrenal Gland Hyperplasia Due to Ectopic ACTH Syndrome

    SciTech Connect

    Sarma, Asha Shyn, Paul B.; Vivian, Mark A.; Ng, Ju-Mei; Tuncali, Kemal; Lorch, Jorchen H.; Zaheer, Sarah N.; Gordon, Michael S.; Silverman, Stuart G.

    2015-10-15

    Bilateral adrenalectomy is currently the only available treatment for adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (ectopic ACTH syndrome) that is refractory to pharmacologic therapy. We describe two patients with refractory ectopic ACTH syndrome who were treated with CT-guided percutaneous microwave ablation of both hyperplastic adrenal glands in a single session: One was not a surgical candidate, and the other had undergone unsuccessful surgery. Following the procedure, both patients achieved substantial decreases in serum cortisol, symptomatic improvement, and decreased anti-hypertensive medication requirements.

  3. ATRAZINE DOES NOT INDUCE GASTROINTESTINAL DISCOMFORT (PICA) IN RATS AT DOSES THAT INCREASE ACTH ANDCORTICOSTERONE RELEASE AND CAUSE CONDITIONED TASTE AVERSION.

    EPA Science Inventory

    Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH) and serum corticosterone (CORT), with a LOEL of 12.5mg/kg. The mechanism for these effects is unk...

  4. Apelin is involved in postprandial responses and stimulates secretion of arginine-vasopressin, adrenocorticotropic hormone, and growth hormone in the ruminant.

    PubMed

    Sato, K; Takahashi, T; Kobayashi, Y; Hagino, A; Roh, S G; Katoh, K

    2012-04-01

    Apelin and its mRNA are expressed in several tissues, including the supraoptic and paraventricular nuclei in the hypothalamus. Although apelin is reported to be involved in the regulation of fluid homeostasis, little is known about the postprandial dynamics of apelin in plasma and its regulatory effects on the anterior pituitary hormones of ruminants. Therefore, the aims of this study were to investigate the following: (1) changes in plasma apelin concentrations in response to food intake under conditions of hydration (free access to water) or dehydration (water restriction), and (2) the effects of intravenous administration of apelin on plasma concentrations of arginine-vasopressin (AVP), ACTH, GH, and insulin. In Experiment 1 with the use of goats, the postprandial plasma apelin concentration was significantly increased under the dehydration condition compared with the hydration condition, and this increase was accompanied by increased plasma concentrations of AVP and ACTH after 24 h of dehydration. In Experiment 2 with the use of sheep and hydration conditions, the intravenous administration of apelin ([Pyr(1)]-apelin-13; 0.5 mg/head) caused a tendency to increase or caused a significant increase in plasma concentrations of AVP, ACTH, GH, insulin, and glucose. On the basis of these findings, we concluded that apelin is involved in the feeding process, and it regulates endocrine functions in the anterior pituitary gland via AVP in ruminant animals.

  5. Ectopic adrenocorticotropic hormone syndrome caused by neuroendocrine tumors of the thymus: 30-year experience with 16 patients at a single institute in the People’s Republic of China

    PubMed Central

    Chen, Ye-ye; Li, Shan-qing; Liu, Hong-sheng; Qin, Ying-zhi; Li, Li; Huang, Cheng; Bi, Ya-lan; Meng, Yun-xiao; He, Jia; Zhou, Xiao-yun; Ma, Dong-jie

    2016-01-01

    Background and purpose Thymic neuroendocrine carcinomas (TNECs) are extremely uncommon. Certain cases of TNECs can produce the adrenocorticotropic hormone (ACTH) and cause ectopic ACTH syndrome (EAS). The current literature on this topic consists mainly of case reports, and therapeutic guidelines are lacking. The aim of this study was to discuss the diagnosis, surgical management, and prognosis of EAS caused by TNECs to improve clinical experience with this rare disease. Methods From June 1984 to June 2014, at the Peking Union Medical College Hospital, the surgical interventions and follow-up outcomes of 16 consecutive patients (eight men and eight women) with EAS caused by TNECs were retrospectively analyzed. Results The median age was 32.5 years (range: 13–47 years), and the median disease duration was 8.5 months (range: 1–150 months). All patients presented with clinical and biochemical evidence indicating a diagnosis of Cushing’s syndrome. Contrast-enhanced thoracic computed tomography scans were critical to locating the ACTH-producing tumor and evaluating the feasibility of resection. All patients underwent surgery. One patient died of septicemia in the intensive care unit 2 weeks after surgery. No other morbidity or mortality occurred during the perioperative period. The median overall survival (OS) was 41 months (95% CI: 30.3–51.7 months), and the progression-free survival was 28 months (95% CI: 21.6–34.3 months). Both overall survival (P=0.002) and progression-free survival (P=0.030) improved significantly after complete resection. Conclusion TNEC is an extremely aggressive disease that should be considered when treating patients with Cushing’s syndrome due to ectopic ACTH secretion. In particular, all suspected patients should undergo contrast-enhanced thoracic computed tomography scans to facilitate early diagnosis. The current first-line treatment is surgical resection, and complete resection is a favorable prognostic factor. However

  6. Severe hyponatremia due to ACTH insufficiency in a 14 year-old girl with growth hormone deficiency.

    PubMed

    Tseng, Lo-Lin; Lue, Hung-Chi; Huang, Cheng-Hung; Niu, Dau-Ming

    2010-01-01

    SIADH-like hyponatremia as the presenting manifestation of ACTH deficiency is rare in childhood. Here we report a 14 year-old girl who, after 8 years of GH replacement and subsequent treatment for subclinical secondary hypothyroidism, presented with confusion and disorientation due to severe hyponatremia. When her pituitary axis was re-assessed, she was diagnosed as having ACTH deficiency associated with multiple pituitary hormone deficiencies (MPHD) (including GH, FSH, LH, and subclinical TSH deficiencies). She responded poorly to treatment with only hypertonic fluid, but improved after addition of hydrocortisone replacement. The purpose of this paper is to emphasize the importance of suspecting ACTH insufficiency in children with GH deficiency if hyponatremia develops.

  7. [West syndrome: clinical and electroencephalographic follow up of 70 patients and response to its treatment with adrenocorticotropic hormone, prednisone, vigabatrin, nitrazepam and valproate].

    PubMed

    Antoniuk, S A; Bruck, I; Spessatto, A; Halick, S M; de Bruyn, L R; Meister, E; de Paola, D

    2000-09-01

    In a retrospective study we assessed the outcome of the criptogenic and symptomatic forms of West syndrome and evaluated the efficacy of adrenocorticotropic hormone, vigabatrin, prednisone, valproate and nitrazepam in the spasms control. Seventy patients were follwed up by 2 years. Twelve (17%) were criptogenics and 58 (83%) symptomatics. In criptogenic group significantly more patients were in regular school classes and with normal motor development, better control of seizure, less tendency to evoluate to Lennox Gastaut syndrome and 83. 3% had control of spasms (72.4% of patients from symptomatic group had control of spasms). Adrenocorticotropic hormone and vigabatrin were the most efective drugs, with 68.75% and 60% of spasms control, respectivelly, when used as first line of therapy and 75% and 50%, respectivelly, as second line of therapy.

  8. Levels of central oxytocin and glucocorticoid receptor and serum adrenocorticotropic hormone and corticosterone in mandarin voles with different levels of sociability.

    PubMed

    Qiao, Xufeng; Yan, Yating; Tai, Fadao; Wu, Ruiyong; Hao, Ping; Fang, Qianqian; Zhang, Shuwei

    2014-11-01

    Sociability is the prerequisite to social living. Oxytocin and the hypothalamo-pituitary-adrenocortical axis mediate various social behaviors across different social contexts in different rodents. We hypothesized that they also mediate levels of non-reproductive social behavior. Here we explored naturally occurring variation in sociability through a social preference test and compared central oxytocin, glucocorticoid receptors, serum adrenocorticotropic hormone and corticosterone in mandarin voles with different levels of sociability. We found that low-social voles showed higher levels of anxiety-like behavior in open field tests, and had more serum adrenocorticotropic hormone and corticosterone than high-social voles. High-social individuals had more glucocorticoid receptor positive neurons in the hippocampus and more oxytocin positive neurons in the paraventricular nuclei and supraoptic nuclei of the hypothalamus than low-social individuals. Within the same level of sociability, females had more oxytocin positive neurons in the paraventricular nuclei and supraoptic nuclei of the hypothalamus than males. These results indicate that naturally occurring social preferences are associated with higher levels of central oxytocin and hippocampus glucocorticoid receptor and lower levels of anxiety and serum adrenocorticotropic hormone and corticosterone.

  9. Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analog.

    PubMed

    Shadrina, M I; Dolotov, O V; Grivennikov, I A; Slominsky, P A; Andreeva, L A; Inozemtseva, L S; Limborska, S A; Myasoedov, N F

    2001-08-03

    The proliferation, differentiation and survival of neuronal and glial cells are affected by a number of neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and others. In a previous study, we observed the effects of 'Semax' (Met-Glu-His-Phe-Pro-Gly-Pro), the physiologically active analogue of adrenocorticotropic hormone(4--10), on neuronal cell survival in vitro. We hypothesized that these effects may be mediated by the regulation of expression of some neurotrophic factors. To test this hypothesis we analyzed NGF and BDNF gene expression in glial cells obtained from the basal forebrain of newborn rats, following in vitro treatment with 'Semax'. We observed changes in mRNA levels for both the NGF and BDNF genes. The greatest increase in expression was found after 30 min of 'Semax' administration. At this time, BDNF mRNA level was increased eight-fold in comparison with control, and NGF mRNA level was increased five-fold.

  10. Effect of hypotension and hyperosmolality on vasopressin and ACTH responses to hypoglycemia in conscious dogs.

    PubMed

    Raff, H; Papanek, P E; Cowley, A W

    1992-08-01

    The purpose of these studies was, first, to determine whether hypertonic saline (HS) infusion or nitroprusside (NiPr)-induced hypotension augments the vasopressin (AVP) and adrenocorticotropic hormone (ACTH) responses to insulin (Ins)-induced hypoglycemia and, second, to determine whether neurohypophysectomy could attenuate the augmentation. Conscious, male dogs (n = 8) underwent two different types of experiments. In the first, Ins was preceded by either a 30-min infusion of normal saline (control) or HS to raise plasma osmolality and AVP. HS augmented the AVP response but diminished the ACTH response to Ins. In the second group of experiments, Ins was preceded by a controlled decrease in mean arterial pressure using NiPr, which led to an increase in AVP and ACTH. The initial ACTH and AVP response to Ins was augmented by NiPr, but this early augmentation was not sustained. Neurohypophysectomy attenuated the early augmentation of the ACTH response to Ins by NiPr, but did not alter the final ACTH level achieved. We conclude that HS augmented the AVP but inhibited the ACTH response to Ins probably because of expansion of plasma volume. Concomitant hypotension led to an augmentation of the early but not sustained AVP and ACTH response to Ins. Neurohypophysectomy eliminated this augmentation, suggesting a role for AVP from the neural lobe in the early ACTH response to combined hypotension and Ins-induced hypoglycemia.

  11. Medullary nephrocalcinosis and pancreatic calcifications demonstrated by ultrasound and CT in infants after treatment with ACTH

    SciTech Connect

    Rausch, H.P.; Hanefield, F.; Kaufmann, B.J.

    1984-10-01

    Thirteen patients who had undergone prolonged adrenocorticotropic hormone (ACTH) therapy for infantile spasms or encephalopathy were examined with sonography. Nine patients were seen to have appearances characteristic of medullary nephrocalcinosis. Five patients also showed a homogeneously increased echogenicity of the whole pancreas on sonography, and one of these showed increased density on computed tomography. Density measurements were in the range of calcific arterial within the papillae and pancreatic tissue. On abdominal survey radiographs, even in retrospect, no calcifications could be recognized.

  12. Concurrent papillary thyroid cancer with pituitary ACTH-secreting tumor.

    PubMed

    Kuo, Sheng-Fong; Chen, Jeng-Yeou; Chuang, Wen-Yu; Jung, Shih-Ming; Chang, Yu-Chen; Lin, Jen-Der

    2007-04-01

    Concomitant thyroid cancer with pituitary tumor is uncommon. This study reports a case of advanced papillary thyroid carcinoma with pituitary adrenocorticotropic hormone (ACTH)-secreting tumor. A 58-year-old male patient had thyroid cancer in 1991 and presented with headache caused by pituitary tumor with apoplexy in 1993. Due to hypopituitarism, the patient underwent radioactive iodide ((131)I) for detection and treatment of metastatic thyroid cancer after the use of recombinant human thyroid-stimulating hormone (rhTSH) in 2000. During follow-up for thyroid cancer, (201)thallium scan proved to be an effective tool for detecting metastatic thyroid cancer in the patient without pituitary TSH reserve. Pituitary ACTH-secreting tumor was confirmed in 2001 based on the high serum ACTH level and positive immunohistochemical stain for ACTH. The patient had no Cushingoid features. Moreover, serum ACTH levels were 337 and 232 pg/mL with normal serum cortisol and urine-free cortisol. Although the patient underwent three operations and a total of 370 mCi (131)I therapy for recurrent thyroid cancer, the cancer continued to progress. Finally, the patient died of pneumonia with septic shock 12 years after the diagnosis of thyroid cancer.

  13. Secretory pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic-releasing hormones.

    PubMed

    Riedel, W; Layka, H; Neeck, G

    1998-01-01

    To study the hormonal perturbations in FMS patients we injected sixteen FMS patients and seventeen controls a cocktail of the hypothalamic releasing hormones: Corticotropin-releasing hormone (CRH), Thyrotropin-releasing hormone (TRH), Growth hormone-releasing hormone (GHRH), and Luteinizing hormone-releasing hormone (LHRH) and observed the hormonal secretion pattern of the pituitary together with the hormones of the peripheral endocrine glands. We found in FMS patients elevated basal values of ACTH and cortisol, lowered basal values of insulin-like growth factor I (IGF-I) and of triiodothyronine (T3), elevated basal values of follicle-stimulating hormone (FSH) and lowered basal values of estrogen. Following injection of the four releasing-hormones, we found in FMS patients an augmented response of ACTH, a blunted response of TSH, while the prolactin response was exaggerated. The effects of LHRH stimulation were investigated in six FMS patients and six controls and disclosed a significantly blunted response of LH in FMS. We explain the deviations of hormonal secretion in FMS patients as being caused by chronic stress, which, after being perceived and processed by the central nervous system (CNS), activates hypothalamic CRH neurons. CRH, on the one hand, activates the pituitary-adrenal axis, but also stimulates at the hypothalamic level somatostatin secretion which, in turn, causes inhibition of GH and TSH at the pituitary level. The suppression of gonadal function may also be attributed to elevated CRH by its ability to inhibit hypothalamic LHRH release, although it could act also directly on the ovary by inhibiting FSH-stimulated estrogen production. We conclude that the observed pattern of hormonal deviations in FMS patients is a CNS adjustment to chronic pain and stress, constitutes a specific entity of FMS, and is primarily evoked by activated CRH neurons.

  14. Can ACTH therapy improve the long-term outcome of drug-resistant frontal lobe epilepsy?

    PubMed

    Gobbi, Giuseppe; Loiacono, Giulia; Boni, Antonella; Marangio, Lucia; Verrotti, Alberto

    2014-06-01

    Frontal lobe epilepsy is a common focal epilepsy in children and is often difficult to treat. Adrenocorticotropic hormone (ACTH) or steroids have been used for patients with several forms of medically intractable epilepsy. We evaluated the short, medium, and long-term evolution of patients with frontal lobe epilepsy and secondary bilateral synchrony on the EEG, who received ACTH treatment. Patients were recruited for an add-on trial during clinical practice, and data was retrospectively analysed. The study group comprised 6 patients treated with ACTH. The effects of ACTH were assessed in the short term (at the end of a 6-week period of ACTH treatment), medium term (at 6 months after the end of treatment), and long term (at 12 months after the end of treatment). At short-term follow-up, ACTH treatment was effective for all types of seizures in 5 of 6 patients and ineffective in 1 patient. All patients who were seizure-free at the end of ACTH treatment maintained an excellent outcome, remaining seizure-free at the end of follow-up. Our study demonstrates that ACTH may represent an effective treatment for frontal lobe epilepsy with secondary bilateral synchrony. Further double-blind prospective studies are required to confirm our initial findings.

  15. Reciprocal regulation of a glucocorticoid receptor-steroidogenic factor-1 transcription complex on the Dax-1 promoter by glucocorticoids and adrenocorticotropic hormone in the adrenal cortex.

    PubMed

    Gummow, Brian M; Scheys, Joshua O; Cancelli, Victoria R; Hammer, Gary D

    2006-11-01

    Numerous genes required for adrenocortical steroidogenesis are activated by the nuclear hormone receptor steroidogenic factor 1 (SF-1) (NR5A1). Dax-1 (NR0B1), another nuclear hormone receptor, represses SF-1-dependent activation. Glucocorticoid products of the adrenal cortex provide negative feedback to the production of hypothalamic CRH and pituitary ACTH. We hypothesized that glucocorticoids stimulate an intraadrenal negative feedback loop via activation of Dax-1 expression. Reporter constructs show glucocorticoid-dependent synergy between SF-1 and glucocorticoid receptor (GR) in the activation of Dax-1, which is antagonized by ACTH signaling. We map the functional glucocorticoid response element between -718 and -704 bp, required for activation by GR and synergy with SF-1. Of three SF-1 response elements, only the -128-bp SF-1 response element is required for synergy with GR. Chromatin immunoprecipitation (ChIP) assays demonstrate that dexamethasone treatment increases GR and SF-1 binding to the endogenous murine Dax-1 promoter 10- and 3.5-fold over baseline. Serial ChIP assays reveal that that GR and SF-1 are part of the same complex on the Dax-1 promoter, whereas coimmunoprecipitation assay confirms the presence of a protein complex that contains both GR and SF-1. ACTH stimulation disrupts the formation of this complex by abrogating SF-1 binding to the Dax-1 promoter, while promoting SF-1 binding to the melanocortin-2 receptor (Mc2r) and steroidogenic acute regulatory protein (StAR) promoters. Finally, dexamethasone treatment increases endogenous Dax-1 expression and concordantly decreases StAR expression. ACTH signaling antagonizes the increase in Dax-1 yet strongly activates StAR transcription. These data indicate that GR provides feedback regulation of adrenocortical steroid production through synergistic activation of Dax-1 with SF-1, which is antagonized by ACTH activation of the adrenal cortex.

  16. Omnigen-AF reduces basal plasma cortisol, AWA cortisol release to adrencocorticotropic hormone or corticotrophin releasing hormone & vasopressin in lactating dairy cows under thermoneutral or acute heat stress conditions.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Differences in the adrenal cortisol response of OmniGen-AF (OG) supplemented dairy cows to a corticotrophin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 1...

  17. Efficacy of single serum cortisol reading obtained between 9 AM and 10 AM as an index of adrenal function in children treated with glucocorticoids or synthetic adrenocorticotropic hormone.

    PubMed

    Goto, Masahiro; Shibata, Nao; Hasegawa, Yukihiro

    2016-07-01

    To find a simple method to screen for iatrogenic childhood adrenal insufficiency, we retrospectively examined the results of CRH stimulation tests performed 212 times on 111 subjects (68 males; age at commencement of initial treatment ranged 0.0-19.8 yr; median age, 5.8 yr). Before the commencement of this study, 97 subjects had been treated with glucocorticoids and 14 subjects with West syndrome had been treated with synthetic adrenocorticotropic hormone. Duration of the primary treatment ranged from 15 to 2150 days. CRH stimulation tests were conducted between 09:00 AM and 10:00 AM and peak cortisol values less than 15 µg/dL were considered indicative of adrenal insufficiency. The receiver operating characteristic curve showed that the optimal basal serum cortisol cut-off values when screening for adrenal suppression ranged from 5.35 to 5.80 µg/dL depending on the primary disease. All subjects having a serum cortisol value of less than 2.3 µg/dL had insufficient adrenal function while all subjects having greater than 11 µg/dL had intact adrenal function. We concluded that single serum cortisol values obtained between 09:00 AM and 10:00 AM had the potential to serve as an index of adrenal function in children treated with glucocorticoids or synthetic adrenocorticotropic hormone.

  18. Hypokalaemia: common but not always benign. Severe, persistent hypokalaemia secondary to ectopic ACTH from a carcinoid tumour.

    PubMed

    Mahmood, Muhammad Muzaffar; John, Kurien

    2012-11-14

    Hypokalaemia is a common and often benign observation. There is usually an obvious underlying cause for the anomaly. However, hypokalaemia can very rarely be the sole presentation of a more sinister disease. A high index of suspicion and a systematic approach are therefore required to avoid delays in the management, especially in the context of presentation to a medical team. We present a case of a patient with severe and persistent hypokalaemia due to ectopic adrenocorticotropic hormone (ACTH) secretion secondary to a carcinoid tumour. The case report is followed by a brief discussion on the approach to the management of hypokalaemia and additional tests to confirm ectopic ACTH.

  19. Impact of ACTH Signaling on Transcriptional Regulation of Steroidogenic Genes

    PubMed Central

    Ruggiero, Carmen; Lalli, Enzo

    2016-01-01

    The trophic peptide hormone adrenocorticotropic (ACTH) stimulates steroid hormone biosynthesis evoking both a rapid, acute response and a long-term, chronic response, via the activation of cAMP/protein kinase A (PKA) signaling. The acute response is initiated by the mobilization of cholesterol from lipid stores and its delivery to the inner mitochondrial membrane, a process that is mediated by the steroidogenic acute regulatory protein. The chronic response results in the increased coordinated transcription of genes encoding steroidogenic enzymes. ACTH binding to its cognate receptor, melanocortin 2 receptor (MC2R), stimulates adenylyl cyclase, thus inducing cAMP production, PKA activation, and phosphorylation of specific nuclear factors, which bind to target promoters and facilitate coactivator protein recruitment to direct steroidogenic gene transcription. This review provides a general view of the transcriptional control exerted by the ACTH/cAMP system on the expression of genes encoding for steroidogenic enzymes in the adrenal cortex. Special emphasis will be given to the transcription factors required to mediate ACTH-dependent transcription of steroidogenic genes. PMID:27065945

  20. ACTH Modulates PTP-PEST Activity and Promotes Its Interaction With Paxillin.

    PubMed

    Gorostizaga, Alejandra Beatriz; Mori Sequeiros Garcia, M Mercedes; Acquier, Andrea B; Lopez-Costa, Juan J; Mendez, Carlos F; Maloberti, Paula M; Paz, Cristina

    2016-09-01

    Adrenocorticotropic hormone (ACTH) treatment has been proven to promote paxillin dephosphorylation and increase soluble protein tyrosine phosphatase (PTP) activity in rat adrenal zona fasciculata (ZF). Also, in-gel PTP assays have shown the activation of a 115-kDa PTP (PTP115) by ACTH. In this context, the current work presents evidence that PTP115 is PTP-PEST, a PTP that recognizes paxillin as substrate. PTP115 was partially purified from rat adrenal ZF and PTP-PEST was detected through Western blot in bioactive samples taken in each purification step. Immunohistochemical and RT-PCR studies revealed PTP-PEST expression in rat ZF and Y1 adrenocortical cells. Moreover, a PTP-PEST siRNA decreased the expression of this phosphatase. PKA phosphorylation of purified PTP115 isolated from non-ACTH-treated rats increased KM and VM . Finally, in-gel PTP assays of immunoprecipitated paxillin from control and ACTH-treated rats suggested a hormone-mediated increase in paxillin-PTP115 interaction, while PTP-PEST and paxillin co-localize in Y1 cells. Taken together, these data demonstrate PTP-PEST expression in adrenal ZF and its regulation by ACTH/PKA and also suggest an ACTH-induced PTP-PEST-paxillin interaction. J. Cell. Biochem. 117: 2170-2181, 2016. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals, Inc.

  1. Ectopic ACTH secretion due to a bronchopulmonary carcinoid localized by somatostatin receptor scintigraphy.

    PubMed

    Iser, G; Pfohl, M; Dörr, U; Weiss, E M; Seif, F J

    1994-11-01

    We present the case of a 65-year-old woman with an adrenocorticotropic hormone (ACTH) secreting bronchopulmonary carcinoid. This patient showed the typical long history of Cushing's syndrome, including hypokaliemia, impaired glucose tolerance, high levels of ACTH and beta-endorphin, and coproduction of other peptides. At the onset of clinical symptoms in 1979 an adrenal adenoma was suspected, and left-sided adrenalectomy was performed. The symptoms soon recurred, and the diagnosis of ACTH-dependent Cushing's syndrome was made. As no ACTH-secreting tumor was found, the right adrenal was resected, and the patient was followed up regularly. Fourteen years later chest roentgenography and computed tomography revealed a para-aortic pulmonary lesion, which was suspicious for a bronchopulmonary carcinoid. ACTH and beta-endorphin were excessively, pancreatic polypeptide slightly elevated at that time. The final diagnosis was made using somatostatin receptor scintigraphy which confirmed the hormonal activity of the suspicious lesion; no additional focus was found. This method turned out to be not only a useful additional localization technique but also a promising tool for characterization and staging of a suspected ACTH-producing carcinoid. The tumor was resected curatively, and the diagnosis was confirmed histologically.

  2. Stress Hormone Changes and Marital Conflict: Spouses Relative Power Makes a Difference

    ERIC Educational Resources Information Center

    Loving, Timothy J.; Heffner, Kathi L.; Kiecoltglaser, Janice K.; Glaser, Ronald; Malarkey, William B.

    2004-01-01

    We investigated the impact of relative marital power on 72 newlywed couples' endocrinological responses to marital conflict. Marital power was determined by comparing spouse's reports of dependent love for one another. Less powerful spouses displayed elevated adreno-corticotropic hormone ACTH responses to a conflict discussion. Shared power…

  3. Ectopic Adrenocorticotropic Hormone and Corticotropin-Releasing Hormone Co-Secreting Tumors in Children and Adolescents Causing Cushing Syndrome: A Diagnostic Dilemma and How to Solve It

    PubMed Central

    Karageorgiadis, Alexander S.; Papadakis, Georgios Z.; Biro, Juliana; Keil, Meg F.; Lyssikatos, Charalampos; Quezado, Martha M.; Merino, Maria; Schrump, David S.; Kebebew, Electron; Patronas, Nicholas J.; Hunter, Maya K.; Alwazeer, Mouhammad R.; Karaviti, Lefkothea P.; Balazs, Andrea E.; Stratakis, Constantine A.

    2015-01-01

    Context: Ectopic ACTH/CRH syndrome is a rare cause of Cushing syndrome (CS), especially in children. The localization, work-up, and management of ACTH/CRH-secreting tumors are discussed. Setting: A retrospective study was conducted of patients under 21 years of age evaluated at the National Institutes of Health (NIH) for CS and diagnosed with ectopic ACTH/CRH-secreting tumors during the period 2009–2014. Patients: Seven patients with ectopic ACTH/CRH CS are included in this study with a median age 13.6 years (range 1–21), and 3 are female. Measurements: Clinical, biochemical, radiological features, treatment, and histological findings are described. Results: Seven patients were found to have ACTH/CRH-secreting tumors, all with neuroendocrine features. The site of the primary lesion varied: pancreas (3), thymus (2), liver (1), right lower pulmonary lobe (1). Patients underwent biochemical evaluation for CS, including diurnal serum cortisol and ACTH levels, urinary free cortisol levels (UFC), and CRH stimulation tests. All patients underwent radiological investigations including MRI, CT, and PET scan; imaging with octreotide and 68 gallium DOTATATE scans were performed in individual cases. Five patients underwent inferior petrosal sinus sampling; 4 patients had sampling for ACTH and CRH levels from additional sites. Three patients underwent trans-sphenoidal surgery (TSS), and 3 patients required bilateral adrenalectomy. Three patients (43%) died due to metastatic disease, demonstrating the high mortality rate. One of the unique findings in these seven patients is that in each case, their neuroendocrine tumors were ultimately proven to be co-secreting ACTH and CRH. This explains the enigmatic presentation, in which 3 patients initially thought to have Cushing's disease (CD) with corresponding pituitary hyperplasia underwent TSS prior to the correct localization of the causative tumor. Conclusions: Ectopic ACTH/CRH co-secreting tumors are extremely rare in children

  4. Comparative Effect of ACTH and Related Peptides on Proliferation and Growth of Rat Adrenal Gland

    PubMed Central

    Lotfi, Claudimara Ferini Pacicco; de Mendonca, Pedro O. R.

    2016-01-01

    Pro-opiomelanocortin (POMC) is a polypeptide precursor known to yield biologically active peptides related to a range of functions. These active peptides include the adrenocorticotropic hormone (ACTH), which is essential for maintenance of adrenal growth and steroidogenesis, and the alpha-melanocyte stimulation hormone, which plays a key role in energy homeostasis. However, the role of the highly conserved N-terminal region of POMC peptide fragments has begun to be unraveled only recently. Here, we review the cascade of events involved in regulation of proliferation and growth of murine adrenal cortex triggered by ACTH and other POMC-derived peptides. Key findings regarding signaling pathways and modulation of genes and proteins required for the regulation of adrenal growth are summarized. We have outlined the known mechanisms as well as future challenges for research on the regulation of adrenal proliferation and growth triggered by these peptides. PMID:27242663

  5. Ectopic Cushing’s syndrome due to retroperitoneal ACTH-producing paragangliomas

    PubMed Central

    Chen, Fan; Wang, Xiangyu; Wang, Yang; Meng, Hui; Hou, Xinguo; Zhu, Yaofeng; Gao, Wei; Jiang, Xuewen; Chen, Shouzhen; Zhang, Zhaocun; Zou, Zhichuan; He, Tianyi; Yang, Yue; Zhu, Kejia; Wang, Yong; Liu, Yaxiao; Cui, Jianfeng; Shi, Benkang; Yin, Gang

    2016-01-01

    Extra-adrenal pheochromocytomas, or paragangliomas, are rare tumours that derive from extra-adrenal chromaffin cells. Cushing’s syndrome (CS) caused by paragangliomas is extremely rare. We report a 53-year-old man with hypertension, diabetes, and symptoms of hypokalemia. Computer tomography (CT) revealed two retroperitoneal masses and bilateral adrenal hyperplasia. Together with the laboratory examinations, ectopic CS caused by multiple paragangliomas was highly suspected. The patient underwent resections of retroperitoneal tumours, left kidney, and left adrenal; postoperative histopathology confirmed two paragangliomas that were both positively stained for adrenocorticotropic hormone (ACTH). He got clinical and biochemical recoveries without any recurrent evidence at the nine-month followup. PMID:27695589

  6. Cushing's syndrome secondary to ectopic ACTH secretion from carcinoid tumor within an ovarian mature teratoma: a case report and review of the literature.

    PubMed

    Huang, Baoyou; Wu, Xueqing; Zhou, Qing; Hu, Yan; Zhao, Hongqin; Zhu, Hua; Zhang, Qian; Zheng, Feiyun

    2014-03-01

    A 46-year-old woman with Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion caused by primary ovarian mature teratoma with carcinoid components was presented in our case. The patient manifested sustained hypercortisolemia without circadian rhythm and a lack of suppression of either low-dose dexamethasone suppression test (LDDST) or high-dose dexamethasone suppression test (HDDST). There was no evidence of a pituitary mass or secretion of other hormones. After careful clinical evaluation, no other tumor masses were found. Resection of the ovarian tumors led to sharp reduction of serum ACTH and cortisol concentrations. Immunohistochemistry showed positivity in CgA, Syn, CK, NSE. To the best of our knowledge, there are rare reports of an ACTH-secreting carcinoid components located in an ovarian mature teratoma, and bilateral ovarian mature teratoma makes it rarer.

  7. Adrenocortical response to low-dose ACTH test in female patients with rheumatoid arthritis.

    PubMed

    Radikova, Zofia; Rovensky, Jozef; Vlcek, Miroslav; Penesova, Adela; Kerlik, Jana; Vigas, Milan; Imrich, Richard

    2008-12-01

    Alterations in adrenal steroid production have been suggested in females with rheumatoid arthritis (RA). The aim of the present study was to assess adrenocortical function in RA females. We examined 11 female RA patients (RA: age 30 +/- 2 years, BMI 21.0 +/- 0.7 kg/m(2)) and 10 matched healthy controls (C: age 31 +/- 1 years, BMI 21.6 +/- 0.6 kg/m(2)). Low-dose adrenocorticotropic hormone (ACTH) test (i.v. bolus of 1 microg synthetic ACTH) was performed at 10.00 h with blood sampling every 15 min for 90 min. Cortisol, 17-OH-progesterone (17OHP), androstenedione (ASD), and dehydroepiandrosterone (DHEA) were assayed in plasma. Baseline cortisol levels were higher in RA patients (RA: 385 +/- 38 versus C: 229 +/- 28 nmol/L, P= 0.007). In both study groups, ACTH administration increased all the four steroids measured (P < 0.001). Cortisol response to ACTH administration was diminished in RA patients when compared to controls (Delta(max): 284 +/- 24 in RA versus 424 +/- 31 nmol/L in C, P= 0.002). ACTH-induced maximal rise in plasma DHEA was significantly lower in RA patients when compared to controls (Delta(max): 2.59 +/- 0.68 in RA versus 5.57 +/- 1.25 ng/mL in C, P= 0.015). No significant between-groups differences were found in responses of ASD or 17OHP. The molar ratio of ASD:cortisol was significantly lower (P < 0.05) in RA patients at base line, but did not differ during ACTH test. After ACTH bolus, the cortisol:17OHP ratio decreased significantly in the RA group (P < 0.001), whereas there was no change in the control group. The present results show decreased secretion of cortisol and DHEA in RA patients in response to ACTH, suggesting a subtle HPA hypofunction at the adrenocortical level.

  8. ACTH-producing neuroendocrine tumor of the pancreas: a case report and literature review

    PubMed Central

    Byun, Justin; Kim, Sung Hyun; Jeong, Hyang Sook; Rhee, Yumie; Lee, Woo Jung

    2017-01-01

    Tumors that arise from the endocrine pancreas, or the islets of pancreas, are called pancreatic neuroendocrine tumors (NETs). Pancreatic NET have an incidence of <0.1 per one million persons, and can lead to secretion of ectopic adrenocorticotropic hormone (ACTH). Herein, we presented a case of patient with Cushing's syndrome as a result of ACTH-producing pancreatic NET, who underwent successful laparoscopic distal pancreatosplenectomy. A 40-year-old Korean female patient with ophthalmologic discomfort, osteoporosis, and unexplained hypokalemia was admitted to our hospital. Under the suspicion of ACTH producing pancreatic NET after the diagnostic workup, we decided to perform surgical resection. Laparoscopic distal pancreatosplenectomy was performed; and the pathological examination revealed a 1.5 cm-sized grade 2 neuroendocrine tumor of the pancreas, which was encapsulated within the pancreatic parenchyma. After the operation, the patient no longer displayed cushingoid features. ACTH-producing pancreatic NET is rare, but can be one of the causes of Cushing's syndrome. Surgical resection is a feasible option in treating ACTH-producing pancreatic NET. PMID:28317048

  9. Effects of the 5-HT(1A) Receptor Agonist Tandospirone on ACTH-Induced Sleep Disturbance in Rats.

    PubMed

    Tsutsui, Ryuki; Shinomiya, Kazuaki; Sendo, Toshiaki; Kitamura, Yoshihisa; Kamei, Chiaki

    2015-01-01

    The aim of this study was to compare the effect of the serotonin (5-HT)1A receptor agonist tandospirone versus that of the benzodiazepine hypnotic flunitrazepam in a rat model of long-term adrenocorticotropic hormone (ACTH)-induced sleep disturbance. Rats implanted with electrodes for recording electroencephalogram and electromyogram were injected with ACTH once daily at a dose of 100 µg/rat. Administration of ACTH for 10 d caused a significant increase in sleep latency, decrease in non-rapid eye movement (non-REM) sleep time, and increase in wake time. Tandospirone caused a significant decrease in sleep latency and increase in non-REM sleep time in rats treated with ACTH. The effect of tandospirone on sleep patterns was antagonized by the 5-HT1A receptor antagonist WAY-100635. In contrast, flunitrazepam had no significant effect on sleep parameters in ACTH-treated rats. These results clearly indicate that long-term administration of ACTH causes sleep disturbance, and stimulating the 5-HT1A receptor by tandospirone may be efficacious for improving sleep in cases in which benzodiazepine hypnotics are ineffective.

  10. Effects of imipramine and bupropion on the duration of immobility of ACTH-treated rats in the forced swim test: involvement of the expression of 5-HT2A receptor mRNA.

    PubMed

    Kitamura, Yoshihisa; Fujitani, Yoshika; Kitagawa, Kouhei; Miyazaki, Toshiaki; Sagara, Hidenori; Kawasaki, Hiromu; Shibata, Kazuhiko; Sendo, Toshiaki; Gomita, Yutaka

    2008-02-01

    We examined the effect of chronic administration of imipramine and bupropion, monoamine reuptake inhibitors, on the duration of immobility in the forced swim test and serotonin (5-HT)(2A) receptor function in the form of 5-HT(2A) receptor mRNA levels in rats chronically treated with adrenocorticotropic hormone (ACTH). The immobility-decreasing effect of bupropion without imipramine did not influence the chronic ACTH treatment. The effect on the expression of 5-HT(2A) receptor mRNA of chronic ACTH treatment was decreased by bupropion, but not imipramine. These results suggest that bupropion has the effect of reducing immobility time in the forced swim test in the tricyclic antidepressant-resistant depressive model induced by chronic ACTH treatment in rats, and that decreased 5-HT(2A) receptor mRNA levels may be involved in this phenomenon.

  11. Liquid chromatography-tandem mass spectrometry analysis of human adrenal vein corticosteroids before and after ACTH stimulation

    PubMed Central

    Nakamura, Yasuhiro; Rege, Juilee; Satoh, Fumitoshi; Morimoto, Ryo; Kennedy, Michael R; Ahlem, Clarence N; Honma, Seijiro; Sasano, Hironobu; Rainey, William E

    2014-01-01

    Context Although steroid hormones produced by the adrenal gland play critical roles in human physiology, a detailed quantitative analysis of the steroid products has not been reported. The current study uses a single methodology (liquid chromatography-tandem mass spectrometry, LC-MS/MS) to quantify ten corticosteroids in adrenal vein (AV) samples pre and post adrenocorticotropic hormone (ACTH) stimulation. Design/methods Three men and six women with a diagnosis of an adrenal aldosterone-producing adenoma (APA) were included in the study. Serum was collected from the iliac vein (IV) and the adrenal vein (AV) contralateral to the diseased adrenal. Samples were collected, before and after administration of ACTH. LC-MS/MS was then used to quantify serum concentrations of unconjugated corticosteroids and their precursors. Results Prior to ACTH stimulation the four most abundant steroids in AV were cortisol (90%), cortisone (4%), corticosterone (3%) and 11-deoxycortisol (0.8%). Post ACTH administration, cortisol remained the major adrenal product (79%), however, corticosterone became the second most abundantly produced adrenal steroid (11%) followed by pregnenolone (2.5%) and 17α-hydroxypregnenolone (2%). ACTH significantly increased the absolute adrenal output of all ten corticosteroids measured (P<0.05). The four largest post ACTH increases were pregnenolone (300-fold), progesterone (199-fold), 17α-hydroxypregnenolone (187-fold) and deoxycorticosterone (82-fold). Conclusion Using LC-MS/MS we successfully measured 10 corticosteroids in peripheral and adrenal vein serum samples under pre and post ACTH stimulation. This study demonstrates the primary adrenal steroid products and their response to ACTH. PMID:22150161

  12. Acylated ghrelin as provocative test for the diagnosis of ACTH deficiency in patients with hypothalamus-pituitary disease.

    PubMed

    Gasco, Valentina; Berton, Alessandro; Caprino, Mirko Parasiliti; Karamouzis, Ioannis; Maccario, Mauro; Ghigo, Ezio; Grottoli, Silvia

    2015-11-01

    The insulin tolerance test (ITT) is the gold standard to evaluate adrenocorticotropic hormone (ACTH) insufficiency. However, alternative tests have been proposed such as metyrapone, glucagon, and ACTH stimulation test. We determined the diagnostic reliability of testing with ghrelin, the natural GH secretagogue that is a potent stimulus exploring the integrity of hypothalamic-pituitary-adrenal axis. We studied the ACTH and cortisol response to acylated ghrelin in 49 patients with history of pituitary disease. The best cortisol and ACTH cut offs to ghrelin test, defined as those with the best sensitivity (SE) and specificity (SP), were identified using the ROC analysis. We also compared accuracy of ghrelin test with that of a simple and cheap test like basal cortisol and ACTH levels. The best cortisol and ACTH cut offs to ghrelin test were ≤11.6 µg/dl (SE 86.4%, SP 77.8%) and ≤32.5 pg/ml (SE 72.7%, SP 51.9%), respectively; the best basal cortisol and ACTH cut offs were ≤10.7 µg/dl (SE 90.9%, SP 70.4%) and ≤25.0 pg/ml (SE 85%, SP 37%), respectively. The diagnostic accuracy was 81.6, 60.9, 79.6, and 57.4%, respectively. A comparison between ROC AUC showed a great diagnostic power for cortisol, both stimulated and basal, versus ACTH, both stimulated and basal, but no difference between stimulated and basal cortisol evaluation. Our data show that testing with acylated ghrelin is not a useful diagnostic tool for the diagnosis of central hypocortisolism; particularly ghrelin test adds no more information that basal cortisol evaluation in the diagnosis of ACTH deficiency in patients with hypothalamus-pituitary disease.

  13. Effects of prolonged alcohol exposure on somatotrophs and corticotrophs in adult rats: Stereological and hormonal study.

    PubMed

    Trifunović, Svetlana; Manojlović-Stojanoski, Milica; Ristić, Nataša; Jurijević, Branka Šošić; Balind, Snežana Raus; Brajković, Gordana; Perčinić-Popovska, Florina; Milošević, Verica

    2016-05-01

    Exposure to alcohol alters many physiological processes, including endocrine status. The present study examined whether prolonged alcohol (A) exposure could modulate selected stereological and hormonal aspects of pituitary somatotrophs (growth hormone-GH cells) and corticotrophs (adrenocorticotropic hormone-ACTH cells) in adult rats. Changes in pituitary gland volume; the volume density, total number and volume of GH and ACTH cells following alcohol exposure were evaluated using a stereological system (newCAST), while peripheral GH and ACTH levels were determined biochemically. Our results demonstrated the reduction (p<0.05) of the volume density (37%) and volume of GH cells (29%) in the group A. Also, there was a tendency for the total number of GH cells to be smaller in the group A. Serum GH level was significantly decreased (p<0.05; 70%) in the group A when compared to control values. Moreover, prolonged alcohol exposure induced declines (p<0.05) in volume density (24%) and volume of ACTH cells (29%). The total number of ACTH cells and ACTH level were higher (p<0.05; 42%) in the group A than in control rats. Collectively, these results indicate that prolonged alcohol exposure leads not only to changes in GH and ACTH hormone levels, but also to alterations of the morphological aspects of GH and ACTH cells within the pituitary.

  14. Ectopic ACTH and CRH co-secreting tumor localized by 68Ga-DOTA-TATE PET/CT

    PubMed Central

    Papadakis, Georgios Z.; Bagci, Ulas; Sadowski, Samira M.; Patronas, Nicholas J.; Stratakis, Constantine A.

    2015-01-01

    Diagnosis of ectopic adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) co-secreting tumors causing Cushing syndrome (CS) is challenging, since these tumors are rare and their diagnosis is frequently confused with Cushing disease (CD), due to the effect of CRH on the pituitary. We report a case of a 21-year-old male who was referred to our institution with persistent hypercortisolemia and CS after undergoing unnecessary transsphenoidal surgery (TSS). 68Ga-DOTA-TATE PET/CT revealed increased tracer uptake in the thymus which was histologically proved to be neuroendocrine tumor (NET) staining positive for ACTH and CRH. Imaging with 18F-FDG PET/CT was not diagnostic. PMID:26018709

  15. Ectopic ACTH and CRH Co-secreting Tumor Localized by 68Ga-DOTA-TATE PET/CT.

    PubMed

    Papadakis, Georgios Z; Bagci, Ulas; Sadowski, Samira M; Patronas, Nicholas J; Stratakis, Constantine A

    2015-07-01

    Diagnosis of ectopic adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) co-secreting tumors causing Cushing syndrome (CS) is challenging because these tumors are rare and their diagnosis is frequently confused with Cushing disease (CD), caused by the effect of CRH on the pituitary. We report a case of a 21-year-old male patient who was referred to our institution with persistent hypercortisolemia and CS after undergoing unnecessary transsphenoidal surgery (TSS). ⁶⁸Ga-DOTA-TATE PET/CT revealed increased tracer uptake in the thymus, which was histologically proven to be a neuroendocrine tumor (NET) that stained positive for ACTH and CRH. Imaging with ¹⁸F-FDG PET/CT was not diagnostic.

  16. ACTH Antagonists

    PubMed Central

    Clark, Adrian John; Forfar, Rachel; Hussain, Mashal; Jerman, Jeff; McIver, Ed; Taylor, Debra; Chan, Li

    2016-01-01

    Adrenocorticotropin (ACTH) acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R), is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP) for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1) Cushing’s disease and ectopic ACTH syndrome – especially while preparing for definitive treatment of a causative tumor, or in refractory cases, or (2) congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article, we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role. PMID:27547198

  17. Effects of ACTH, capture, and short term confinement on glucocorticoid concentrations in harlequin ducks (Histrionicus histrionicus)

    USGS Publications Warehouse

    Nilsson, P.B.; Hollmén, Tuula E.; Atkinson, S.; Mashburn, K.L.; Tuomi, P.A.; Esler, Daniel; Mulcahy, D.M.; Rizzolo, D.J.

    2008-01-01

    Little is known about baseline concentrations of adrenal hormones and hormonal responses to stress in sea ducks, although significant population declines documented in several species suggest that sea ducks are exposed to increased levels of environmental stress. Such declines have been observed in geographically distinct harlequin duck populations. We performed an adrenocorticotropic hormone (ACTH) challenge to evaluate adrenal function and characterize corticosterone concentrations in captive harlequin ducks and investigated the effects of capture, surgery, and short term confinement on corticosterone concentrations in wild harlequin ducks. Harlequin ducks responded to the ACTH challenge with an average three-fold increase in serum corticosterone concentration approximately 90??min post injection, and a four- to five-fold increase in fecal glucocorticoid concentration 2 to 4??h post injection. Serum corticosterone concentrations in wild harlequin ducks increased within min of capture and elevated levels were found for several hours post capture, indicating that surgery and confinement maintain elevated corticosterone concentrations in this species. Mean corticosterone concentrations in wild harlequin ducks held in temporary captivity were similar to the maximum response levels during the ACTH challenge in captive birds. However, large variation among individuals was observed in responses of wild birds, and we found additional evidence suggesting that corticosterone responses varied between hatch year and after hatch year birds. ?? 2008.

  18. ACTH Receptor (MC2R) Specificity: What Do We Know About Underlying Molecular Mechanisms?

    PubMed

    Fridmanis, Davids; Roga, Ance; Klovins, Janis

    2017-01-01

    Coincidentally, the release of this Research Topic in Frontiers in Endocrinology takes place 25 years after the discovery of the adrenocorticotropic hormone receptor (ACTHR) by Mountjoy and colleagues. In subsequent years, following the discovery of other types of mammalian melanocortin receptors (MCRs), ACTHR also became known as melanocortin type 2 receptor (MC2R). At present, five types of MCRs have been reported, all of which share significant sequence similarity at the amino acid level, and all of which specifically bind melanocortins (MCs)-a group of biologically active peptides generated by proteolysis of the proopiomelanocortin precursor. All MCs share an identical -H-F-R-W- pharmacophore sequence. α-Melanocyte-stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH) are the most extensively studied MCs and are derived from the same region. Essentially, α-MSH is formed from the first 13 amino acid residues of ACTH. ACTHR is unique among MCRs because it binds one sole ligand-ACTH, which makes it a very attractive research object for molecular pharmacologists. However, much research has failed, and functional studies of this receptor are lagging behind other MCRs. The reason for these difficulties has already been outlined by Mountjoy and colleagues in their publication on ACTHR coding sequence discovery where the Cloudman S91 melanoma cell line was used for receptor expression because it was a "more sensitive assay system." Subsequent work showed that ACTHR could be successfully expressed only in endogenous MCR-expressing cell lines, since in other cell lines it is retained within the endoplasmic reticulum. The resolution of this methodological problem came in 2005 with the discovery of melanocortin receptor accessory protein, which is required for the formation of functionally active ACTHR. The decade that followed this discovery was filled with exciting research that provided insight into the molecular mechanisms underlying the action of

  19. A case of West syndrome well controlled by very short and low-dose ACTH therapy.

    PubMed

    Kimura, M; Miyamoto, S; Sejima, H; Yamaguchi, S

    1999-02-01

    The case of a 5-month-old boy with tuberous sclerosis and West syndrome is reported. Tonic spasms were noted from the age of 4 months. High-dose pyridoxal phosphate could not control the seizures completely. Very short and low-dose adrenocorticotropic hormone (ACTH) therapy (i.e. 0.011 mg/kg per dose, 12 times in 20 days) controlled the seizures, while pyridoxal phosphate was on. Early tapering of ACTH was successfully done while abnormal electroencephalogram (EEG) findings remained. Although side effects such as hypertension and brain shrinkage were transiently observed, both the cognitive and seizure prognoses were excellent at the age of 3 years and 2 months. The good response to a small dosage of ACTH might be due to some responsiveness of the high-dose pyridoxal phosphate and the underlying cause of tuberous sclerosis with normal development before onset. The present case illustrates that the duration and dosage of ACTH therapy in West syndrome should be modified according to the individual's requirements.

  20. Imipramine-induced c-Fos expression in the medial prefrontal cortex is decreased in the ACTH-treated rats.

    PubMed

    Li, Bingjin; Suemaru, Katsuya; Kitamura, Yoshihisa; Gomita, Yutaka; Araki, Hiroaki; Cui, Ranji

    2013-11-01

    Previous studies have shown that the antidepressive-like effect of tricyclic antidepressants is blocked by repeated treatments with adrenocorticotropic hormone (ACTH). However, little is known about the neuroanatomy underlying the mechanism of the imipramine treatment-resistant depression model. In the present study, first experimental evidence showed no significant difference of the serum imipramine concentrations between the saline and ACTH-treated rats. In further study, imipramine produced significant increases in the c-Fos expression in the medial prefrontal cortex (mPFC), the dentate gyrus of the hippocampus (DGH), and the central nucleus of the amygdala (CeA), in rats repeatedly treated with saline. The imipramine-increased c-Fos immunoreactivity was suppressed in the mPFC of rats repeatedly treated with ACTH. However, there was no significant difference in c-Fos expression in the DGH and CeA between ACTH- and saline-treated rats. These results suggest that the mPFC is maybe involved in effects of the imipramine in the ACTH-treated rats.

  1. Influence of ACTH on the effects of imipramine, desipramine and lithium on duration of immobility of rats in the forced swim test.

    PubMed

    Kitamura, Yoshihisa; Araki, Hiroaki; Gomita, Yutaka

    2002-01-01

    We examined the effects of adrenocorticotropic hormone (ACTH) on the immobilization of rats in the forced swim test with the administration of imipramine, desipramine, or lithium. A single administration of either imipramine (10-30 mg/kg, i.p.) or desipramine (30 mg/kg, i.p.) significantly decreased the duration of immobility in normal rats in a dose-dependent manner. Lithium (10-100 mg/kg, p.o.), however, had no affect on the performance of rats in the forced swim test. ACTH (100 microg/day), administered subcutaneously to rats for 1, 3, 7, and 14 days, had no apparent effect on the duration of immobility in this test. The immobility-decreasing effect induced by a single administration of either imipramine (10-30 mg/kg, i.p.) or desipramine (30 mg/kg, i.p.) was blocked by chronic administration of ACTH for 3-14 days. The reduction of immobility, induced by chronic administration of imipramine (10 mg/kg, i.p.) for 15 days, was blocked by treatment with ACTH for 14 days. When lithium (100 mg/kg, p.o.) was administered for 15 days concurrently with imipramine (10 mg/kg, i.p.), we observed a significant decrease in immobility in rats treated with ACTH for 14 days. We suggest that chronic treatment of rats with ACTH may prove to be an effective model of tricyclic antidepressants-treatment-resistant depression.

  2. Inhibition of ACTH Release by Peptide Hormones: Molecular Mechanisms and Possible Role as Anti-Stress Factors

    DTIC Science & Technology

    1989-11-16

    somatostatin (SRIF) may be a non- steriod inhibitor of Ar.TH release. The goals of the proposal were to examine the structure of the SRIF receptor and determine...major objective of the research proposal was the identification of non- steriodal factors which inhibit ACTH release and may be useful in the treatment

  3. Vasopressin and angiotensin II in reflex regulation of ACTH, glucocorticoids, and renin: effect of water deprivation

    NASA Technical Reports Server (NTRS)

    Brooks, V. L.; Keil, L. C.

    1992-01-01

    Angiotensin II (ANG II) and vasopressin participate in baroreflex regulation of adrenocorticotropic hormone (ACTH), glucocorticoid, and renin secretion. The purpose of this study was to determine whether this participation is enhanced in water-deprived dogs, with chronically elevated plasma ANG II and vasopressin levels, compared with water-replete dogs. The baroreflex was assessed by infusing increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1) in both groups of animals. To quantitate the participation of ANG II and vasopressin, the dogs were untreated or pretreated with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or combined V1/V2-vasopressin antagonist, either alone or in combination. The findings were as follows. 1) Larger reflex increases in ANG II, vasopressin, and glucocorticoids, but not ACTH, were produced in water-deprived dogs compared with water-replete dogs. 2) ANG II blockade blunted the glucocorticoid and ACTH responses to hypotension in water-deprived dogs, but not water-replete dogs. In contrast, vasopressin blockade reduced the ACTH response only in water-replete dogs. 3) Vasopressin or combined vasopressin and ANG II blockade reduced the plasma level of glucocorticoids related either to the fall in arterial pressure or to the increase in plasma ACTH concentration in water-replete dogs, and this effect was enhanced in water-deprived dogs. 4) In both water-deprived and water-replete animals, saralasin and/or a V1-antagonist increased the renin response to hypotension, but a combined V1/V2-antagonist did not. These results reemphasize the importance of endogenous ANG II and vasopressin in the regulation of ACTH, glucocorticoid, and renin secretion.(ABSTRACT TRUNCATED AT 250 WORDS).

  4. Modulation of adrenocorticotrophin hormone (ACTH)-induced expression of stress-related genes by PUFA in inter-renal cells from European sea bass (Dicentrarchus labrax).

    PubMed

    Montero, Daniel; Terova, Genciana; Rimoldi, Simona; Tort, Lluis; Negrin, Davinia; Zamorano, María Jesús; Izquierdo, Marisol

    2015-01-01

    Dietary fatty acids have been shown to exert a clear effect on the stress response, modulating the release of cortisol. The role of fatty acids on the expression of steroidogenic genes has been described in mammals, but little is known in fish. The effect of different fatty acids on the release of cortisol and expression of stress-related genes of European sea bass (Dicentrarchus labrax) head kidney, induced by a pulse of adenocorticotrophin hormone (ACTH), was studied. Tissue was maintained in superfusion with 60 min of incubation with EPA, DHA, arachidonic acid (ARA), linoleic acid or α-linolenic acid (ALA) during 490 min. Cortisol was measured by RIA. The quantification of stress-related genes transcripts was conducted by One-Step TaqMan real-time RT-PCR. There was an effect of the type of fatty acid on the ACTH-induced release of cortisol, values from ALA treatment being elevated within all of the experimental period. The expression of some steroidogenic genes, such as the steroidogenic acute regulatory protein (StAR) and c-fos, were affected by fatty acids, ALA increasing the expression of StAR after 1 h of ACTH stimulation whereas DHA, ARA and ALA increased the expression of c-fos after 20 min. ARA increased expression of the 11β-hydroxylase gene. Expression of heat shock protein 70 (HSP70) was increased in all the experimental treatments except for ARA. Results corroborate previous studies of the effect of different fatty acids on the release of cortisol in marine fish and demonstrate that those effects are mediated by alteration of the expression of steroidogenic genes.

  5. Muscle transcriptome response to ACTH administration in a free-ranging marine mammal

    PubMed Central

    Champagne, Cory D.; Preeyanon, Likit; Ortiz, Rudy M.; Crocker, Daniel E.

    2015-01-01

    While much of our understanding of stress physiology is derived from biomedical studies, little is known about the downstream molecular consequences of adaptive stress responses in free-living animals. We examined molecular effectors of the stress hormones cortisol and aldosterone in the northern elephant seal, a free-ranging study system in which extreme physiological challenges and cortisol fluctuations are a routine part of life history. We stimulated the neuroendocrine stress axis by administering exogenous adrenocorticotropic hormone (ACTH) and examined the resultant effects by measuring corticosteroid hormones, metabolites, and gene expression before, during, and following administration. ACTH induced an elevation in cortisol, aldosterone, glucose, and fatty acids within 2 h, with complete recovery observed within 24 h of administration. The global transcriptional response of elephant seal muscle tissue to ACTH was evaluated by transcriptomics and involved upregulation of a highly coordinated network of conserved glucocorticoid (GC) target genes predicted to promote metabolic substrate availability without causing deleterious effects seen in laboratory animals. Transcriptional recovery from ACTH was characterized by downregulation of GC target genes and restoration of cell proliferation, metabolism, and tissue maintenance pathways within 24 h. Differentially expressed genes included several adipokines not previously described in muscle, reflecting unique metabolic physiology in fasting-adapted animals. This study represents one of the first transcriptome analyses of cellular responses to hypothalamic-pituitary-adrenal axis stimulation in a free-living marine mammal and suggests that compensatory, tissue-sparing mechanisms may enable marine mammals to maintain cortisol and aldosterone sensitivity while avoiding deleterious long-term consequences of stress. PMID:26038394

  6. Glucagon-like peptide-2 but not imipramine exhibits antidepressant-like effects in ACTH-treated mice.

    PubMed

    Iwai, Takashi; Ohnuki, Tomoko; Sasaki-Hamada, Sachie; Saitoh, Akiyoshi; Sugiyama, Azusa; Oka, Jun-Ichiro

    2013-04-15

    We investigated the effectiveness of glucagon-like peptide-2 (GLP-2) against refractory depression in adrenocorticotropic hormone (ACTH)-treated mice as a model of tricyclic antidepressant (TCA)-resistant depression. Chronic ACTH treatment (0.45 mg/kg, s.c., 14 days) weakened the antidepressant-like effects of imipramine (20 mg/kg, i.p., 6 days) in the forced-swim test (FST). Conversely, GLP-2 (3 μg/mice, i.c.v., 6 days) induced antidepressant-like effects in the ACTH-treated mice in the FST. ACTH-treatment increased basal serum corticosterone levels, with an additional increase induced by the FST. Imipramine or GLP-2 had no effect on the basal corticosterone level, but GLP-2 attenuated the additional increase caused by the FST. Moreover, GLP-2 increased 5-HT levels, but not 5-HIAA. These results suggest that GLP-2 induced antidepressant-like effects under imipramine-resistant conditions through increase in 5-HT levels.

  7. Effects of pramipexole on the duration of immobility during the forced swim test in normal and ACTH-treated rats.

    PubMed

    Kitagawa, Kouhei; Kitamura, Yoshihisa; Miyazaki, Toshiaki; Miyaoka, Junya; Kawasaki, Hiromu; Asanuma, Masato; Sendo, Toshiaki; Gomita, Yutaka

    2009-07-01

    The dopamine D2/D3 receptor agonist pramipexole has clinically been proven to improve depression or treatment-resistant depression. However, the involvement of the dopamine receptor system on the effect of pramipexole on depression remains unclear. We examined the influence of pramipexole on the duration of immobility during the forced swim test in normal and adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which pramipexole acts in this model was explored specifically in relation to the site of action through the use of microinjections into the intramedial prefrontal cortex and nucleus accumbens. Pramipexole (0.3-1 mg/kg) significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by L-741,626, a D2 receptor antagonist, and nafadotride, a D3 receptor antagonist, in normal rats. Furthermore, infusions of pramipexole into the intranucleus accumbens, but not the medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Taken together, the results of these experiments suggested that pramipexole, administered into the intranucleus accumbens rather than the medial prefrontal cortex, exerted an antidepressant-like effect on ACTH-treated rats via the dopaminergic system. The immobility-decreasing effect of pramipexole may be mediated by dopamine D2 and D3 receptors.

  8. Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (Interleukin Beta, Interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans

    SciTech Connect

    Girinsky, T.A.; Pallardy, M.; Comoy, E.; Benassi, T.; Roger, R.; Ganem, G.; Socie, G.; Cossett, J.M.; Magdelenat, H.

    1994-09-01

    Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamopituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is a common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cyctokines induced by ionizing radiation remain to be determined. 25 refs., 1 fig.

  9. Neuropeptide Y administration reverses tricyclic antidepressant treatment-resistant depression induced by ACTH in mice.

    PubMed

    Antunes, Michelle S; Ruff, Jossana Rodrigues; de Oliveira Espinosa, Dieniffer; Piegas, Manuela Bastos; de Brito, Maicon Lenon Otenio; Rocha, Kellen Athaíde; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Souza, Leandro Cattelan; Donato, Franciele; Boeira, Silvana Peterini; Jesse, Cristiano R

    2015-07-01

    Depression is one of the most common mental disorders and a primary cause of disability. To better treat patients suffering this illness, elucidation of the underlying psychopathological and neurobiological mechanisms is urgently needed. Based on the above-mentioned evidence, we sought to investigate the effects of neuropeptide Y (NPY) treatment in tricyclic antidepressant treatment-resistant depression induced by adrenocorticotropic hormone (ACTH) administration. Mice were treated with NPY (5.84, 11.7 or 23.4mmol/μl) intracerebroventricularly (i.c.v.) for one or five days. The levels of serum corticosterone, tryptophan (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and indoleamine 2,3-dioxygenase (IDO) activity in the hippocampus were analyzed. The behavioral parameters (depressive-like and locomotor activity) were also verified. This study demonstrated that ACTH administration increased serum corticosterone levels, KYN, 5-HIAA levels, IDO activity (hippocampus), immobility in the forced swimming test (FST) and the latency to feed in the novelty suppressed feeding test (NSFT). In addition, ACTH administration decreased the BDNF and NGF levels in the hippocampus of mice. NPY treatment was effective in preventing these hormonal, neurochemical and behavioral alterations. It is suggested that the main target of NPY is the modulation of corticosterone and neuronal plasticity protein levels, which may be closely linked with pharmacological action in a model of tricyclic antidepressant treatment-resistant depression. Thus, this study demonstrated a protective effect of NPY on the alterations induced by ACTH administration in mice, indicating that it could be useful as a therapy for the treatment of tricyclic antidepressant treatment-resistant depression.

  10. ACTH adenomas transforming their clinical expression: report of 5 cases.

    PubMed

    Zoli, Matteo; Faustini-Fustini, Marco; Mazzatenta, Diego; Marucci, Gianluca; De Carlo, Eugenio; Bacci, Antonella; Pasquini, Ernesto; Lanzino, Giuseppe; Frank, Giorgio

    2015-02-01

    OBJECT Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon. METHODS The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter. RESULTS Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18-51 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma "shifted" to a functioning adenoma and then regressed back to a silent form with spontaneous

  11. Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects

    PubMed Central

    Kim, Y; McGee, S; Czeczor, J K; Walker, A J; Kale, R P; Kouzani, A Z; Walder, K; Berk, M; Tye, S J

    2016-01-01

    Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 μg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg−1) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS; 130 Hz, 100 μA, 90 μS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST (P<0.05). NAc DBS effectively improved FST mobility in ACTH-treated animals (P<0.05). No improvement in mobility was observed for sham control animals (P>0.05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation. PMID:27327257

  12. Association of hormonal responses and performance of student pilots during acceleration training on the human centrifuge

    NASA Astrophysics Data System (ADS)

    Wirth, D.; Rohleder, N.; Welsch, H.

    2005-08-01

    Prediction of student pilots' +Gz tolerance by stress hormone levels would be a useful tool in aviation medicine. The aim of the present study was to analyze the relationship between neuroendocrine parameters with performance during acceleration training on the human centrifuge (HC).We investigated 21 student pilots during self-controlled acceleration training on the HC. Adrenocorticotropic hormone (ACTH), cortisol, epinephrine, and norepinephrine were measured after individual training sessions and at rest. Performance was defined by several characteristics including maximum tolerated acceleration. ACTH and cortisol, were significantly higher 20 minutes after acceleration training compared to the resting condition. Subjects tolerated a maximal acceleration of +6.69 Gz. HPA hormone levels and responses were associated with maximum tolerated acceleration +Gz. These findings support the expectation that acceleration- induced increases in stress hormones may enable the organism to tolerate a higher acceleration and could therefore be used as predictors for acceleration tolerance.

  13. Changes in plasma melanocyte-stimulating hormone, ACTH, prolactin, GH, LH, FSH, and thyroid-stimulating hormone in response to injection of sulpiride, thyrotropin-releasing hormone, or vehicle in insulin-sensitive and -insensitive mares.

    PubMed

    Valencia, N Arana; Thompson, D L; Mitcham, P B

    2013-05-01

    Six insulin-sensitive and 6 insulin-insensitive mares were used in a replicated 3 by 3 Latin square design to determine the pituitary hormonal responses (compared with vehicle) to sulpiride and thyrotropin-releasing hormone (TRH), 2 compounds commonly used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. Mares were classified as insulin sensitive or insensitive by their previous glucose responses to direct injection of human recombinant insulin. Treatment days were February 25, 2012, and March 10 and 24, 2012. Treatments were sulpiride (racemic mixture, 0.01 mg/kg BW), TRH (0.002 mg/kg BW), and vehicle (saline, 0.01 mL/kg BW) administered intravenously. Blood samples were collected via jugular catheters at -10, 0, 5, 10, 20, 30, 45, 60, 90, and 120 min relative to treatment injection. Plasma ACTH concentrations were variable and were not affected by treatment or insulin sensitivity category. Plasma melanocyte-stimulating hormone (MSH) concentrations responded (P < 0.01) to both sulpiride and TRH injection and were greater (P < 0.05) in insulin-insensitive mares than in sensitive mares. Plasma prolactin concentrations responded (P < 0.01) to both sulpiride and TRH injection, and the response was greater (P < 0.05) for sulpiride; no effect of insulin sensitivity was observed. Plasma thyroid-stimulating hormone (TSH) concentrations responded (P < 0.01) to TRH injection only and were higher (P < 0.05) in insulin-sensitive mares in almost all time periods. Plasma LH and FSH concentrations varied with time (P < 0.05), particularly in the first week of the experiment, but were not affected by treatment or insulin sensitivity category. Plasma GH concentrations were affected (P < 0.05) only by day of treatment. The greater MSH responses to sulpiride and TRH in insulin-insensitive mares were similar to, but not as exaggerated as, those observed by others for PPID horses. In addition, the reduced TSH concentrations in insulin-insensitive mares are

  14. Effects of bupropion on the forced swim test and release of dopamine in the nucleus accumbens in ACTH-treated rats.

    PubMed

    Kitamura, Yoshihisa; Yagi, Takahiko; Kitagawa, Kouhei; Shinomiya, Kazuaki; Kawasaki, Hiromu; Asanuma, Masato; Gomita, Yutaka

    2010-08-01

    The dopamine reuptake inhibitor bupropion has clinically been proven to improve depression and treatment-resistant depression. We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which bupropion acts in this model was explored specifically in relation to the site of action through the use of microinjections into the medial prefrontal cortex and nucleus accumbens. Bupropion significantly decreased the duration of immobility in normal and ACTH-treated rats. This effect was blocked by D2 and D3 receptor antagonists in normal rats. Furthermore, infusions of bupropion into the nucleus accumbens, but not medial prefrontal cortex, decreased the immobility of normal and ACTH-treated rats during the forced swim test. Bupropion treatment plus repeated ACTH treatment significantly increased the extracellular dopamine concentration. These findings suggest the antidepressant-like effect of bupropion to be related to levels of dopamine in the rat nucleus accumbens.

  15. ACTH Receptor (MC2R) Specificity: What Do We Know About Underlying Molecular Mechanisms?

    PubMed Central

    Fridmanis, Davids; Roga, Ance; Klovins, Janis

    2017-01-01

    Coincidentally, the release of this Research Topic in Frontiers in Endocrinology takes place 25 years after the discovery of the adrenocorticotropic hormone receptor (ACTHR) by Mountjoy and colleagues. In subsequent years, following the discovery of other types of mammalian melanocortin receptors (MCRs), ACTHR also became known as melanocortin type 2 receptor (MC2R). At present, five types of MCRs have been reported, all of which share significant sequence similarity at the amino acid level, and all of which specifically bind melanocortins (MCs)—a group of biologically active peptides generated by proteolysis of the proopiomelanocortin precursor. All MCs share an identical –H–F–R–W– pharmacophore sequence. α-Melanocyte-stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH) are the most extensively studied MCs and are derived from the same region. Essentially, α-MSH is formed from the first 13 amino acid residues of ACTH. ACTHR is unique among MCRs because it binds one sole ligand—ACTH, which makes it a very attractive research object for molecular pharmacologists. However, much research has failed, and functional studies of this receptor are lagging behind other MCRs. The reason for these difficulties has already been outlined by Mountjoy and colleagues in their publication on ACTHR coding sequence discovery where the Cloudman S91 melanoma cell line was used for receptor expression because it was a “more sensitive assay system.” Subsequent work showed that ACTHR could be successfully expressed only in endogenous MCR-expressing cell lines, since in other cell lines it is retained within the endoplasmic reticulum. The resolution of this methodological problem came in 2005 with the discovery of melanocortin receptor accessory protein, which is required for the formation of functionally active ACTHR. The decade that followed this discovery was filled with exciting research that provided insight into the molecular mechanisms underlying

  16. Hormonal responses of metoclopramide-treated subjects experiencing nausea or emesis during parabolic flight

    NASA Technical Reports Server (NTRS)

    Kohl, Randall L.

    1987-01-01

    The concentrations of adrenocorticotropic hormone (ACTH), vasopressin (AVP), epinephrine (EPI), and norepinephrine (NE) in 22 subjects administered 10 to 20 mg of metoclopramide prior to parabolic flight are measured. The effect of metoclopramide on motion sickness is examined. It is observed that metoclopramide is ineffective in the modulation of motion sickness due to stressful linear and angular acceleration and orbital flight, and it does not affect serum hormones prior to parabolic flight. It is detected that the serum level of AVP declines following emesis induced by parabolic flight and stressful angular acceleration; the serum levels of ACTH and EPI are elevated by parabolic flight and stressful angular acceleration; and serum NE is significantly elevated immediately following emesis. The possible roles of these hormones in the etiology of space motion sickness are discussed.

  17. Neurotrophin gene expression in rat brain under the action of Semax, an analogue of ACTH 4-10.

    PubMed

    Agapova, T Y; Agniullin, Y V; Shadrina, M I; Shram, S I; Slominsky, P A; Lymborska, S A; Myasoedov, N F

    2007-05-01

    The heptapeptide Semax, an analogue of the N-terminal adrenocorticotropic hormone fragment (4-10) (ACTH(4-10)), has been shown to exert a number of neuroprotective effects. There are some investigations that connected these effects with the increase of neurotrophin gene expression under the peptide drug application in neuron cell cultures [M.I. Shadrina, O.V. Dolotov, I.A. Grivennikov, P.A. Slominsky, L.A. Andreeva, L.S. Inozemtseva, S.A. Limborska, N.F. Myasoedov, Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analogue, Neurosci. Lett. 308 (2001) (2) 115-118]. In this work, we examined the action of Semax on rapid changes of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in vivo. Male Wistar rats were treated for 1h with Semax (50 microg/kg, single intranasal application) and neurotrophin gene expression in rat brain was analyzed by real-time polymerase chain reaction (PCR). It was revealed that an intranasal application of Semax increased the expression of both neurotrophin genes in rat hippocampus. Bdnf gene expression also increased in the brainstem and cerebellum. Ngf gene expression decreased in rat frontal cortex. Thus, Semax induces rapid, gene- and region-specific changes in neurotrophin gene expression in normal rat brain.

  18. A case of West syndrome with atypical massive gray matter heterotopia that is well controlled by ACTH therapy.

    PubMed

    Kuwahara, M; Shima, M; Nakai, H; Nishino, M; Fukuzumi, A; Yoshioka, A

    1996-06-01

    A 4 month old female infant with atypical asymmetrical massive gray matter heterotopia diagnosed as West syndrome is described. Her seizure initially appeared as afebrile general tonic and clonic convulsion and progressed to typical West syndrome consisting of clusters of myoclonic spasms of the extremities, mainly on the left side, accompanied by head and eye deviation to the right side. Electroencephalogram (EEG) presented typical hypsarrhythmia and cranial computerized tomography (CT) and magnetic resonance imaging (MRI) showed massive heterotopic gray matter in the right hemisphere with the same density or intensity as cortical gray matter. Single photon emission computed tomography (SPECT), using N-isopropyl-p-123I-iodoamphetamine (123 I-IMP), demonstrated decreased blood flow in the ectopic lesion. Although clinical response to several anti-epileptic drugs was poor, her seizures were well controlled by relatively low dose adrenocorticotropic hormone (ACTH) therapy of 0.015 mg/kg per day followed by a combination of valproic acid and clonazepam.

  19. Nocardiosis in ectopic ACTH syndrome: A case report and review of 11 cases from the literature

    PubMed Central

    Xu, Lichen; Xu, Qiaomai; Yang, Meifang; Gao, Hainv; Xu, Mingzhi; Ma, Weihang

    2016-01-01

    Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) associated with nocardiosis is rare, and little information is available regarding its clinical characteristics. In this study, the case of a 35-year-old male patient who showed significant cushingoid features and had a cough with yellow phlegm for 1 month is described. Pulmonary computed tomography (CT) scanning and 18F-fluorodeoxyglucose positron emission tomography combined with CT identified two different lesions in the mediastinum and pulmonary region, respectively. The lesion in the mediastinum was finally diagnosed as an ACTH-secreting mediastinal paraganglioma via biopsy. The sputum culture confirmed pulmonary nocardiosis. The patient was effectively treated with complete tumor resection following the treatment of nocardiosis using trimethoprim-sulfamethoxazole. Following the present case, 11 additional cases of nocardiosis in EAS were identified in the literature and their clinical characteristics were compared and evaluated. It may be concluded that, although Nocardia remains a rare opportunistic infection pathogen in EAS, it is necessary to consider nocardiosis as a diagnosis for patients with pulmonary imaging findings of cavity, consolidation or nodule, particularly when there are brain and extra-pulmonary lesions as well as a poor response to regular treatment. PMID:28105096

  20. Cytokine and hormonal changes after cholecystectomy. Effect of ibuprofen pretreatment.

    PubMed Central

    Chambrier, C; Chassard, D; Bienvenu, J; Saudin, F; Paturel, B; Garrigue, C; Barbier, Y; Boulétreau, P

    1996-01-01

    OBJECTIVE: Surgical stress induces hormonal and cytokine responses proportional to the extent of the injury. Therefore, the authors assessed the effect of ibuprofen pretreatment on metabolic and hormonal changes after surgery. SUMMARY BACKGROUND DATA: Postoperative administration of cyclo-oxygenase inhibitor reduces cytokine production and nitrogen losses. METHODS: The authors studied the plasma hormones and metabolic and cytokines changes after perioperative ibuprofen administration in 22 patients undergoing cholecystectomy under inhalational anesthesia. Suppositories containing ibuprofen (500 mg) or placebo were administered 12 and 2 hours before surgery, and every 8 hours until the third postoperative day. Blood samples were collected 24 and 2 hours before surgery and 2, 4, 6, 24, 48, and 72 hours after surgery for glucose, C-reactive protein, leukocytes, adrenocorticotropic hormone (ACTH), cortisol, tumor necrosis factor, and interleukin-1 and interleukin-6 determinations. RESULTS: In both groups, plasma cortisol levels remained elevated for 3 days, whereas plasma ACTH levels returned to the basal level at day 1. The ACTH (p < 0.01), cortisol (p < 0.01), and glucose changes (p < 0.001) were smaller in the ibuprofen group and their duration was shorter. The interleukin-6 levels increased gradually after skin incision until the sixth hour and were significantly lower (p < 0.05) in the ibuprofen group. CONCLUSION: Ibuprofen pretreatment in perioperative course is able to reduce the endocrine response and cytokine release. Therefore, ibuprofen may be useful in decreasing the stress response in severely surgical patients. PMID:8757381

  1. In vivo effect of insulin on the hormone production of immune cells in mice - gender differences.

    PubMed

    Pállinger, Éva; Csaba, György

    2014-12-01

    The immune cells of rat and man synthesize, store and secrete hormones, characteristic to the endocrine glands. In the present experiments female and male CD1 mice were treated with 10 IU/kg insulin sc. (the controls with normal saline) and after 30 min peritoneal fluid was gained. The cells of the peritoneal fluid (lymphocytes and the monocyte-granulocyte group) were studied by immunocytochemical flow-cytometry to adrenocorticotropic hormone (ACTH), triiodothyronine (T3), histamine and serotonin content. In the female mice each hormone level was significantly lower in the insulin-treated animals, except histamine in the monocyte-granulocyte group. In the insulin-treated male animals, the hormone levels were similar to the control. The results 1) support the previously hypothesized hormonal network in the immune system, 2) justify that the insulin effect is not species dependent and 3) call attention to the sex, species and organ differences in the response.

  2. ACTH-secreting 'apudoma' of gallbladder.

    PubMed Central

    Spence, R W; Burns-Cox, C J

    1975-01-01

    The case of a 44-year-old woman is reported. The diagnosis after the appropriate tests and laparotomy was ACTH-secreting 'apudoma' of the gallbladder. This is a rare tumour and this case is believed to be the first reported of an ectopic hormone producing tumour from this side. Images Fig 1 Fig 2 PMID:168130

  3. Habituation of hypothalamic-pituitary-adrenocortical axis hormones to repeated homotypic stress and subsequent heterotypic stressor exposure in male and female rats.

    PubMed

    Babb, Jessica A; Masini, Cher V; Day, Heidi E W; Campeau, Serge

    2014-05-01

    Understanding potential sex differences in repeated stress-induced hypothalamic-pituitary-adrenocortical (HPA) axis habituation could provide insight into the sex-biased prevalence of certain affective disorders such as anxiety and depression. Therefore in these studies, male and female rats were exposed to 30 min of either audiogenic or restraint stress daily for 10 days in order to determine whether sex regulates the extent to which HPA axis hormone release is attenuated upon repeated homotypic stressor presentation. In response to the initial exposure, both stressors robustly increased plasma concentrations of both adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in both sexes. Acutely, females displayed higher ACTH and CORT concentrations following restraint stress, whereas males exhibited higher hormone concentrations following loud noise stress. HPA axis hormone responses to both stressors decreased incrementally over successive days of exposure to each respective stressor. Despite the differential effect of sex on acute hormone responses, the extent to which HPA axis hormone response was attenuated did not differ between male and female animals following either stressor. Furthermore, ACTH and CORT responses to a novel environment were not affected by prior exposure to stress of either modality in either male or female rats. These experiments demonstrate that despite the acute stress response, male and female rats exhibit similar habituation of HPA axis hormones upon repeated homotypic stressor presentations, and that exposure to repeated stress does not produce exaggerated HPA axis hormone responses to a novel environment in either female or male rats.

  4. The role of inferior petrosal sinus sampling in ACTH-dependent Cushing's syndrome: review and joint opinion statement by members of the Italian Society for Endocrinology, Italian Society for Neurosurgery, and Italian Society for Neuroradiology.

    PubMed

    Pecori Giraldi, Francesca; Cavallo, Luigi Maria; Tortora, Fabio; Pivonello, Rosario; Colao, Annamaria; Cappabianca, Paolo; Mantero, Franco

    2015-02-01

    In the management of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, inferior petrosal sinus sampling (IPSS) provides information for the endocrinologist, the neurosurgeon, and the neuroradiologist. To the endocrinologist who performs the etiological diagnosis, results of IPSS confirm or exclude the diagnosis of Cushing's disease with 80%-100% sensitivity and over 95% specificity. Baseline central-peripheral gradients have suboptimal accuracy, and stimulation with corticotropin-releasing hormone (CRH), possibly desmopressin, has to be performed. The rationale for the use of IPSS in this context depends on other diagnostic means, taking availability of CRH and reliability of dynamic testing and pituitary imaging into account. As regards the other specialists, the neuroradiologist may collate results of IPSS with findings at imaging, while IPSS may prove useful to the neurosurgeon to chart a surgical course. The present review illustrates the current standpoint of these 3 specialists on the role of IPSS.

  5. Effects of ACTH and cAMP on steroidogenic acute regulatory protein and P450 11beta-hydroxylase messenger RNAs in rainbow trout interrenal cells: relationship with in vitro cortisol production.

    PubMed

    Hagen, I Julie; Kusakabe, Makoto; Young, Graham

    2006-02-01

    Steroidogenic acute regulatory protein (StAR) transfers cholesterol over the inner mitochondrial membrane, thereby making the molecule available for cholesterol side-chain cleavage enzyme, which carries out the first conversion in the steroidogenic pathway. In mammals, StAR controls this rate limiting step in steroidogenesis, and both StAR protein and StAR mRNA levels become rapidly elevated in response to tropic hormone stimulation. The relationship between StAR gene expression and steroid production in fish has not yet been well explored. We investigated the relationship between adrenocorticotropic hormone (ACTH)- and cAMP-stimulated cortisol production in vitro and levels of StAR transcripts in interrenal cells of rainbow trout. To assess the effect of ACTH on mRNA levels of a downstream steroidogenic enzyme, we also investigated the effects of ACTH on transcripts encoding 11beta hydroxylase (P450 11beta). In a series of experiments, juvenile rainbow trout head kidney tissue containing interrenal cells was incubated with either ACTH or dibutyryl cyclic AMP (dbcAMP). Cortisol in incubation media were measured by radioimmunoassay and total RNA was isolated from the tissue for Northern analysis or for quantitative real-time PCR. Incubation of tissue with 150 ng/mL ACTH for 1-18 h induced a progressive increase in cortisol accumulation in media, but StAR mRNA levels increased modestly and mostly insignificantly over 18 h, irrespective of treatment. Exposure of tissue for 18 h to 5, 150, 500 or 1,500 ng ACTH/mL resulted in a strong increase in cortisol production, with a peak response (15-fold increase over controls) achieved with 150 ng/mL ACTH. Although there was a trend towards a dose-response effect, mean StAR mRNA levels were only significantly affected by the highest concentration of ACTH used (1,500 ng/mL), which induced a less than 2-fold increase in StAR transcripts. However, there was a significant linear relationship between StAR mRNA levels and ACTH

  6. Chronic Hormonal Imbalance and Adipose Redistribution Is Associated with Hypothalamic Neuropathology following Blast Exposure.

    PubMed

    VandeVord, Pamela J; Sajja, Venkata Siva Sai Sujith; Ereifej, Evon; Hermundstad, Amy; Mao, Shijie; Hadden, Timothy J

    2016-01-01

    Endocrine disorders have been shown to be a consequence of blast traumatic brain injury in soldiers returning from military conflicts. Hormone deficiency and adrenocorticotropic hormone (ACTH) dysfunction can lead to symptoms such as fatigue, anxiety, irritability, insomnia, sexual dysfunction, and decreased quality of life. Given these changes following blast exposure, the current study focused on investigating chronic pathology within the hypothalamus following blast, in addition to systemic effects. An established rodent model of blast neurotrauma was used to induce mild blast-induced neurotrauma. Adipose tissue, blood, and brain samples were collected at one and three months following a single blast exposure. Adipose tissue and blood were evaluated for changes in ACTH, adiponectin, C-reactive protein, glial fibrillary acidic protein, interleukin (IL)-1β, and leptin. The hypothalamus was evaluated for injury using immunohistochemical techniques. The results demonstrated that the weight of the blast animals was significantly less, compared with the sham group. The slower rate of increase in their weight was associated with changes in ACTH, IL-1β, and leptin levels. Further, histological analysis indicated elevated levels of cleaved caspase-3 positive cells within the hypothalamus. The data suggest that long-term outcomes of brain injury occurring from blast exposure include dysfunction of the hypothalamus, which leads to compromised hormonal function, elevated biological stress-related hormones, and subsequent adipose tissue remodeling.

  7. Chronic Hormonal Imbalance and Adipose Redistribution Is Associated with Hypothalamic Neuropathology following Blast Exposure

    PubMed Central

    Sajja, Venkata Siva Sai Sujith; Ereifej, Evon; Hermundstad, Amy; Mao, Shijie; Hadden, Timothy J.

    2016-01-01

    Abstract Endocrine disorders have been shown to be a consequence of blast traumatic brain injury in soldiers returning from military conflicts. Hormone deficiency and adrenocorticotropic hormone (ACTH) dysfunction can lead to symptoms such as fatigue, anxiety, irritability, insomnia, sexual dysfunction, and decreased quality of life. Given these changes following blast exposure, the current study focused on investigating chronic pathology within the hypothalamus following blast, in addition to systemic effects. An established rodent model of blast neurotrauma was used to induce mild blast-induced neurotrauma. Adipose tissue, blood, and brain samples were collected at one and three months following a single blast exposure. Adipose tissue and blood were evaluated for changes in ACTH, adiponectin, C-reactive protein, glial fibrillary acidic protein, interleukin (IL)-1β, and leptin. The hypothalamus was evaluated for injury using immunohistochemical techniques. The results demonstrated that the weight of the blast animals was significantly less, compared with the sham group. The slower rate of increase in their weight was associated with changes in ACTH, IL-1β, and leptin levels. Further, histological analysis indicated elevated levels of cleaved caspase-3 positive cells within the hypothalamus. The data suggest that long-term outcomes of brain injury occurring from blast exposure include dysfunction of the hypothalamus, which leads to compromised hormonal function, elevated biological stress-related hormones, and subsequent adipose tissue remodeling. PMID:26274838

  8. Hormonal and Behavioral Responses to Stress in Lactating and Non-lactating Female Common Marmosets (Callithrix jacchus)

    PubMed Central

    Saltzman, Wendy; Abbott, David H.

    2011-01-01

    In several mammalian species, hypothalamic-pituitary-adrenal (HPA) and behavioral responses to stressors are down-regulated in lactating females, possibly preventing stress-induced disruptions of maternal care. Experimental elevations of HPA axis hormones have been found to inhibit maternal behavior in lactating common marmoset monkeys (Callithrix jacchus), raising the question of whether lactating female marmosets also have blunted endogenous responses to stress. Therefore, we compared HPA and behavioral responses to standardized stressors in reproductively experienced female common marmosets that were undergoing ovulatory cycles and that either were (N=7) or were not lactating (N=8). Each marmoset underwent (1) a restraint stressor during the early follicular phase of the ovarian cycle (approximately 5 weeks postpartum for lactating females) and (2) exposure to a simulated hawk predator during the early to mid-luteal phase (approximately 7 weeks postpartum for lactating females). Lactating females were tested in the presence of one of their infants. Blood samples were collected before, during, and immediately after each test for determination of plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations. Both stressors caused significant elevations in plasma ACTH and cortisol levels, and significant decreases in cortisol:ACTH ratios; however, lactating and non-lactating females showed no significant differences in their endocrine or behavioral responses to either stressor, or in baseline ACTH or cortisol levels. These findings suggest that in contrast to several other mammalian species, lactating female marmosets maintain full behavioral and HPA responsiveness to stress, at least in the presence of their infants. PMID:21600906

  9. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland.

    PubMed

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-04-25

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and Sox9(+) adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors.

  10. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland

    PubMed Central

    Pyczek, Joanna; Buslei, Rolf; Schult, David; Hölsken, Annett; Buchfelder, Michael; Heß, Ina; Hahn, Heidi; Uhmann, Anja

    2016-01-01

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2+ and Sox9+ adult pituitary stem cells and to elevated expression levels of adrenocorticotropic hormone (Acth), growth hormone (Gh) and prolactin (Prl) in the adult gland. Inhibition of the pathway by cyclopamine reversed these effects indicating that active Hh signaling positively regulates proliferative processes of adult pituitary stem cells and hormone production in the anterior pituitary. Since hormone producing cells of the adenohypophysis as well as ACTH-, GH- and PRL-immunopositive adenomas express SHH and its target GLI1, we furthermore propose that excess HH signaling is involved in the development/maintenance of hormone-producing pituitary adenomas. These findings advance the understanding of physiological hormone regulation and may open new treatment options for pituitary tumors. PMID:27109116

  11. Central neuropeptide B administration activates stress hormone secretion and stimulates feeding in male rats.

    PubMed

    Samson, W K; Baker, J R; Samson, C K; Samson, H W; Taylor, M M

    2004-10-01

    Neuropeptide B (NPB) was identified to be an endogenous, peptide ligand for the orphan receptors GPR7 and GPR8. Because GPR7 is expressed in rat brain and, in particular, in the hypothalamus, we hypothesized that NPB might interact with neuroendocrine systems that control hormone release from the anterior pituitary gland. No significant effects of NPB were observed on the in vitro releases of prolactin, adrenocorticotropic hormone (ACTH) or growth hormone (GH) when log molar concentrations ranging from 1 pM to 100 nM NPB were incubated with dispersed anterior pituitary cells harvested from male rats. In addition NPB (100 nM) did not alter the concentration response stimulation of prolactin secretion by thyrotropin-releasing hormone, ACTH secretion by corticotropin-releasing factor (CRF) and GH secretion by GH-releasing hormone. However, NPB, when injected into the lateral cerebroventricle (i.c.v.) of conscious, unrestrained male rats, elevated prolactin and corticosterone, and lowered GH levels in circulation. The threshold dose for the effect on corticosterone and prolactin levels was 1.0 nmol, while that for the effect on GH release was 3.0 nmol NPB. Pretreatment with a polyclonal anti-CRF antiserum completely blocked the ability of NPB to stimulate ACTH release and significantly inhibited the effect of NPB on plasma corticosterone levels. NPB administration i.c.v. did not significantly alter plasma vasopressin and oxytocin levels in conscious rats. It did stimulate feeding (minimum effective dose 1.0 nmol) in sated animals in a manner similar to that of the other endogenous ligand for GPR7, neuropeptide W. We conclude that NPB can act in the brain to modulate neuroendocrine signals accessing the anterior pituitary gland, but does not itself act as a releasing or inhibiting factor in the gland, at least with regard to prolactin, ACTH and GH secretion.

  12. Ectopic ACTH-secreting pituitary adenoma of the sphenoid sinus: case report of endoscopic endonasal resection and systematic review of the literature.

    PubMed

    Seltzer, Justin; Lucas, Joshua; Commins, Deborah; Lerner, Olga; Lerner, Alexander; Carmichael, John D; Zada, Gabriel

    2015-02-01

    Ectopic pituitary adenomas are exceedingly rare entities that are often misdiagnosed. The resulting delay in diagnosis may be particularly concerning in the case of Cushing syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Although the total resection of ectopic adenomas results in rapid and durable remission, persistent Cushing syndrome is often associated with permanently damaging invasive procedures and significantly higher risk of mortality. The authors report the case of a 48-year-old man with ACTH-dependent Cushing syndrome. On the morning before surgery, his serum cortisol measured 51 μg/dl, his ACTH level was 195.7 pg/ml, and his urinary free cortisol level was 2109 μg/day. Serum cortisol was not suppressed with the administration of high-dose dexamethasone. Imaging showed separate masses in both the sphenoid sinus and the pituitary gland, complicating the diagnostic process and requiring pathological assessment of both masses. No other abnormalities were found on thoracic, abdominal, or pelvic scans. Gross-total resection of both lesions was accomplished via an endoscopic endonasal transsphenoidal approach. Pathology confirmed an ectopic ACTH pituitary adenoma of the sphenoid sinus and a Crooke hyaline change of the pituitary gland. The patient achieved stable hormonal remission without significant postoperative complications, returned to full activity within 3 months, and remained disease free nearly 1 year after tumor resection. In a systematic literature review, the authors identified 41 cases of ectopic ACTH-secreting pituitary adenomas, including 18 arising in the sphenoid sinus without direct involvement of the sella. Including the case described here, the total number of ectopic ACTH pituitary adenomas arising in the sphenoid sinus was 19, and the total number of ectopic ACTH pituitary adenomas without regard to location was 42. For the 19 patients with adenomas found in the sphenoid sinus, ages ranged

  13. Hypothalamic-pituitary-adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones.

    PubMed

    Stephens, Mary Ann C; Mahon, Pamela B; McCaul, Mary E; Wand, Gary S

    2016-04-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to the

  14. Esthesioneuroblastoma (Olfactory Neuroblastoma) with Ectopic ACTH Syndrome: a multidisciplinary case presentation from the Joan Karnell cancer center of Pennsylvania Hospital.

    PubMed

    Mintzer, David M; Zheng, Sarah; Nagamine, Michiko; Newman, Jason; Benito, Maria

    2010-01-01

    The case of a patient with recurrent esthesioneuroblastoma complicated by ectopic adrenocorticotropic hormone production is presented, including the workup and management of this uncommon complication of an uncommon disease.

  15. The effects of ACTH on steroid metabolomic profiles in human adrenal cells.

    PubMed

    Xing, Yewei; Edwards, Michael A; Ahlem, Clarence; Kennedy, Mike; Cohen, Anthony; Gomez-Sanchez, Celso E; Rainey, William E

    2011-06-01

    The adrenal glands are the primary source of mineralocorticoids, glucocorticoids, and the so-called adrenal androgens. Under physiological conditions, cortisol and adrenal androgen synthesis are controlled primarily by ACTH. Although it is well established that ACTH can stimulate steroidogenesis in the human adrenal gland, the effect of ACTH on overall production of different classes of steroid hormones has not been defined. In this study, we examined the effect of ACTH on the production of 23 steroid hormones in adult adrenal primary cultures and 20 steroids in the adrenal cell line, H295R. Liquid chromatography/tandem mass spectrometry analysis revealed that, in primary adrenal cell cultures, cortisol and corticosterone were the two most abundant steroid hormones produced with or without ACTH treatment (48  h). Cortisol production responded the most to ACTH treatment, with a 64-fold increase. Interestingly, the production of two androgens, androstenedione and 11β-hydroxyandrostenedione (11OHA), that were also produced in large amounts under basal conditions significantly increased after ACTH incubation. In H295R cells, 11-deoxycortisol and androstenedione were the major products under basal conditions. Treatment with forskolin increased the percentage of 11β-hydroxylated products, including cortisol and 11OHA. This study illustrates that adrenal cells respond to ACTH through the secretion of a variety of steroid hormones, thus supporting the role of adrenal cells as a source of both corticosteroids and androgens.

  16. Validating the Novel Method of Measuring Cortisol Levels in Cetacean Skin by Use of an ACTH Challenge in Bottlenose Dolphins

    DTIC Science & Technology

    2013-09-30

    known as an ACTH (adrenocorticotrophic hormone ) challenge, in a group of bottlenose dolphins (Tursiops truncatus). The dolphins will be sampled as part...of an ongoing study of stress hormones conducted by Dr. Dorian Houser in collaboration with the U.S. Navy Marine Mammal Program (MMP). The ACTH

  17. Naloxone inhibits and morphine potentiates. The adrenal steroidogenic response to ACTH

    NASA Technical Reports Server (NTRS)

    Heybach, J. P.; Vernikos, J.

    1980-01-01

    The adrenal actions were stereospecific since neither the positve stereoisomer of morphine, nor that of naloxone, had any effect on the adrenal response to exogenous adrenocorticotrophic hormone (ACTH). The administration of human beta endorphin to phyophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone secreting cells of the adrenal cortex.

  18. ACTH Action on StAR Biology.

    PubMed

    Clark, Barbara J

    2016-01-01

    Adrenocorticotropin hormone (ACTH) produced by the anterior pituitary stimulates glucocorticoid synthesis by the adrenal cortex. The first step in glucocorticoid synthesis is the delivery of cholesterol to the mitochondrial matrix where the first enzymatic reaction in the steroid hormone biosynthetic pathway occurs. A key response of adrenal cells to ACTH is activation of the cAMP-protein kinase A (PKA) signaling pathway. PKA activation results in an acute increase in expression and function of the Steroidogenic Acute Regulatory protein (StAR). StAR plays an essential role in steroidogenesis- it controls the hormone-dependent movement of cholesterol across the mitochondrial membranes. Currently StAR's mechanism of action remains a major unanswered question in the field. However, some insight may be gained from understanding the mechanism(s) controlling the PKA-dependent phosphorylation of StAR at S194/195 (mouse/human StAR), a modification that is required for function. This mini-review provides a background on StAR's biology with a focus on StAR phosphorylation. The model for StAR translation and phosphorylation at the outer mitochondrial membrane, the location for StAR function, is presented to highlight a unifying theme emerging from diverse studies.

  19. ACTH Action on StAR Biology

    PubMed Central

    Clark, Barbara J.

    2016-01-01

    Adrenocorticotropin hormone (ACTH) produced by the anterior pituitary stimulates glucocorticoid synthesis by the adrenal cortex. The first step in glucocorticoid synthesis is the delivery of cholesterol to the mitochondrial matrix where the first enzymatic reaction in the steroid hormone biosynthetic pathway occurs. A key response of adrenal cells to ACTH is activation of the cAMP-protein kinase A (PKA) signaling pathway. PKA activation results in an acute increase in expression and function of the Steroidogenic Acute Regulatory protein (StAR). StAR plays an essential role in steroidogenesis- it controls the hormone-dependent movement of cholesterol across the mitochondrial membranes. Currently StAR's mechanism of action remains a major unanswered question in the field. However, some insight may be gained from understanding the mechanism(s) controlling the PKA-dependent phosphorylation of StAR at S194/195 (mouse/human StAR), a modification that is required for function. This mini-review provides a background on StAR's biology with a focus on StAR phosphorylation. The model for StAR translation and phosphorylation at the outer mitochondrial membrane, the location for StAR function, is presented to highlight a unifying theme emerging from diverse studies. PMID:27999527

  20. Non-invasive monitoring of stress hormones in the bat Eptesicus isabellinus - Do fecal glucocorticoid metabolite concentrations correlate with survival?

    PubMed

    Kelm, Detlev H; Popa-Lisseanu, Ana G; Dehnhard, Martin; Ibáñez, Carlos

    2016-01-15

    Chronic stress may negatively impact fitness and survival in wildlife. Stress hormone analysis from feces is a non-invasive tool for identifying stressors and deducing about individual and population level fitness. Although many bat populations are endangered, fecal stress hormone analysis has not been established in bats as a method for focusing conservation efforts. The isabelline serotine bat, Eptesicus isabellinus, is exposed to human disturbance as its roosts are mostly found in anthropogenic structures. Moreover, this bat is host to various diseases and survival rates between colonies may vary significantly. To validate the analysis of fecal glucocorticoid metabolites, we applied an adrenocorticotropic hormone (ACTH) challenge and tested four different enzyme immunoassays (EIA) for measuring glucocorticoid concentrations. Cortisol and its metabolites showed the highest increase in blood and feces after the ACTH challenge, but corticosterone and its metabolites also increased significantly. Baseline fecal cortisol metabolite (FCM) concentrations did not increase until 1.5h after the animals were captured, which is a convenient time lag for sample collection from captured animals. We furthermore compared baseline FCM concentrations between five colonies of E. isabellinus in Andalusia, Spain, and tested for their correlation with survival rates. FCM concentrations did not vary between colonies, but FCM levels increased with the animals' age. FCM analysis may prove a useful tool for identifying bat colonies that experience uncommon environmental stress. However, inter-individual variation in hormone secretion, due to factors such as age, may require additional information to properly interpret differences in hormone concentrations.

  1. [The development of adrenal cortical hormones into drugs].

    PubMed

    Hansen, Sven Erik

    2008-01-01

    The interplay of factors contributing to the development of adrenal cortical hormones into drugs is reviewed. Clinical research performed during long periods by the physicians T. Addison and P.S. Hench in a nearly obsessional way stimulated basic research in physiology and biochemistry of the adrenal glands. From about 1900 increasing public interest in the "new hormones"coincided with expansion in research and development in academic and industrial settings. Pharmaceutical companies developed skill by production of much demanded organ-extracts, both effective ones as insulin and preparations of questionable clinical value. In 1949 the powerful anti-inflammatory effect of the cortical hormone, cortisone was discovered. As the supply of that hormone was scanty, it had temporarily to be substituted by the adrenocorticotropic hormone (ACTH) from animal hypophyses. Thereafter development accelerated through the combined effect of many years' painstaking research on the adrenal cortical hormones, technological breakthroughs, a climate positive for bold clinical experimentation and vigorous competition among mainly American pharmaceutical companies. Within a decade prednisone, the successor of cortisone, was launched, its clinical use established and large-scale inexpensive production instituted.

  2. Glucoreceptors located in different areas mediate the hypoglycemia-induced release of growth hormone, prolactin, and adrenocorticotropin in man.

    PubMed

    Vigas, M; Tatár, P; Jurcovicová, J; Jezová, D

    1990-03-01

    In young male volunteers, the changes in growth hormone (GH), prolactin (PRL), and adrenocorticotropic hormone (ACTH) release in response to insulin injection combined with the infusion of saline, glucose, and fructose were evaluated. Glucose infusion in a dose which prevented insulin hypoglycemia completely abolished endocrine responses. Infusion of fructose, which is known not to cross the blood-brain barrier (BBB), did not influence the GH release during hypoglycemia; however, it inhibited PRL secretion. The ACTH response was slightly attenuated and delayed, while the hypoglycemia-induced rise in cortisol levels was not modified by fructose infusion. These data indicate that the glucoreceptors mediating the signals for a complete counterregulatory neuroendocrine response are not located in a single brain structure. Stimuli for GH release are produced in areas of the central nervous system protected by the BBB, while those for PRL release are presumably present in structures not protected by the BBB. Glucoreceptors triggering ACTH release are located both inside and outside the BBB.

  3. The effects of physical therapeutic agents on serum levels of stress hormones in patients with osteoarthritis

    PubMed Central

    Tönük, Şükrü Burak; Serin, Erdinc; Ayhan, Fikriye Figen; Yorgancioglu, Zeynep Rezan

    2016-01-01

    Abstract To investigate the effects of physical agents on the levels of stress hormones in patients with osteoarthritis (OA). Transcutaneous electrical nerve stimulation, hot packs, and therapeutic ultrasound were applied to the lumbar region and knees of patients with OA. Blood samples were taken for the measurement of the serum levels of glucose, insulin (INS), growth hormone (GH), prolactin (PRL), cortisol (COR), and plasma adrenocorticotropic hormone (ACTH) immediately before and after the 1st session, to investigate the acute effects of those physical agents on the endocrine system. The hormone levels were also measured every 5 sessions in a total of 10 sessions. The treatment response was also evaluated by using the visual analogue scale (VAS), Roland Morris Disability Questionnaire (RMDQ), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) throughout the therapy period. After the 1st session, there was a decrease in INS levels and a mild decrease in PRL levels (P = 0.001 and P < 0.05, respectively). Throughout the 10-session therapy period, the INS levels increased, whereas the ACTH and COR levels decreased (P < 0.05 for all). The VAS-spine, RMDQ, VAS-knee, and WOMAC scores decreased (P = 0.001 for VAS-spine and P < 0.001 for all others). A positive correlation was detected between the changes in serum COR and WOMAC-pain score (P < 0.05). Although the combination therapy caused changes in INS level accompanied with steady glucose levels, the application of physical agents did not adversely affect the hormone levels. The decrease in ACTH and COR levels may be attributed to the analgesic effect of agents and may be an indicator of patient comfort through a central action. PMID:27583888

  4. Isolation of ACTH-resistant Y1 adrenal tumor cells

    SciTech Connect

    Schimmer, B.P.

    1985-01-01

    Y1 cells originate from a minimally deviated mouse adrenal tumor. When treated with ACTh or cAMP, these cells increase the rate of steroiodigenesis, stop dividing, assume a rounded morphology, and detach from the culture vessel. The ability of ACTH and cAMP to inhibit Y1 cell growth and cause cell rounding and detachment provides a basis for selection of Y1 mutants resistant to hormones and cyclic nucleotides. Newly cloned populations of Y1 cells can be treated with mutagens, such as N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) or ethyl methanesulfonate (EMS) to raise the frequency of specific mutations to detectable levels.

  5. Circadian variation in ghrelin and certain stress hormones in crib-biting horses.

    PubMed

    Hemmann, Karin; Raekallio, Marja; Kanerva, Kira; Hänninen, Laura; Pastell, Matti; Palviainen, Mari; Vainio, Outi

    2012-07-01

    Crib-biting is classified as an oral stereotypy, which may be initiated by stress susceptibility, management factors, genetic factors and gastrointestinal irritation. Ghrelin has been identified in the gastric mucosa and is involved in the control of food intake and reward, but its relationship to crib-biting is not yet known. The aim of this study was to examine the concentration and circadian variation of plasma ghrelin, cortisol, adrenocorticotropic hormone (ACTH) and β-endorphin in crib-biting horses and non-crib-biting controls. Plasma samples were collected every second hour for 24h in the daily environment of eight horses with stereotypic crib-biting and eight non-crib-biting controls. The crib-biting horses had significantly higher mean plasma ghrelin concentrations than the control horses. The circadian rhythm of cortisol was evident, indicating that the sampling protocol did not inhibit the circadian regulation in these horses. Crib-biting had no statistically significant effect on cortisol, ACTH or β-endorphin concentrations. The inter-individual variations in β-endorphin and ACTH were higher than the intra-individual differences, which made inter-individual comparisons difficult and complicated the interpretation of results. Further research is therefore needed to determine the relationship between crib-biting and ghrelin concentration.

  6. Effects of electromagnetic radiation exposure on stress-related behaviors and stress hormones in male wistar rats.

    PubMed

    Mahdavi, Seyed Mohammad; Sahraei, Hedayat; Yaghmaei, Parichehreh; Tavakoli, Hassan

    2014-11-01

    Studies have demonstrated that electromagnetic waves, as the one of the most important physical factors, may alter cognitive and non-cognitive behaviors, depending on the frequency and energy. Moreover, non-ionizing radiation of low energy waves e.g. very low frequency waves could alter this phenomenon via alterations in neurotransmitters and neurohormones. In this study, short, medium, and long-term exposure to the extremely low frequency electromagnetic field (ELF-EMF) (1 and 5 Hz radiation) on behavioral, hormonal, and metabolic changes in male Wistar rats (250 g) were studied. In addition, changes in plasma concentrations for two main stress hormones, noradrenaline and adrenocorticotropic hormone (ACTH) were evaluated. ELF-EMF exposure did not alter body weight, and food and water intake. Plasma glucose level was increased and decreased in the groups which exposed to the 5 and 1Hz wave, respectively. Plasma ACTH concentration increased in both using frequencies, whereas nor-adrenaline concentration showed overall reduction. At last, numbers of rearing, sniffing, locomotor activity was increased in group receiving 5 Hz wave over the time. In conclusions, these data showed that the effects of 1 and 5 Hz on the hormonal, metabolic and stress-like behaviors may be different. Moreover, the influence of waves on stress system is depending on time of exposure.

  7. Serotonin transporter genotype modulates HPA axis output during stress: effect of stress, dexamethasone test and ACTH challenge

    PubMed Central

    Sorenson, Andrea N.; Sullivan, Erin C.; Mendoza, Sally P.; Capitanio, John P.; Higley, J. Dee

    2014-01-01

    Background Studies show that the hypothalamic–pituitary–adrenal (HPA) axis is dysregulated in depression. Some studies suggest that variation in the serotonin transporter genotype (hereafter 5HTT) modulates both risk for depression and psychopathological HPA axis responsiveness. Rhesus monkeys are well suited to model such relationships. Rhesus macaque models of human psychopathology have assessed the effect of the serotonin transporter (rh5HTT) on levels of cortisol in stressed subjects. These studies show that that under conditions of stress, heterozygous females (Ls) reared under adversity exhibit high levels of cortisol. Studies have not to our knowledge, however, assessed the potential additive effect on the cortisol response in a number of macaque subjects homozygous for the serotonin transporter short allele (ss). Moreover, little is known about the level of the central or peripheral nervous system at which the 5HTT genotype acts to modulate the cortisol response. Methods This study assesses a relatively large number of subjects homozygous and heterozygous for the rh5HTT short and long alleles (a) during stress; (b) following a dexamethasone suppression test; and (c) following an adrenocorticotropic hormone (ACTH) challenge. Subjects included 190 infant rhesus macaques (Macaca mulatta – 84 males and 106 females; 118 LL, 60 Ls, and 12 ss subjects), obtaining two blood plasma samples during the stress of separation from their mothers. Then on the following day, we obtained a blood sample following a dexamethasone test, and later that day we obtained a blood sample after an ACTH challenge test. Subjects ranged in age between 90 and 128 days, with a mean age of 107 days. Results Subjects homozygous for the short allele had significantly higher levels of cortisol across all test conditions, when compared to those homozygous for the long allele, or those heterozygous with Ls alleles. Subsequent analyses showed a high correlation between individual cortisol

  8. Ectopic ACTH syndrome: clinicopathological correlations.

    PubMed Central

    Singer, W; Kovacs, K; Ryan, N; Horvath, E

    1978-01-01

    Ten out of 164 cases of bronchogenic carcinoma showed pathological evidence at necropsy of the ectopic ACTH syndrome. All occurred in association with oat-cell carcinoma, constituting 19% of that group. The pathological features consisted of adrenocortical hyperplasia confined to the zona fasciculata and Crooke's hyaline change in the pituitary. Immunoperoxidase stainable ACTH was detected in the pituitary but not in the carcinoma tissue, a surprising finding, which may be due to the different nature of ACTH present in tumour tissue. The ectopic ACTH syndrome was diagnosed ante mortem in only four out of 10 patients on the basis of hypokalaemia and metabolic alkalosis. The lack of clinical pointers in all but terminal cases is discussed as well as possible measures for earlier diagnosis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:209063

  9. Mapping the human corticotropin releasing hormone binding protein gene (CRHBP) to the long arm of chromosome 5 (5q11.2-q13.3)

    SciTech Connect

    Vamvakopoulos, N.C.; Sioutopoulou, T.O.; Durkin, S.A.

    1995-01-01

    Unexpected stimulation or stress activates the heat shock protein (hsp) system at the cellular level and the hypothalamic-pituitary-adrenal (HPA) axis at the level of the whole organism. At the molecular level, these two systems communicate through the functional interaction between hsp90 and glucocorticoid receptor (GR). The corticotropin releasing hormone (CRH) system regulates the mammalian stress response by coordinating the activity of the HPA axis. It consists of the 41-amino-acid-long principal hypothalamic secretagogue for pituitary adrenocorticotropic hormone (ACTH), CRH, its receptor (CRHR), and its binding protein (CRHBP). Because of its central role in the coordination of stress response and whole body homeostasis, the CRH system has been implicated in the pathogenesis of neuroendocrine and psychiatric disease. 19 refs., 1 fig.

  10. Ketamine Inhibits Fetal ACTH Responses to Cerebral Hypoperfusion

    PubMed Central

    Powers, Melanie J.; Wood, Charles E.

    2009-01-01

    The present study tested the effect of ketamine on the fetal reflex responses of late-gestation sheep to brachiocephalic occlusion (BCO), a stimulus that mimics the reduction in cerebral blood flow that results from severe fetal hypotension. Ketamine, a dissociative anesthetic and known non-competitive antagonist of N-methyl D-aspartate (NMDA) receptors, has previously been shown to impair chemoreceptor responsiveness. Studies from this laboratory suggest that fetal reflex ACTH responses to hypotension are largely mediated by chemoreceptors; therefore we hypothesized that ketamine would inhibit the reflex hormonal response to BCO. Chronically catheterized fetal sheep were subjected to acute cerebral hypoperfusion through occlusion of the brachiocephalic artery. Fetal blood pressure and heart rate were continuously recorded and fetal blood samples drawn during the experiment were analyzed with specific hormone assays. Our results demonstrate that ketamine attenuates hemodynamic responses to cerebral hypoperfusion and is a potent inhibitor of adrenocorticotropin (ACTH) and proopiomelanocortin (POMC) / pro-ACTH release. These data support the hypothesis that fetal reflex responses hypotension are chemoreceptor mediated. Given the potency with which ketamine inhibits ACTH response to fetal hypotension, we suggest that the use of ketamine, or other anesthetic or analgesic drugs that block or otherwise interact with the NMDA-glutamate pathways, in late pregnancy or in pre-term newborns be reconsidered. PMID:17158270

  11. Effect of salinity changes on olfactory memory-related genes and hormones in adult chum salmon Oncorhynchus keta.

    PubMed

    Kim, Na Na; Choi, Young Jae; Lim, Sang-Gu; Jeong, Minhwan; Jin, Deuk-Hee; Choi, Cheol Young

    2015-09-01

    Studies of memory formation have recently concentrated on the possible role of N-methyl-d-aspartate receptors (NRs). We examined changes in the expression of three NRs (NR1, NR2B, and NR2C), olfactory receptor (OR), and adrenocorticotropic hormone (ACTH) in chum salmon Oncorhynchus keta using quantitative polymerase chain reaction (QPCR) during salinity change (seawater→50% seawater→freshwater). NRs were significantly detected in the diencephalon and telencephalon and OR was significantly detected in the olfactory epithelium. The expression of NRs, OR, and ACTH increased after the transition to freshwater. We also determined that treatment with MK-801, an antagonist of NRs, decreased NRs in telencephalon cells. In addition, a reduction in salinity was associated with increased levels of dopamine, ACTH, and cortisol (in vivo). Reductions in salinity evidently caused NRs and OR to increase the expression of cortisol and dopamine. We concluded that memory capacity and olfactory imprinting of salmon is related to the salinity of the environment during the migration to spawning sites. Furthermore, salinity affects the memory/imprinting and olfactory abilities, and cortisol and dopamine is also related with olfactory-related memories during migration.

  12. The effect of stress and stress hormones on dynamic colour-change in a sexually dichromatic Australian frog.

    PubMed

    Kindermann, Christina; Narayan, Edward J; Wild, Francis; Wild, Clyde H; Hero, Jean-Marc

    2013-06-01

    Rapid colour changes in vertebrates have fascinated biologists for centuries, herein we demonstrate dynamic colour change in an anuran amphibian, the stony creek frog (Litoria wilcoxii), which turns from brown to bright (lemon) yellow during amplexus. We show this by comparing the colour of baseline (unpaired males) and amplecting (paired) males. We also investigate the possible role of stress and stress hormones on this colour change. Frogs were subjected to four different levels of stressors (handling, toe-clipping, saline injection and adrenocorticotropic hormone [ACTH] injection) and the colour change was measured using digital photography. A comparison of baseline colour and stress hormone (corticosterone) levels was also conducted to give further insight to this topic. From the images, the Red Blue Green (RGB) colour values were calculated, and a principal components analysis (PCA) was used to create a single colour metric (the major axis) as an index of colour in the visible spectrum. A moderate stressor (toe-clipping) led to a significant change in colour (within 10 min) similar to that of amplecting males. Surprisingly, neither a mild stressor (handling and saline injection) nor the maximum stressor (handling and ACTH injection) led to a lightening response. This study confirms that the dynamic male colour change in this species in response to medium stressors adds new knowledge to the understanding of the functional mechanisms of dynamic colour change in amphibians.

  13. The role of ACTH and glucocorticoids in nonenzymatic fibrinolysis during immobilization stress in animals

    NASA Technical Reports Server (NTRS)

    Kudryashov, B. A.; Shapiro, F. B.; Lomovskaya, E. G.; Lyapina, L. A.

    1980-01-01

    The role of the altered hormonal status of an organism in the activation of the anticoagulative system during stress is investigated. The 30 minute immobilization stress was shown to raise significantly the nonenzymatic fibrinolytic activity of blood in rats. Combined with adrenocorticotropin (ACTH) the effect is still greater. Intravenous administration of 0.2 m1 0.01 percent solution of protamine sulphate prevented the nonenzymatic fibrinolysis induced by the stress. Administration of ACTH after protomine sulphate again raised the fibrinolysis. This suggests that ACTH stimulates the release of heparin.

  14. Melanocortin receptor subtypes in interrenal cells and corticotropic activity of α-melanocyte-stimulating hormones in barfin flounder, Verasper moseri.

    PubMed

    Kobayashi, Yuki; Chiba, Hiroaki; Yamanome, Takeshi; Schiöth, Helgi B; Takahashi, Akiyoshi

    2011-02-01

    The aim of this study was to characterize the pituitary-interrenal axis in barfin flounder, a flatfish. Adrenocorticotropic hormone (ACTH) and melanocortin 2 receptor (MC2R) have been shown to be indispensable substances in pituitary and interrenal cells for cortisol release, respectively. We previously identified ACTH in the pars distalis of the barfin flounder pituitary gland, and detected transcripts of Mc1r, Mc4r, and Mc5r in the head kidney wherein interrenal cells are located. We have now demonstrated the presence of MC2R, which is a specific receptor for ACTH, in interrenal cells by molecular cloning of Mc2r cDNA and in situ hybridization, and confirmation of the in vitro cortisol-releasing activity of ACTH. These results show the presence of a classical pituitary-interrenal axis in this fish. We also evaluated the role of α-melanocyte-stimulating hormone (α-MSH) and its related peptides. In situ hybridization was used to demonstrate the expression of Mc5r in interrenal cells; both desacetyl-α-MSH and diacetyl-α-MSH showed in vitro cortisol-releasing activities, while the activity of α-MSH was negligible. These findings indicate the presence of an additional pituitary-interrenal axis consisting of α-MSH-like peptides secreted from the neurointermediate lobe of the pituitary and MC5R in the interrenal cells. The cortisol-releasing activity of desacetyl-α-MSH and diacetyl-α-MSH, compared with the low activity of α-MSH, suggest a unique and specific functional role of these forms of MSH peptides. The interrenal co-expression of two subtypes of Mcrs may play a role in this specialization.

  15. Semax, an ACTH4-10 peptide analog with high affinity for copper(II) ion and protective ability against metal induced cell toxicity.

    PubMed

    Tabbì, Giovanni; Magrì, Antonio; Giuffrida, Alessandro; Lanza, Valeria; Pappalardo, Giuseppe; Naletova, Irina; Nicoletti, Vincenzo Giuseppe; Attanasio, Francesco; Rizzarelli, Enrico

    2015-01-01

    Heptapeptide Semax, encompassing the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone (ACTH) and a C-terminal Pro-Gly-Pro tripeptide, belongs to a short regulatory peptides family. This compound has been found to affect learning processes and to exert marked neuroprotective activities on cognitive brain functions. Dys-homeostasis of metal ions is involved in several neurodegenerative disorders and growing evidences have showed that brain is a specialized organ able to concentrate metal ions. In this work, the metal binding ability and protective activity of Semax and its metal complexes were studied. The equilibrium study clearly demonstrated the presence of three complex species. Two minor species [CuL] and [CuLH-1]- co-exist together with the [CuLH-2]2- in the pH range from 3.6 to 5. From pH5 the [CuLH-2]2- species becomes predominant with the donor atoms around copper arranged in a 4N planar coordination mode. Noteworthy, a reduced copper induced cytotoxicity was observed in the presence of Semax by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay on a SHSY5Y neuroblastoma and RBE4 endothelial cell lines.

  16. Space weightlessness and hormonal changes in human subjects and experimental animals

    NASA Technical Reports Server (NTRS)

    Grindeland, R. E.

    1982-01-01

    Data from spaceflight and bed rest studies are briefly described and the difficulties in interpreting these results are discussed. Growth hormone, prolactin, adrenocorticotropic hormone, cortisol, insulin, aldosterone, and other hormones are addressed.

  17. The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome.

    PubMed

    de Keyzer, Y; Lenne, F; Auzan, C; Jégou, S; René, P; Vaudry, H; Kuhn, J M; Luton, J P; Clauser, E; Bertagna, X

    1996-03-01

    Ectopic ACTH secretion occurs in highly differentiated and rather indolent tumors like bronchial carcinoids or, in contrast, in various types of aggressive and poorly differentiated neuroendocrine tumors. We explored this phenomenon using the recently cloned human pituitary V3 vasopressin receptor as an alternate molecular marker of the corticotroph phenotype. Expression of V3 receptor, corticotrophin releasing hormone (CRH) receptor, and proopiomelanocortin (POMC) genes was examined in tumors of pituitary and nonpituitary origin. A comparative RT-PCR approach revealed signals for both V3 receptor and CHR receptor mRNAs in 17 of 18 ACTH-secreting pituitary adenomas, and 6 of 6 normal pituitaries; in six growth hormone- or prolactin-secreting adenomas, a very faint V3 receptor signal was observed in three cases, and CRH receptor signal was undetected in all. Six of eight bronchial carcinoids responsible for the ectopic ACTH syndrome had both POMC and V3 receptor signals as high as those in ACTH-secreting pituitary adenomas; in contrast, no POMC signal and only a very faint V3 receptor signal were detected in six of eight nonsecreting bronchial carcinoids. Northern blot analysis showed V3 receptor mRNA of identical size in ACTH-secreting bronchial carcinoids and pituitary tumors. Other types of nonpituitary tumors responsible for ectopic ACTH syndrome presented much lower levels of both POMC and V3 receptor gene expression than those found in ACTH-secreting bronchial carcinoids. In contrast with the V3 receptor, CRH receptor mRNA was detected in the majority of neuroendocrine tumors irrespective of their POMC status. These results show that expression of the V3 receptor gene participates in the corticotroph phenotype. Its striking association with ACTH-secreting bronchial carcinoids defines a subset of nonpituitary tumors in which ectopic POMC gene expression is but one aspect of a wider process of corticotroph cell differentiation, and opens new possibilities of

  18. Cortisol Test

    MedlinePlus

    ... midnight. Cortisol is produced and secreted by the adrenal glands . Production of the hormone is regulated by the ... to produce ACTH (adrenocorticotropic hormone). ACTH stimulates the adrenal glands to produce and release cortisol. In order for ...

  19. Cloning of two melanocortin (MC) receptors in spiny dogfish: MC3 receptor in cartilaginous fish shows high affinity to ACTH-derived peptides while it has lower preference to gamma-MSH.

    PubMed

    Klovins, Janis; Haitina, Tatjana; Ringholm, Aneta; Löwgren, Maja; Fridmanis, Davids; Slaidina, Maija; Stier, Susanne; Schiöth, Helgi B

    2004-11-01

    We report the cloning and characterization of two melanocortin receptors (MCRs) from the spiny dogfish (Squalus acanthias) (Sac). Phylogenetic analysis shows that these shark receptors are orthologues of the MC3R and MC5R subtypes, sharing 65% and 70% overall amino acid identity with the human counterparts, respectively. The SacMC3R was expressed and pharmacologically characterized in HEK293 cells. The radioligand binding results show that this receptor has high affinity for adrenocorticotropic hormone (ACTH)-derived peptides while it has comparable affinity for alpha- and beta-melanocyte stimulating hormone (MSH), and slightly lower affinity for gamma-MSH when compared with the human orthologue. ACTH(1-24) has high potency in a second-messenger cAMP assay while alpha- and gamma-MSH had slightly lower potency in cells expressing the SacMC3R. We used receptor-enhanced green fluorescence protein (EGFP) fusion to show the presence of SacMC3R in plasma membrane of Chinese hamster ovary and HEK293 cells but the SacMC5R was retained in intracellular compartments of these cells hindering pharmacological characterization. The anatomical distribution of the receptors were determined using reverse transcription PCR. The results showed that the SacMC3R is expressed in the hypothalamus, brain stem and telencephalon, optic tectum and olfactory bulbs, but not in the cerebellum of the spiny dogfish while the SacMC5R was found only in the same central regions. This report describes the first molecular characterization of a MC3R in fish. The study indicates that many of the important elements of the MC system existed before radiation of gnathostomes, early in vertebrate evolution, at least 450 million years ago.

  20. Motion sickness susceptibility related to ACTH, ADH and TSH

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.; Leach, C.; Homick, J. L.; Larochelle, F. T.

    1983-01-01

    The hypothesis that endogenous levels of certain hormones might be indicative of an individual's susceptibility to stressful motion is tested in a comparison of subjects classified as less prone to motion sickness with those of higher susceptibility. The levels of ACTH and vasopressin measured before exposure to stressful motion were twice as high in the less-suceptible group. No significant differences were noted in the levels of angiotensin, aldosterone, or TSH. The differences between the two groups were greater for a given hormone than for any of the changes induced by exposure to stressful motion.

  1. Naloxone inhibits and morphine potentiates the adrenal steroidogenic response to ACTH

    NASA Technical Reports Server (NTRS)

    Heybach, J. P.; Vernikos, J.

    1981-01-01

    The administration of morphine to hypophysectomized rats potentiated the steroidogenic response of the adrenal cortex to exogenous adrenocorticotrophic hormone (ACTH) in a dose-dependent fashion. Conversely, the opiate antagonist naloxone inhibited the adrenal response to ACTH. Naloxone pretreatment also antagonized the potentiating effect of morphine on ACTH-induced steroidogenesis in a dose-dependent manner. Neither morphine nor naloxone, administered to hypophysectomized rats, had any direct effect on adrenal steroidogenesis. These adrenal actions were stereospecific since neither the (+)-stereoisomer of morphine, nor that or naloxone, had any effect on the adrenal response to ACTH. The administration of human beta-endorphin to hypophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose-dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone-secreting cells of the adrenal cortex.

  2. Centrifugal acceleration to 3Gz is related to increased release of stress hormones and decreased mood in men and women.

    PubMed

    Schneider, Stefan; Guardiera, Simon; Kleinert, Jens; Steinbacher, Anja; Abel, Thomas; Carnahan, Heather; Strüder, Heiko K

    2008-09-01

    It has been suggested that the central and peripheral neural processes (CPNP) are affected by gravitational changes. Based on the previous experiments during parabolic flights, central and peripheral changes may not only be due to the changed gravitational forces but also due to neuroendocrine reactions related to the psycho-physiological consequences of gravitational changes. The present study focuses on the interaction of neuroendocrine changes and the physical and mental states after acceleration to three-time terrestrial gravity (3Gz). Eleven participants (29.4+/-5.1 [SD] years (male (n=8): 30+/-5.1 years; female (n=3): 27.7+/-2.1 years) underwent a 15 min acceleration to 3Gz in a human centrifuge. Before and after the acceleration to 3Gz circulating stress hormone concentrations (cortisol, adrenocorticotropic hormone (ACTH), prolactin, epinephrine, norepinephrine) and perceived physical and mental states were recorded. A second control group of 11 participants underwent the same testing procedure in a laboratory session. Serum cortisol concentration during exposure to the centrifugal acceleration increased by 70%, plasma concentration of ACTH increased threefold, prolactin twofold, epinephrine by 70% and norepinephrine by 45%, whereas the perceived physical well-being decreased. These findings demonstrate that psycho-physiological changes have to be regarded as a relevant factor for the changes in CPNP during phases of hypergravity exposure.

  3. Aging of the rat adrenocortical cell: response to ACTH and cyclic AMP in vitro.

    PubMed

    Malamed, S; Carsia, R V

    1983-03-01

    To study intrinsic age-related changes in adrenocortical steroid production, cells isolated from rats of different ages (3 to 24 months) were used. Acute (2 hour) corticosterone production in response to stimulation by adrenocorticotrophic hormone (ACTH) and adenosine 3':5'-cyclic monophosphate (cAMP) was measured by radioimmunoassay. With age, adrenocortical cells lose much of their ability to produce corticosterone in the absence or presence of ACTH or cAMP. The loss is progressive from 6 to 24 months of age. Analysis of the data suggests that from 6 to 12 months, an intracellular steroidogenic lesion develops; in addition there may be a loss in ACTH receptors on the plasma membrane. After 12 months these defects increase and are accompanied by a decrease in receptor sensitivity to ACTH.

  4. ACTH TREATMENT OF INFANTILE SPASMS: MECHANISMS OF ITS EFFECTS IN MODULATION OF NEURONAL EXCITABILITY

    PubMed Central

    Brunson, K. L.; Avishai-Eliner, S.; Baram, T. Z.

    2011-01-01

    The efficacy of ACTH, particularly in high doses, for rapid and complete elimination of infantile spasms (IS) has been demonstrated in prospective controlled studies. However, the mechanisms for this efficacy remain unknown. ACTH promotes the release of adrenal steroids (glucocorticoids), and most ACTH effects on the central nervous system have been attributed to activation of glucocorticoid receptors. The manner in which activation of these receptors improves IS and the basis for the enhanced therapeutic effects of ACTH — compared with steroids — for this disorder are the focus of this chapter. First, a possible “common excitatory pathway,” which is consistent with the many etiologies of IS and explains the confinement of this disorder to infancy, is proposed. This notion is based on the fact that all of the entities provoking IS activate the native “stress system” of the brain. This involves increased synthesis and release of the stress-activated neuropeptide, corticotropin-releasing hormone (CRH), in limbic, seizure-prone brain regions. CRH causes severe seizures in developing experimental animals, as well as limbic neuronal injury. Steroids, given as therapy or secreted from the adrenal gland upon treatment with ACTH, decrease the production and release of CRH in certain brain regions. Second, the hypothesis that ACTH directly influences limbic neurons via the recently characterized melanocortin receptors is considered, focusing on the effects of ACTH on the expression of CRH. Experimental data showing that ACTH potently reduces CRH expression in amygdala neurons is presented. This downregulation was not abolished by experimental elimination of steroids or by blocking their receptors and was reproduced by a centrally administered ACTH fragment that does not promote steroid release. Importantly, selective blocking of melanocortin receptors prevented ACTH-induced downregulation of CRH expression, providing direct evidence for the involvement of these

  5. [Neurophysiologic analysis of the effect of ACTH and hydrocortisone on conditioned reflex behavior in cats].

    PubMed

    Sever'ianova, L A

    1977-01-01

    In defensive behaviour of cats, ACTH eliminated extinction delay, evoked by electrical stimulation (with constant parameters) of the midbrain reticular formation, and enhanced the activating influence of the thalamus reticular zone. Hydrocortisone produced opposite effects. In alimentary behaviour, the adaptive hormones enhanced the facilitating effect on extinction, induced by stimulation of non-specific structures and the hypothalamus. However, during hydrocortisone action, encephalographic signs of the reflex remained for a long time after extinction of effector manifestations. Thus, ACTH and hydrocortizone, by changing the interaction between brain structures, exert certain influences on the behavioral processes. The hormonal effects, in turn, depend on the initial co-excitation of the centres.

  6. A Rapid Biochemical and Radiological Response to the Concomitant Therapy with Temozolomide and Radiotherapy in an Aggressive ACTH Pituitary Adenoma.

    PubMed

    Misir Krpan, Ana; Dusek, Tina; Rakusic, Zoran; Solak, Mirsala; Kraljevic, Ivana; Bisof, Vesna; Ozretic, David; Kastelan, Darko

    2017-01-01

    Background and Importance. In the last eight years temozolomide (TMZ) has been used as the last-line treatment modality for aggressive pituitary tumors to be applied after the failure of surgery, medical therapy, and radiotherapy. The objective was to achieve a rapid control of tumor growth and hormone normalization with concurrent chemoradiotherapy in a patient with very aggressive ACTH pituitary adenoma. Clinical Presentation. We describe a patient with an aggressive ACTH-producing adenoma treated with concurrent temozolomide and radiotherapy. The patient suffered from an aggressive ACTH adenoma resistant to surgical and medical treatment. After two months of concurrent temozolomide and radiotherapy, cortisol normalization and significant tumor shrinkage were observed. After 22 months of follow-up, there is still no evidence of tumor recurrence. Conclusion. Concurrent treatment with temozolomide and irradiation appears to be highly effective in the achievement of the tumor volume control as well as in the control of ACTH secretion in aggressive ACTH adenoma.

  7. A Rapid Biochemical and Radiological Response to the Concomitant Therapy with Temozolomide and Radiotherapy in an Aggressive ACTH Pituitary Adenoma

    PubMed Central

    2017-01-01

    Background and Importance. In the last eight years temozolomide (TMZ) has been used as the last-line treatment modality for aggressive pituitary tumors to be applied after the failure of surgery, medical therapy, and radiotherapy. The objective was to achieve a rapid control of tumor growth and hormone normalization with concurrent chemoradiotherapy in a patient with very aggressive ACTH pituitary adenoma. Clinical Presentation. We describe a patient with an aggressive ACTH-producing adenoma treated with concurrent temozolomide and radiotherapy. The patient suffered from an aggressive ACTH adenoma resistant to surgical and medical treatment. After two months of concurrent temozolomide and radiotherapy, cortisol normalization and significant tumor shrinkage were observed. After 22 months of follow-up, there is still no evidence of tumor recurrence. Conclusion. Concurrent treatment with temozolomide and irradiation appears to be highly effective in the achievement of the tumor volume control as well as in the control of ACTH secretion in aggressive ACTH adenoma. PMID:28357143

  8. Coping style and stress hormone responses in genetically heterogeneous rats: comparison with the Roman rat strains.

    PubMed

    Díaz-Morán, Sira; Palència, Marta; Mont-Cardona, Carme; Cañete, Toni; Blázquez, Gloria; Martínez-Membrives, Esther; López-Aumatell, Regina; Tobeña, Adolf; Fernández-Teruel, Alberto

    2012-03-01

    The purpose of the present study was to evaluate for the first time the stress-induced hypothalamus-pituitary-adrenal (HPA), adrenocorticotropic hormone (ACTH), corticosterone and prolactin responses of the National Institutes of Health genetically heterogeneous rat stock (N/Nih-HS rats) in comparison with responses of the relatively high and low stress-prone Roman Low- (RLA-I) and High-Avoidance (RHA-I) rat strains. The same rats were also compared (experiment 1) with respect to their levels of unconditioned anxiety (elevated zero-maze test), novelty-induced exploratory behavior, conditioned fear and two-way active avoidance acquisition. In experiment 2, naive rats from these three strains/stocks were evaluated for "depressive-like" behavior in the forced swimming test. N/Nih-HS and RLA-I rats showed significantly higher post-stress ACTH, corticosterone and prolactin levels than RHA-I rats. N/Nih-HS rats also presented the highest context-conditioned freezing responses, extremely poor two-way avoidance acquisition and very low novelty-induced exploratory behavior. Experiment 2 showed that, compared to RHA-I rats, N/Nih-HS and RLA-I rats displayed significantly less struggling (escape-directed) and increased immobility responses in the forced swimming test. Factor analysis of data from experiment 1 showed associations among behavioral and hormonal responses, with a first factor comprising high loadings of elevated zero-maze variables and lower loadings of conditioned fear, two-way avoidance acquisition and hormonal measures, while a second factor mainly grouped conditioned fear and two-way avoidance acquisition with novelty-induced exploration and post-stress prolactin. Thus, regarding their anxiety/fearfulness, passive coping style, "depressive-like" and stress-induced hormonal responses the N/Nih-HS rats resemble the phenotype profiles of the relatively high-anxious and stress-prone RLA-I rat strain.

  9. Inducible nitric oxide synthase (iNOS) and α-melanocyte-stimulating hormones of iNOS origin play important roles in the allergic reactions of atopic dermatitis in mice.

    PubMed

    Orita, Kumi; Hiramoto, Keiichi; Kobayashi, Hiromi; Ishii, Masamitsu; Sekiyama, Atsuo; Inoue, Masayasu

    2011-11-01

    To elucidate the possible involvement of nitric oxide (NO) derived from inducible NO synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we used an animal model of atopic dermatitis (AD) induced by epicutaneous sensitization and analysed the differences in ear thickness, the frequency of scratching and plasma levels of ovalbumin-specific immunoglobulin E (OVA-IgE), transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, adrenocorticotropic hormone (ACTH) and α-melanocyte-stimulating hormone (α-MSH) between control and iNOS(-/-) mice. Eight-week-old control and iNOS(-/-) male C57BL/6j mice were sensitized three times with OVA antigen. Before and after the last skin sensitization, the number of scratching incidents and the thickness of the ear were examined, and the plasma levels of OVA-IgE, α-MSH, ACTH, TGF-β and TNF-α were analysed by ELISA. Sensitization of mice with OVA resulted in increased plasma levels of OVA-IgE, α-MSH, ACTH, TGF-β and TNF-α in control, but not in iNOS(-/-) mice. The administration of l-nitro-arginine-methyl ester (l-NAME) abolished all the above changes that occurred in the control mice. In addition, iNOS(-/-) mice given α-MSH exhibited a change similar to that seen in the control, whereas iNOS(-/-) mice given ACTH, TGF-β or TNF-α did not demonstrate any changes. These results indicate that symptoms of AD such as scratching can be exacerbated by α-MSH, which is induced by iNOS-derived NO.

  10. Stressor-responsive central nesfatin-1 activates corticotropin-releasing hormone, noradrenaline and serotonin neurons and evokes hypothalamic-pituitary-adrenal axis

    PubMed Central

    Yoshida, Natsu; Maejima, Yuko; Sedbazar, Udval; Ando, Akihiko; Kurita, Hideharu; Damdindorj, Boldbaatar; Takano, Eisuke; Gantulga, Darambazar; Iwasaki, Yusaku; Kurashina, Tomoyuki; Onaka, Tatsushi; Dezaki, Katsuya; Nakata, Masanori; Mori, Masatomo; Yada, Toshihiko

    2010-01-01

    A recently discovered satiety molecule, nesfatin-1, is localized in neurons of the hypothalamus and brain stem and colocalized with stress-related substances, corticotropin-releasing hormone (CRH), oxytocin, proopiomelanocortin, noradrenaline (NA) and 5-hydroxytryptamine (5-HT). Intracerebroventricular (icv) administration of nesfatin-1 produces fear-related behaviors and potentiates stressor-induced increases in plasma adrenocorticotropic hormone (ACTH) and corticosterone levels in rats. These findings suggest a link between nesfatin-1 and stress. In the present study, we aimed to further clarify the neuronal network by which nesfatin-1 could induce stress responses in rats. Restraint stress induced c-Fos expressions in nesfatin-1-immunoreactive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus, and in the nucleus of solitary tract (NTS), locus coeruleus (LC) and dorsal raphe nucleus (DR) in the brain stem, without altering plasma nesfatin-1 levels. Icv nesfatin-1 induced c-Fos expressions in the PVN, SON, NTS, LC, DR and median raphe nucleus, including PVN-CRH, NTS-NA, LC-NA and DR-5-HT neurons. Nesfatin-1 increased cytosolic Ca2+ concentration in the CRH-immunoreactive neurons isolated from PVN. Icv nesfatin-1 increased plasma ACTH and corticosterone levels. These results indicate that the central nesfatin-1 system is stimulated by stress and activates CRH, NA and 5-HT neurons and hypothalamic-pituitary-adrenal axis, evoking both central and peripheral stress responses. PMID:20966530

  11. Effects of ACTH on corticosteroid and progesterone levels in female baboons depending on the phase of the menstrual cycle

    SciTech Connect

    Todua, T.N.; Goncharov, N.P.; Katsiya, G.V.; Lapin, B.A.; Vorontsov, V.I.

    1986-01-01

    To study the effect of ACTH on the endocrine function of steroid producing glands depending on the level of sex hormones in the body, a comparative study of the dynamics of steroid hormones in the follicular and luteal phases of the menstrual cycle in response to a standard does of ACTH was undertaken in experiments on hamadryad baboons. Concentrations of corticosterone, 11-deoxycortisol, and progesterone were determined in duplicate samples of plasma by radioimmunoassay. It is shown that the sensitivity of the adrenals to a single injection of ACTH is independent of the phase of the menstrual cycle and the inhibitory effects of ACTH on progesterone secretion is exhibited only in the presence of an actively functioning corpus luteus of the ovary.

  12. Ghrelin and GHRP-6-induced ACTH and cortisol release in thyrotoxicosis.

    PubMed

    Nascif, Sergio Oliva; Molica, Patrícia; Correa-Silva, Silvia Regina; Silva, Marcos Roberto; Lengyel, Ana-Maria Judith

    2009-01-01

    Thyrotoxicosis might alter the hypothalamic-pituitary-adrenal (HPA) axis. We evaluated the effects of ghrelin and GHRP-6 on the HPA axis in 20 hyperthyroid patients and in 9 controls. Mean basal cortisol (microg/dl) and ACTH (pg/ml) levels were higher in hyperthyroidism (cortisol: 10.7 +/- 0.7; ACTH: 21.5 +/- 2.9) compared to controls (cortisol: 8.1 +/- 0.7; ACTH: 13.5 +/- 1.8). In thyrotoxicosis Delta AUC cortisol values (microg/dl.90 min) after ghrelin (484 +/- 80) and GHRP-6 (115 +/- 63) were similar to controls (ghrelin: 524 +/- 107; GHRP-6: 192 +/- 73). A significant increase in Delta AUC ACTH (pg/ml x 90 min) after ghrelin was observed in thyrotoxicosis (4,189 +/- 1,202) compared to controls (1,499 +/- 338). Delta AUC ACTH values after GHRP-6 were also higher, although not significantly (patients: 927 +/- 330; controls: 539 +/- 237). In summary, our results suggest that ghrelin-mediated pathways of ACTH release might be activated by thyroid hormone excess, but adrenocortical reserve is maintained.

  13. The ACTH cells in the pituitary gland of the nine-spined stickleback, Pungitius pungitius L.

    PubMed Central

    Benjamin, M

    1982-01-01

    The ACTH cells form a layer 1-8 cells thick, dorsal to the prolactin cells in the rostral pars distalis. They react only mildly with a variety of stains including PAS-lead haematoxylin. Their nuclear diameters vary seasonally in a manner that closely parallels that of the prolactin cells. The relative volumes of the ACTH and prolactin cell zones are remarkably constant in animals of different sizes. It is suggested that the two hormones may act synergistically at various body sites and that this accounts for the related morphological features of the ACTH and prolactin cells. There are no changes in the surface density of the ACTH zone with increasing animal size. Consequently, the ACTH/neurohypophysial border is highly convoluted in large animals. The proximity of the neurohypophysis also influences cell ultrastructure, as small processes, packed with secretory granules are more numerous near the basal lamina separating the adeno- and neurohypophyses. A morphometric analysis of ACTH cells provides base-line ultrastructural data for experimental studies and for comparisons with other teleosts. The cells have small, secretory granules, 100-300 nm in diameter, and of variable electron density. There is little rough endoplasmic reticulum and a small Golgi apparatus. There is no evidence of granule release by exocytosis and various explanations for this are suggested. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:6290440

  14. Cortisol and ACTH levels in drug-naive adolescents with first-episode early onset schizophrenia.

    PubMed

    Şimşek, Şeref; Gençoğlan, Salih; Yüksel, Tuğba; Aktaş, Hüseyin

    2017-03-01

    The aim of this study was to investigate serum levels of cortisol and adrenocorticotropic hormone in adolescents with first-episode early onset schizophrenia. A total of 23 adolescent patients, who did not receive prior therapy and who were diagnosed with psychosis according to DSM-IV, were included. Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version, Positive and Negative Symptom Scale, and Clinical Global Impression Scale were conducted with the participants. No significant differences were found between the patients and the control subjects in serum cortisol and adrenocorticotropic hormone levels (P > .05). Our study's findings do not support the hypothesis of increased hypothalamic-pituitary-adrenal axis activity in first-episode early onset schizophrenia.

  15. ACTH Action on Messenger RNA Stability Mechanisms

    PubMed Central

    Desroches-Castan, Agnès; Feige, Jean-Jacques; Cherradi, Nadia

    2017-01-01

    The regulation of mRNA stability has emerged as a critical control step in dynamic gene expression. This process occurs in response to modifications of the cellular environment, including hormonal variations, and regulates the expression of subsets of proteins whose levels need to be rapidly adjusted. Modulation of messenger RNA stability is usually mediated by stabilizing or destabilizing RNA-binding proteins (RNA-BP) that bind to the 3′-untranslated region regulatory motifs, such as AU-rich elements (AREs). Destabilizing ARE-binding proteins enhance the decay of their target transcripts by recruiting the mRNA decay machineries. Failure of such mechanisms, in particular misexpression of RNA-BP, has been linked to several human diseases. In the adrenal cortex, the expression and activity of mRNA stability regulatory proteins are still understudied. However, ACTH- or cAMP-elicited changes in the expression/phosphorylation status of the major mRNA-destabilizing protein TIS11b/BRF1 or in the subcellular localization of the stabilizing protein Human antigen R have been reported. They suggest that this level of regulation of gene expression is also important in endocrinology. PMID:28163695

  16. Influence of a prenatal stressor on ACTH-induced cortisol secretion in yearling Brahman heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to test whether prenatal stress affects postnatal adrenocortical responsiveness to exogenous adrenocorticotropin-releasing hormone (ACTH) in calves of Brahman cows transported for 2-hour periods at 60, 80, 100, 120, and 140 days of gestation. Prenatally stressed yearl...

  17. Cushing Syndrome Due to ACTH-Secreting Pheochromocytoma, Aggravated by Glucocorticoid-Driven Positive-Feedback Loop

    PubMed Central

    Sakuma, Ikki; Higuchi, Seiichiro; Fujimoto, Masanori; Takiguchi, Tomoko; Nakayama, Akitoshi; Tamura, Ai; Kohno, Takashi; Komai, Eri; Shiga, Akina; Nagano, Hidekazu; Hashimoto, Naoko; Suzuki, Sawako; Mayama, Takafumi; Koide, Hisashi; Ono, Katsuhiko; Sasano, Hironobu; Tatsuno, Ichiro; Yokote, Koutaro

    2016-01-01

    Context: Pheochromocytoma is a catecholamine-producing tumor that originates from adrenal chromaffin cells and is capable of secreting various hormones, including ACTH. Case Description: A 56-year-old female presented with Cushingoid appearance and diabetic ketoacidosis. Endocrinological examinations demonstrated ectopic ACTH production with hypercortisolemia and excess urinary cortisol accompanied by elevated plasma and urine catecholamines. Computed tomography revealed a large left adrenal tumor with bilateral adrenal enlargement. Metaiodobenzylguanidine scintigraphy revealed abnormal accumulation in the tumor, which was eventually diagnosed as pheochromocytoma with ectopic ACTH secretion with subsequent manifestation of Cushing's syndrome. Ectopic ACTH secretion and catecholamine production were blocked by metyrapone treatment, whereas dexamethasone paradoxically increased ACTH secretion. Left adrenalectomy resulted in complete remission of Cushing's syndrome and pheochromocytoma. In Vitro Studies: Immunohistological analysis revealed that the tumor contained two functionally distinct chromaffin-like cell types. The majority of tumor cells stained positive for tyrosine hydroxylase (TH), whereas a minor population of ACTH-positive tumor cells was negative for TH. Furthermore, gene expression and in vitro functional analyses using primary tumor tissue cultures demonstrated that dexamethasone facilitated ACTH as well as catecholamine secretion with parallel induction of proopiomelanocortin (POMC), TH, and phenylethanolamine N-methyltransferase mRNA, supporting a glucocorticoid-dependent positive-feedback loop of ACTH secretion in vivo. DNA methylation analysis revealed that the POMC promoter of this tumor, particularly the E2F binding site, was hypomethylated. Conclusion: We present a case of ectopic ACTH syndrome associated with pheochromocytoma. ACTH up-regulation with paradoxical response to glucocorticoid, possibly through the hypomethylation of the POMC

  18. Hormones

    MedlinePlus

    ... affect many different processes, including Growth and development Metabolism - how your body gets energy from the foods you eat Sexual function Reproduction Mood Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the ...

  19. Plasma N-POMC, ACTH and cortisol concentrations in a psychogeriatric population.

    PubMed

    Leake, A; Charlton, B G; Lowry, P J; Jackson, S; Fairbairn, A; Ferrier, I N

    1990-05-01

    Elderly patients with depression and Alzheimer-type dementia (ATD) were compared with age-matched control subjects using a protocol which measured cortisol, adrenocorticotrophic hormone (ACTH) and N-terminal pro-opiomelanocortin (N-POMC) to determine diurnal variation and the effect of dexamethasone administration. Depressed patients had significantly elevated cortisol concentrations both before and after dexamethasone administration. Basal ACTH and N-POMC concentrations were normal in depressed patients but were both elevated, compared with controls, after dexamethasone. By contrast, in ATD patients, cortisol was elevated only after dexamethasone, as was ACTH, but not N-POMC. This may imply that the pattern of secretion of POMC-derived peptides underlying increased cortisol secretion is different in ATD from that in depression.

  20. Proopiomelanocortin, glucocorticoid, and CRH receptor expression in human ACTH-secreting pituitary adenomas.

    PubMed

    Cassarino, Maria Francesca; Sesta, Antonella; Pagliardini, Luca; Losa, Marco; Lasio, Giovanni; Cavagnini, Francesco; Pecori Giraldi, Francesca

    2017-03-01

    ACTH-secreting pituitary tumors are by definition partially autonomous, i.e., secrete ACTH independent of physiological control. However, only few, small-sized studies on proopiomelanocortin (POMC) and its regulation by corticotropin-releasing hormone (CRH) or glucocorticoids are available. Objective of the present study was to report on constitutive and CRH- and dexamethasone-regulated POMC, CRH (CRH-R1), and glucocorticoid receptor (NR3C1) gene expression in a large series of human corticotrope adenomas. Fifty-three ACTH-secreting adenomas were incubated with 10 nM CRH or 10 nM dexamethasone for 24 h. POMC, CRH-R1, NR3C1, and its alpha and beta isoforms were quantified and medium ACTH measured. Constitutive POMC expression proved extremely variable, with macroadenomas exhibiting higher levels than microadenomas. POMC increased during CRH in most specimens; conversely, changes induced by dexamethasone were varied, ranging from decrease to paradoxical increase. No correlation between POMC and ACTH was detected in any experimental condition. CRH-R1 expression was not linked to the response to CRH while NR3C1 was expressed at greater levels in specimens who failed to inhibit during dexamethasone; glucocorticoid receptor α was the more abundant isoform and subject to down-regulation by dexamethasone. Our results demonstrate a considerable variability in POMC expression among tumors and no correlation between POMC and ACTH, suggesting that POMC peptide processing/transport plays a major role in modulating ACTH secretion. Further, CRH-R1 and NR3C1 expression were not linked to the expected ligand-induced outcome, indicating that receptor signaling rather than abundance determines corticotrope responses. Our findings pave the way to new avenues of research into Cushing's disease pathophysiology.

  1. Association of PCB, PBDE and PCDD/F body burdens with hormone levels for children in an e-waste dismantling area of Zhejiang Province, China.

    PubMed

    Xu, Peiwei; Lou, Xiaoming; Ding, Gangqiang; Shen, Haitao; Wu, Lizhi; Chen, Zhijian; Han, Jianlong; Han, Guangen; Wang, Xiaofeng

    2014-11-15

    Increased electronic waste (e-waste) has raised public concerns regarding exposure to numerous toxic contaminants, particularly polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). In China, the body burdens of PCBs, PBDEs and PCDD/Fs are associated with thyroid hormones in populations from e-waste dismantling sites; however, it is unclear whether this association occurs in children. In this study, we determined the serum levels of PCBs, PBDEs and PCDD/Fs and the endocrine hormones including free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), total thyroxine (TT4), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), cortisol and growth hormone (GH) in 21 children from an e-waste dismantling area and 24 children from a control area. The results showed that the mean levels of ∑PCBs and ∑PBDEs in the exposure group were significantly higher than in the control group (40.56 and 32.09 ng g(-1) lipid vs. 20.69 and 8.43 ng g(-1) lipid, respectively, p<0.01 for each), and the mean level of ∑PCDD/Fs in the exposure group was higher than in the control group, but the difference was not significant (206.17 vs. 160.27 pg g(-1) lipid, p>0.05). For the endocrine hormones, we did not find significant differences between the exposed and control groups, although the mean levels of FT3, TT3, TT4, ACTH, cortisol and GH were higher, whereas the mean levels of FT4 and TSH were lower in the exposed group. The mean level of ∑PBDEs was positively correlated with the mean levels of ∑PCBs (r=0.60, p<0.05) and ∑PCDD/Fs (r=0.61, p<0.05). Furthermore, the mean level of ∑PBDEs was positively correlated with ACTH (r=0.61, p<0.05). In conclusion, our data suggested that exposure to e-waste dismantling environment increased the body burdens of PCBs and PBDEs in local children and that these contaminants released from the e-waste might contribute to

  2. Ionic dependence of adrenal steroidogenesis and ACTH-induced changes in the membrane potential of adrenocortical cells

    PubMed Central

    Matthews, E. K.; Saffran, M.

    1973-01-01

    1. The effects of changes of ionic environment upon corticosteroid production by rabbit adrenal glands have been investigated in vitro using a superfusion technique and on-line steroid analysis by an automated fluorescence method. In some experiments micro-electrode recordings of adrenocortical transmembrane potentials were made concomitantly with measurement of steroid output. 2. Adrenocorticotrophic hormone (ACTH), 10 m-u./ml., induced a sevenfold increase in corticosteroid production rate in normal Krebs solution. 3. The steroidogenic response to ACTH was not impaired after omission of [K]o for 1 hr but was inhibited following exposure to K+-free medium for 3 hr. Increase of [K]o tenfold to 47 mM increased the basal but not the ACTH-stimulated output of corticosteroid whereas raising [K]o twentyfold to 94 mM enhanced both the basal and ACTH-stimulated steroid production rate. In K+-free solution the adrenocortical cells hyperpolarized from - 67 to - 86 mV; subsequently on addition of ACTH they depolarized. Reintroduction of K+ restored the membrane potential. 4. Omission of Ca2+ partially depolarized the cells but only affected the steroidogenic response to ACTH in the presence of EDTA. A threefold increase of [Ca]o, to 7·68 mM, had no effect on either membrane potentials or steroid formation, but increasing [Ca]o tenfold to 25·6 mM partially blocked ACTH action. Increasing [Mg]o twentyfold to 22·6 mM had little effect on ACTH-stimulated corticosteroid output and Sr 2·56 mM, in substitution for Ca2+, supported ACTH action, but La, 0·25 mM, completely blocked the steroidogenic effect of ACTH. 5. Replacement of NaCl, 118 mM by choline chloride, 118 mM, was without effect on ACTH-induced steroidogenesis, whereas LiCl, 118 mM, reduced it by 50%. NaF, 1 and 10 mM, inhibited ACTH-induced steroidogenesis by approximately 60%. 6. Nupercaine, 10-4 M, inhibited the steroid response to ACTH with no effect upon membrane potentials: increasing the nupercaine

  3. Replacement therapy: arginine vasopressin (AVP), growth hormone (GH), cortisol, thyroxine, testosterone and estrogen.

    PubMed

    Mitchell, D H; Owens, B

    1996-06-01

    Replacement therapy is routinely used to treat hormone deficiencies of patients who have had surgery or radiation therapy that damages the hypothalamus or pituitary gland. Hormones commonly replaced include: arginine vasopressin (AVP), growth hormone (GH), cortisol, thyroxine (T4), testosterone and estrogen. AVP, synthesized in the hypothalamus, is stored in and released by the posterior lobe of the pituitary gland. GH is synthesized and released by the anterior pituitary gland. The other hormones are produced and released by target glands each of which is stimulated by a specific anterior pituitary hormone, which in turn is controlled by release of a specific hypothalamic hormone. Feedback control by a high circulating concentration of the target gland's hormone regulates hypothalamic hormone release. Deficiency of AVP, important for water balance in the body, is restored with the synthetic analogue, 1-desamino-8-D-arginine vasopressin (DDAVP); it is given as a nasal spray or by injection. GH is required for normal growth in the developing child; recombinant GH, produced in bacteria, is injected subcutaneously. Adrenocorticotropic hormone (ACTH) controls release of cortisol which is produced by the adrenal cortex and enables the body to cope with stress; cortisol is replaced with prednisolone given orally. Thyroid stimulating hormone (TSH) controls release of the thyroid hormones, T4 and triiodothyronine (T3), which promote growth and development, and regulate energy metabolism; for replacement of T4, oral synthetic L-thyroxine is given. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) control release of testosterone, which promotes maturation of sperm and development of male sexual characteristics; replacement testosterone is administered intramuscularly. In females, FSH and LH control release of estrogens and progesterone which prepare the reproductive tract for release of the ovum, fertilization, implantation and development of the embryo

  4. The effect of ACTH on suckling rats.

    PubMed

    Sato, Y

    1984-01-01

    In the present study, the causes of brain shrinkage induced by synthetic ACTH treatment in epileptic children were investigated using suckling rats. Synthetic ACTH was injected subcutaneously once a day for 5 days into suckling rats aged 15 days. Saline was injected into control subjects in the same way. Rats were sacrificed before the injection, immediately after the repeated injections, and 5 and 14 days from the end of the course of repeated injections. The weight, volume and water content of the brains were measured and the protein, DNA, sodium and potassium contents of the brains were also determined. The mean weight and volume of the brains after 5-day injection of ACTH were slightly smaller compared to those of control rats. No natural increase in brain protein with growth was found from the start of ACTH injections to 14 days after finishing the course of repeated injections. The DNA, sodium and potassium contents of the brains significantly increased immediately after the repeated injections of 5 days. It was suggested that the brain shrinkage of epileptics induced by ACTH treatment might be caused by decreased water content and not cellular degradation.

  5. Leptin Alters Adrenal Responsiveness by Decreasing Expression of ACTH-R, StAR, and P450c21 in Hypoxemic Fetal Sheep

    PubMed Central

    Su, Yixin; Carey, Luke C.; Pulgar, Victor M.

    2012-01-01

    The late gestation increase in adrenal responsiveness to adrenocorticotropin (ACTH) is dependent upon the upregulation of the ACTH receptor (ACTH-R), steroidogenic acute regulatory protein (StAR), and steroidogenic enzymes in the fetal adrenal. Long-term hypoxia decreases the expression of these and adrenal responsiveness to ACTH in vivo. Leptin, an adipocyte-derived hormone which attenuates the peripartum increase in fetal plasma cortisol is elevated in hypoxic fetuses. Therefore, we hypothesized that increases in plasma leptin will inhibit the expression of the ACTH-R, StAR, and steroidogenic enzymes and attenuate adrenal responsiveness in hypoxic fetuses. Spontaneously hypoxemic fetal sheep (132 days of gestation, PO2 ∼15 mm Hg) were infused with recombinant human leptin (n = 8) or saline (n = 7) for 96 hours. An ACTH challenge was performed at 72 hours of infusion to assess adrenal responsiveness. Plasma cortisol and ACTH were measured daily and adrenals were collected after 96 hours infusion for messenger RNA (mRNA) and protein expression measurement. Plasma cortisol concentrations were lower in leptin- compared with saline-infused fetuses (14.8 ± 3.2 vs 42.3 ± 9.6 ng/mL, P < .05), as was the cortisol:ACTH ratio (0.9 ± 0.074 vs 46 ± 1.49, P < .05). Increases in cortisol concentrations were blunted in the leptin-treated group after ACTH1-24 challenge (F = 12.2, P < .0001). Adrenal ACTH-R, StAR, and P450c21 expression levels were reduced in leptin-treated fetuses (P < .05), whereas the expression of Ob-Ra and Ob-Rb leptin receptor isoforms remained unchanged. Our results indicate that leptin blunts adrenal responsiveness in the late gestation hypoxemic fetus, and this effect appears mediated by decreased adrenal ACTH-R, StAR, and P450c21 expression. PMID:22534336

  6. ACTH and prednisone in childhood seizure disorders.

    PubMed

    Snead, O C; Benton, J W; Myers, G J

    1983-08-01

    We treated 116 children with ACTH or prednisone. Fifty-two had infantile spasms with hypsarhythmia, and 64 had other types of intractable seizures. ACTH completely controlled seizures in all patients with infantile spasms and hypsarhythmia and 74% of those with other types of seizures. Prednisone controlled 51% of patients with infantile spasms and none with other seizures. Serious side effects were minimal for both drugs, and recurrent seizures occurred in 40 to 50% of patients within 4 to 14 months after completion of therapy.

  7. Effects of ACTH on the last step of aldosterone biosynthesis.

    PubMed

    Cozza, E N; Ceballos, N R; Lantos, C P

    1989-12-01

    The production of tritiated aldosterone and tritiated SM (a saponifiable 18-hydroxycorticosterone derivative) by rat adrenals were studied at various incubation times in absence or presence of two concentrations of ACTH. Tritiated 18-hydroxycorticosterone or 18-deoxyaldosterone served as precursors. The lower ACTH concentration (150 pM) increased the production of tritiated aldosterone. Whereas, the higher ACTH concentration (1.5 microM) stimulated tritiated aldosterone production at shorter incubation time (30 min), while after 60 min it inhibited. This time dependency would reflect variations in the levels of endogenous steroids. On the other hand, the effects of ACTH on tritiated SM production were opposite to those on tritiated aldosterone. In effect, while 150 pM ACTH inhibited SM production, 1.5 microM ACTH stimulated it. These results suggest that ACTH promotes opposite effects on the productions of aldosterone and SM and therefore both productions would be coordinated under the regulation of ACTH.

  8. Treatment of infantile spasms with high-dose ACTH: efficacy and plasma levels of ACTH and cortisol.

    PubMed

    Snead, O C; Benton, J W; Hosey, L C; Swann, J W; Spink, D; Martin, D; Rej, R

    1989-08-01

    Fifteen children with infantile spasms and a hypsarrhythmic EEG defined by EEG-videotelemetry monitoring received a regimen of high-dose (150 IU/m2/d) ACTH for their seizures. We carried out an endocrinologic evaluation before and after initiation of the ACTH and conducted a time course study of plasma ACTH and cortisol levels after ACTH dosing. Spasms were controlled and the EEG normalized in 14 of the 15 children. Prior to starting ACTH therapy all the patients had normal prolactin, insulin, cortisol, and ACTH levels in plasma and normal thyroid function. Although the pattern of rise of ACTH levels in plasma after ACTH dosing was similar in all the children, there was great individual variation in the absolute concentrations. However, both the pattern of rise and absolute level of cortisol in plasma after ACTH was highly predictable in all patients. Plasma cortisol rose rapidly within 1 hour of ACTH administration and continued a slower rise for 12 to 24 hours after the ACTH dose. High-dose ACTH therapy seems quite effective in infantile spasms, perhaps because of a sustained high level of plasma cortisol. This sustained plateau of cortisol may be more effective in controlling infantile spasms than the pulse effect expected with oral steroids or lower doses of ACTH.

  9. Hormone therapy in acne.

    PubMed

    Lakshmi, Chembolli

    2013-01-01

    Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne.

  10. Release of Multiple Hormones by a Direct Action of Interleukin-1 on Pituitary Cells

    DTIC Science & Technology

    1987-10-23

    monolayer culture was investigated. Recombinant human IL-I beta stimulated the secretion of adrenocorticotropic hormone, luteinizing hormone, growth ... hormone , and thyroid-stimulating hormone. Prolactin secretion by the monolayers was inhibited by similar doses. These concentrations of IL-I are within

  11. Brain sites mediating corticosteroid feedback inhibition of stimulated ACTH secretion

    SciTech Connect

    Jacobson, L.

    1989-01-01

    There is substantial evidence that the brain mediates stress-induced and circadian increases in ACTH secretion and that corticosteroid concentrations which normalize basal plasma ACTH are insufficient to normalize ACTH responses to circadian or stressful stimuli in adrenalectomized rats. To identify brain sites mediating corticosteroid inhibition of stimulated ACTH secretion, two approaches were used. The first compared brain ({sup 14}C)-2-deoxyglucose uptake in rats with differential ACTH responses to stress. Relative to sham-adrenalectomized (SHAM) rats, adrenalectomized rats replaced with low, constant corticosterone levels via a subcutaneous corticosterone pellet (B-PELLET) exhibited elevated and prolonged ACTH responses to a variety of stimuli. Adrenalectomized rate given a circadian corticosterone rhythm via corticosterone in their drinking water exhibited elevated ACTH levels immediately after stress, but unlike B-PELLET rats, terminated stress induced ACTH secretion normally relative to SHAMS. Therefore, the abnormal ACTH responses to stress in B-PELLET rats were due to the lack of both circadian variations and stress-induced increases in corticosterone. Hypoxia was selected as a standardized stimulus for correlating brain ({sup 14}C)-2-deoxyglucose uptake with ACTH secretion. In intact rats, increases in plasma ACTH and decreases in arterial PO{sub 2} correlated with the severity of hypoxia at arterial PCO{sub 2} below 60 mm Hg. Hypoxia PELLET vs. SHAM rats. However, in preliminary experiments, although hypoxia increased brain 2-deoxyglucose uptake in most brain regions, plasma ACTH correlated poorly with 2-deoxyglucose uptake at 12% and 10% O{sub 2}.

  12. Environmental prenatal stress eliminates brain and maternal behavioral sex differences and alters hormone levels in female rats.

    PubMed

    Del Cerro, M C R; Ortega, E; Gómez, F; Segovia, S; Pérez-Laso, C

    2015-07-01

    Environmental prenatal stress (EPS) has effects on fetuses that are long-lasting, altering their hormone levels, brain morphology and behavior when they reach maturity. In previous research, we demonstrated that EPS affects the expression of induced maternal behavior (MB), the neuroendocrine system, and morphology of the sexually dimorphic accessory olfactory bulb (AOB) involved in reproductive behavior patterns. The bed nucleus of the accessory olfactory tract (BAOT) is another vomeronasal (VN) structure that plays an inhibitory role in rats in the expression of induced maternal behavior in female and male virgins. In the present study, we have ascertained whether the behavioral, neuroendocrine, and neuromorphological alterations of the AOB found after EPS also appear in the BAOT. After applying EPS to pregnant rats during the late gestational period, in their female offspring at maturity we tested induced maternal behavior, BAOT morphology and plasma levels of testosterone (T), estradiol (E2), progesterone (P), adrenocorticotropic hormone (ACTH) and corticosterone (Cpd B). EPS: a) affected the induction of MB, showed a male-like pattern of care for pups, b) elevated plasma levels of Cpd B and reduced E2 in comparison with the controls, and c) significantly increased the number of BAOT neurons compared to the control females and comparable to the control male group. These findings provide further evidence that stress applied to pregnant rats produces long-lasting behavioral, endocrine and neuroanatomical alterations in the female offspring that are evident when they become mature.

  13. Mitotane reduces human and mouse ACTH-secreting pituitary cell viability and function.

    PubMed

    Gentilin, Erica; Tagliati, Federico; Terzolo, Massimo; Zoli, Matteo; Lapparelli, Marcello; Minoia, Mariella; Ambrosio, Maria Rosaria; Degli Uberti, Ettore C; Zatelli, Maria Chiara

    2013-09-01

    Medical therapy for Cushing's disease (CD) is currently based on agents mainly targeting adrenocortical function. Lately, pituitary-directed drugs have been developed, with limited efficacy. Mitotane, a potent adrenolytic drug, has been recently investigated for the treatment of CD, but the direct pituitary effects have not been clarified so far. The aim of our study was to investigate whether mitotane may affect corticotroph function and cell survival in the mouse pituitary cell line AtT20/D16v-F2 and in the primary cultures of human ACTH-secreting pituitary adenomas, as an in vitro model of pituitary corticotrophs. We found that in the AtT20/D16v-F2 cell line and in primary cultures, mitotane reduces cell viability by inducing caspase-mediated apoptosis and reduces ACTH secretion. In the AtT20/D16v-F2 cell line, mitotane reduces Pomc expression and blocks the stimulatory effects of corticotropin-releasing hormone on cell viability, ACTH secretion, and Pomc expression. These effects were apparent at mitotane doses greater than those usually necessary for reducing cortisol secretion in Cushing's syndrome, but still in the therapeutic window for adrenocortical carcinoma treatment. In conclusion, our results demonstrate that mitotane affects cell viability and function of human and mouse ACTH-secreting pituitary adenoma cells. These data indicate that mitotane could have direct pituitary effects on corticotroph cells.

  14. Analysis of the brain ACTH-immunoreactive peptide spectrum in inbred mice

    SciTech Connect

    Fedoseev, Yu.L.; Blednov, Yu.A.; Seredenin, S.B.

    1987-01-01

    Mice of the BALB/c (C) and C57BL/6 (B6) strains, characterized by high and low emotionality respectively in open field tests, have been shown to differ considerably in both the initial level and the time course of changes in the plasma ACTH concentration after exposure to stress in an open field and after administration of a benzodiazepine tranquilizer. The ACTH concentration in the pituitary gland of animals of these lines also differs. The ACTH molecule is known to contain regions with neurotropic activity. It can therefore be postulated that differences in the level of this hormone and the products of its bioconversion in the brain are an essential factor in the mechanisms of formation of the hereditary features of emotional behavior. In this first stage of this investigation, represented in this paper and undertaken to test this hypothesis, spectra of ACTH-immunoreactive peptides were studied in chromatographic fractions of an acid brain extract as well as in the blood plasma of mice belonging to B6 and C lines and their hybrids. The peptides were determined by radioimmunoassay.

  15. ACTH, corticosterone, and beta-endorphin in rat blood plasma after prolonged immobilization stress

    SciTech Connect

    Kiyatkin, E.A.; Amiragova, M.G.; Kushlinskii, N.E.; Polyntsev, Yu. V.

    1986-01-01

    To assess functional relations between changes in ACTH, beta-endorphin (BE), and corticosterone (CS) levels, plasma concentrations of these hormones were studied in rats during the development of prolonged immobilization stress. Plasma hormone concentrations were determined by radioimmunoassay. The results were analyzed by standard statistical methods on a microcomputer. A particular feature about the kit used to determine BE was the presence of 50% cross-reactivity of the antiserum against beta-lipotrophin. To determine CS a highly specific antiserum produced by a laboratory was used.

  16. Effects of smoking on ACTH and cortisol secretion

    SciTech Connect

    Seyler, L.E. Jr.; Fertig, J.; Pomerleau, O.; Hunt, D.; Parker, K.

    1984-01-02

    The relationships among changes in plasma nicotine, ACTH, and cortisol secretion after smoking were investigated. Ten male subjects smoked cigarettes containing 2.87 mg nicotine and 0.48 mg nicotine. No rises in cortisol or ACTH were detected after smoking 0.48 mg nicotine cigarettes. Cortisol rises were significant in 11 of 15 instances after smoking 2.87 mg nicotine cigarattes, but ACTH rose significantly in only 5 of the 11 instances where cortisol increased. Each ACTH rise occurred in a subject who reported nausea and was observed to be pale, sweaty, and tachycardic. Peak plasma nicotine concentrations were not significantly different in sessions when cortisol rose with or without ACTH increases, but cortisol increases were significantly greater in nauseated than in non-nauseated smokers. This data suggest that smoking-induced nausea stimulates cortisol release by stimulating ACTH secretion and that cortisol secretion in non-nauseated smokers may occur through a non-ACTH mechanism.

  17. A case of isolated ACTH deficiency who developed autoimmune-mediated hypothyroidism and impaired water diuresis during glucocorticoid replacement therapy.

    PubMed

    Kageyama, Y

    2000-12-01

    A case of isolated ACTH deficiency who developed autoimmune-mediated hypothyroidism and still showed impaired water diuresis during glucocorticoid replacement therapy is reported. A 45-year-old woman was initially admitted for nausea, vomiting, and general malaise. Her serum sodium and plasma osmolality, ACTH and cortisol values were low, but her urine osmolality was high. Other pituitary hormone levels, thyroid hormone levels, and a computed tomogram of the pituitary gland were normal. The patient was treated with hydrocortisone and followed in the outpatient clinic; however, she was lost to follow up 18 months after admission. Three years later she presented with hypoglycemia and hyponatremia. Her serum or plasma ACTH, FT3, FT4, cortisol levels were low and her serum TSH level was high. Pituitary stimulation tests revealed a blunted response of ACTH to CRH and an exaggerated response of TSH to TRH. Plasma ADH was inappropriately high, and a water-loading test revealed impaired water diuresis and poor suppression of ADH. Although ADH was suppressed, impaired water diuresis was observed in the water loading test after hydrocortisone supplementation. Thyroxine supplementation completely normalized the water diuresis. Her outpatient clinic medical records revealed a gradual increase in TSH levels during follow up, indicating that she had developed hypothyroidism during glucocorticoid replacement therapy. The hyponatremia on the first admission was due to glucocorticoid deficiency, whereas the hyponatremia on the second admission was due to combined deficiencies of glucocorticoid and thyroid hormones.

  18. Mapping of the gene encoding the melanocortin-1 ([alpha]-melanocyte stimulating hormone) receptor (MC1R) to human chromosome 16q24. 3 by fluorescence in situ hybridization

    SciTech Connect

    Gantz, I.; Yamada, Tadataka; Tashiro, Takao; Konda, Yoshitaka; Shimoto, Yoshimasa; Miwa, Hiroto; Trent, J.M. )

    1994-01-15

    [alpha]-Melanocyte stimulating hormone ([alpha]-MSH), a hormone originally named for its ability to regulate pigmentation of melanocytes, is a 13-amino-acid post-translational product of the pro-opiomelanocortin (POMC) gene. [alpha]-MSH and the other products of POMC processing, which share the core heptapeptide amino acid sequence Met-Glu (Gly)-His-Phe-Arg-Trp-Gly (Asp), the adrenocorticotropic hormone (ACTH), [beta]-MSH, and [gamma]-MSH, are collectively referred to as melanocortins. While best known for their effects on the melanocyte (pigmentation) and adrenal cortical cells (steroidogenesis), melanocortins have been postulated to function in diverse activities, including enhancement of learning and memory, control of the cardiovascular system, analgesia, thermoregulation, immunomodulation, parturition, and neurotrophism. To identify the chromosomal band encoding the human melanocortin-1 receptor gene, 1 [mu]g of an EMBL clone coding region of the human MC1R and approximately 15 kb of surrounding DNA was labeled with biotin and hybridized to human metaphase chromosomes as previously described. The results indicate that the human MC1R gene is localized to 16q24.3. 15 refs., 1 fig.

  19. Possible ACTH-independent, cortisol-secreting and DHEA-secreting metastatic hepatocellular carcinoma causing Cushing's syndrome.

    PubMed

    Sacerdote, Alan; Inoue, Taiga; Thomas, Nithin; Bahtiyar, Gul

    2015-12-23

    Cortisol production by hepatocellular carcinoma (HCC) has not been previously reported and dehydroepiandrosterone (DHEA) secretion by HCC is rare. We report a case of a 53-year-old woman admitted with dyspnoea and headache. Serum cortisol by immunoassay (IA) was 42.3 μg/dL, urine free cortisol (UFC) by liquid chromatography mass spectrometry (LC/MS/MS) was 106.1 μg/24 h, serum DHEA by LC/MS/MS was 4886 ng/mL, serum DHEA-S by LC/MS/MS was 4477 ng/mL and plasma adrenocorticotrophic hormone (ACTH) by IA was 10 pg/mL. CT showed likely HCC metastatic to the left adrenal gland, brain and lungs. Liver and adrenal gland biopsies confirmed HCC. ACTH tumour staining was negative. High serum and UFC levels and high serum DHEA and DHEA-S with low-normal plasma ACTH and negative tumour ACTH staining suggested ACTH-independent ectopic Cushing's syndrome (CS); cortisol and DHEA being likely secreted by the HCC. To the best of our knowledge, this is the first reported case of HCC associated with CS.

  20. Differential Activation in Amygdala and Plasma Noradrenaline during Colorectal Distention by Administration of Corticotropin-Releasing Hormone between Healthy Individuals and Patients with Irritable Bowel Syndrome.

    PubMed

    Tanaka, Yukari; Kanazawa, Motoyori; Kano, Michiko; Morishita, Joe; Hamaguchi, Toyohiro; Van Oudenhove, Lukas; Ly, Huynh Giao; Dupont, Patrick; Tack, Jan; Yamaguchi, Takuhiro; Yanai, Kazuhiko; Tashiro, Manabu; Fukudo, Shin

    2016-01-01

    Irritable bowel syndrome (IBS) often comorbids mood and anxiety disorders. Corticotropin-releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis, but it is not clear how CRH agonists change human brain responses to interoceptive stimuli. We tested the hypothesis that brain activation in response to colorectal distention is enhanced after CRH injection in IBS patients compared to healthy controls. Brain H215O- positron emission tomography (PET) was performed in 16 male IBS patients and 16 age-matched male controls during baseline, no distention, mild and intense distention of the colorectum using barostat bag inflation. Either CRH (2 μg/kg) or saline (1:1) was then injected intravenously and the same distention protocol was repeated. Plasma adrenocorticotropic hormone (ACTH), serum cortisol and plasma noradrenaline levels were measured at each stimulation. At baseline, CRH without colorectal distention induced more activation in the right amygdala in IBS patients than in controls. During intense distention after CRH injection, controls showed significantly greater activation than IBS patients in the right amygdala. Plasma ACTH and serum cortisol secretion showed a significant interaction between drug (CRH, saline) and distention. Plasma noradrenaline at baseline significantly increased after CRH injection compared to before injection in IBS. Further, plasma noradrenaline showed a significant group (IBS, controls) by drug by distention interaction. Exogenous CRH differentially sensitizes brain regions of the emotional-arousal circuitry within the visceral pain matrix to colorectal distention and synergetic activation of noradrenergic function in IBS patients and healthy individuals.

  1. Voluntary wheel running modulates glutamate receptor subunit gene expression and stress hormone release in Lewis rats.

    PubMed

    Makatsori, A; Duncko, R; Schwendt, M; Moncek, F; Johansson, B B; Jezova, D

    2003-07-01

    Lewis rats that are known to be addiction-prone, develop compulsive running if they have access to running wheels. The present experiments were aimed 1) to evaluate the activation of stress systems following chronic and acute voluntary wheel running in Lewis rats by measurement of hormone release and gene expression of neuropeptides related to hypothalamic-pituitary-adrenocortical (HPA) axis activity and 2) to test the hypothesis that wheel running as a combined model of addictive behavior and stress exposure is associated with modulation of ionotropic glutamate receptor subunits in the ventral tegmental area. Voluntary running for three weeks but not for one night resulted in a rise in plasma corticosterone and adrenocorticotropic hormone (ACTH) levels (p<0.05) compared to those in control rats. Principal component analysis revealed the relation between POMC gene expression in the intermediate pituitary and running rate. Acute exposure of animals to voluntary wheel running induced a significant decrease in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor GluR1 subunit mRNA levels (p<0.01), while repeated voluntary physical activity increased levels of GluR1 mRNA in the ventral tegmentum (p<0.05). Neither acute nor chronic wheel running influenced N-methyl-D-aspartate (NMDA) receptor subunit NR1 mRNA levels in the ventral tegmental area. Thus, the present study revealed changes in AMPA receptor subunit gene expression in a reward-related brain structure as well as an activation of HPA axis in response to compulsive wheel running in Lewis rats. It may be suggested that hormones of HPA axis and glutamate receptors belong to the factors that substantiate higher vulnerability to addictive behavior.

  2. Regulation of the Immune System by Hypothalamic Releasing Hormones.

    DTIC Science & Technology

    1987-11-01

    Meyer, W.J. 1987. Decreased mononuclear leukocyte TSH secretion in patients with major depression. Abstr. Society for Neuroscience. 14. Smith, E.M...corticotropin (ACTH). Also, presented are results that the hypothalamic releasing hormones for luteinizing hormone (LH) and thyrotropin ( TSH ) induce...lymphocytes to synthesize immunoreactive LH and TSH , respectively. Finally, we discuss our data that the ACTH receptor on lymphoeytes acts through

  3. Short-term effects of cortisol implantation on blood biochemistry and thyroid hormones in previtellogenic great sturgeon Huso huso.

    PubMed

    Poursaeid, Samaneh; Falahatkar, Bahram; Van Der Kraak, Glen

    2015-01-01

    This study examined the effects of implanted cortisol on various aspects of intermediary metabolism of great sturgeon, Huso huso. Prior to experimentation all fish were examined using an endoscope to observe the stage of ovarian development. Subsequently, the 3-year-old female fish in the previtellogenic stage (mean body weight of 6759±53.2g) were intraperitoneally implanted with cocoa butter pellets containing cortisol to mimic the effects of chronic stress. The implant doses were 0 (C0; as control), 5 (C5) and 50 (C50) mg cortisol/kg body weight. Blood samples were taken every seven days during the four weeks of the experiment and analyzed for cortisol, glucose, adrenocorticotropic hormone (ACTH), total protein, total lipid, triiodothyronine (T3), thyroxine (T4), cholesterol and triglyceride content. Growth was reduced in all experimental groups and was not affected by cortisol treatment. Surprisingly, serum cortisol levels were higher in the C5 group than in the C50 throughout the experiment. A significant increase in glucose levels was observed in the cortisol-implanted fish from day 14 onwards. The high dose of cortisol elicited a significant increase in serum T3 and T4 levels. Fish implanted with the high cortisol dose also showed increases in serum ACTH, total lipid and cholesterol levels throughout a 28-day experimental period. The present study reveals that the negative effects of endoscopic surgery remain for at least four weeks and that a sustained-release implant of cortisol to mimic the effects of chronic stress affects metabolic responses. Since the adverse effects of endoscopic surgery on sturgeon welfare can be amplified by cortisol, special attention should be paid to the potential effects of chronic stress on sturgeon in culture.

  4. Acute melatonin and para-chloroamphetamine interactions on pineal, brain and serum serotonin levels as well as stress hormone levels.

    PubMed

    Manzana, E J; Chen, W J; Champney, T H

    2001-08-03

    para-Chloroamphetamine, an amphetamine analog, alters serotonergic neurochemistry. In previous reports, melatonin (MEL), when administered with other amphetamine analogs, altered the decline in serotonin content produced by these analogs. The present studies assessed the effects of various doses of melatonin and p-chloroamphetamine on serotonin levels in numerous brain regions in male rats. Melatonin (10, 25 or 50 mg/kg, s.c.) and p-chloroamphetamine (3 or 5 mg/kg, s.c.) were administered and, 3 h later, brain samples and serum were collected. Serotonin levels in the serum and various regions of the brain were assayed using high-performance liquid chromatography. Melatonin in combination with a high dose of p-chloroamphetamine (5 mg/kg) produced cumulative deficits in serotonin levels in the serum. However, serotonin levels in the pineal, cortex or brain stem in all combined melatonin and p-chloroamphetamine groups were not significantly different from groups that received p-chloroamphetamine alone. Serum adrenocorticotropin (ACTH) and corticosterone levels were significantly elevated in the melatonin and p-chloroamphetamine combined groups, suggesting that animals receiving both treatments were more stressed than control animals or animals receiving melatonin or p-chloroamphetamine alone. These results indicate that melatonin does not alter p-chloroamphetamine-induced deficits in central serotonin levels. The increased serum adrenocorticotropic hormone, corticosterone and serotonin levels observed following melatonin and p-chloroamphetamine treatment suggest that this combination may have adverse peripheral effects.

  5. CRH stimulation of corticosteroids production in melanocytes is mediated by ACTH.

    PubMed

    Slominski, Andrzej; Zbytek, Blazej; Szczesniewski, Andrzej; Semak, Igor; Kaminski, Jan; Sweatman, Trevor; Wortsman, Jacobo

    2005-04-01

    The response to systemic stress is organized along the hypothalamic-pituitary-adrenal axis (HPA), whereas the response to a peripheral stress (solar radiation) is mediated by epidermal melanocytes (cells of neural crest origin) responsible for the pigmentary reaction. Melanocytes express proopiomelanocortin (POMC), corticotropin-releasing hormone (CRH), and CRH receptor-1 (CRH-R1) and can produce corticosterone. In the present study, incubation of normal epidermal melanocytes with CRH was found to trigger a functional cascade structured hierarchically and arranged along the same algorithm as in the HPA axis: CRH activation of CRH-R1 stimulated cAMP accumulation and increased POMC gene expression and production of ACTH. CRH and ACTH also enhanced production of cortisol and corticosterone, and cortisol production was also stimulated by progesterone. The chemical identity of the cortisol was confirmed by liquid chromatography-mass spectrometry (LC/MS2) with [corrected] mass spectrometry-mass spectrometry analyses. POMC gene silencing abolished the stimulatory effect of CRH on corticosteroid synthesis, indicating that this is indirect and mediated via production of ACTH. Thus the melanocyte response to CRH is highly organized along the same functional hierarchy as the HPA axis. This pattern demonstrates the fractal nature of the response to stress with similar activation sequence at the single-cell and whole body levels.

  6. Adrenal hemorrhage complicating ACTH therapy in Crohn's disease.

    PubMed

    Levin, T L; Morton, E

    1993-01-01

    Huge dose ACTH therapy is used in some severely ill patients with inflammatory bowel disease. We report a teenage girl with Crohn's disease who developed an acute abdomen following ACTH therapy. CT revealed the mass to be a hemorrhagic adrenal gland; the opposite adrenal gland was hypertrophied but without signs of hemorrhage.

  7. Corticotropin-releasing hormone, proopiomelanocortin, and glucocorticoid receptor gene expression in adrenocorticotropin-producing tumors in vitro.

    PubMed Central

    Suda, T; Tozawa, F; Dobashi, I; Horiba, N; Ohmori, N; Yamakado, M; Yamada, M; Demura, H

    1993-01-01

    To differentiate between ectopic ACTH syndrome and Cushing's disease, gene expression of corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), and glucocorticoid receptor was examined in 10 pituitary adenomas (Cushing's disease) and in 10 ectopic ACTH-producing tumors. CRH increased plasma ACTH levels in all patients with Cushing's disease and in five patients with ectopic ACTH syndrome whose tumors contained CRH and CRH mRNA. In five CRH nonresponders, CRH was not detected in tumors that contained no CRH mRNA or that contained only long-size CRH mRNA. Dexamethasone (Dex) decreased plasma ACTH levels in all patients with Cushing's disease and in three patients with ectopic ACTH-producing bronchial carcinoid. These tumors contained glucocorticoid receptor mRNA. CRH increased and Dex decreased ACTH release and POMC mRNA levels in pituitary adenoma and bronchial carcinoid cells. PMA increased POMC mRNA levels only in carcinoid cells. These results reveal characteristics of ectopic ACTH-producing tumors: long-size CRH mRNA and PMA-induced POMC gene expression. In addition, there are two ectopic ACTH syndrome subtypes: tumors containing ACTH with CRH (CRH responder) and tumors without CRH. Dex decreases ACTH release and POMC mRNA levels in some bronchial carcinoids. Therefore, CRH and Dex tests have limited usefulness in differentiating between Cushing's disease and ectopic ACTH syndrome. Images PMID:8254033

  8. Human and murine pituitary expression of leukemia inhibitory factor. Novel intrapituitary regulation of adrenocorticotropin hormone synthesis and secretion.

    PubMed Central

    Akita, S; Webster, J; Ren, S G; Takino, H; Said, J; Zand, O; Melmed, S

    1995-01-01

    Leukemia inhibitory factor (LIF) gene expression was detected in human fetal pituitary tissue by expression of LIF mRNA transcripts, protein immunocytochemistry, and immunoelectron microscopy. Fetal LIF immunoreactivity colocalized with 30% of ACTH-expressing cells, approximately 20% of somatotrophs, and approximately 15% of non-hormone-expressing cells. LIF was also strongly expressed in normal adult pituitary and in four growth hormone-producing and two ACTH-producing adenomas, but not in eight nonfunctioning pituitary tumors. Culture of fetal cells expressing surface LIF-binding sites demonstrated predominance of in vitro ACTH secretion as compared with other pituitary hormones. In AtT-20 murine cells, LIF (ED50 10 pM) stimulated basal proopiomelanocortin mRNA levels by 40% and corticotropin-releasing hormone-induced ACTH secretion (two- to threefold), as did oncostatin M (ED50 30 pM), a related peptide. ACTH responses were not further enhanced by both cytokines together, which is consistent with their shared receptor. Anti-LIF antiserum neutralized basal and LIF-induced ACTH secretion, suggesting autocrine regulation of ACTH by LIF. The results show that human pituitary cells express the LIF gene and LIF-binding sites, predominantly in corticotrophs. Pituitary LIF expression and LIF regulation of proopiomelanocortin and ACTH reflect an intrapituitary role for LIF in modulating early embryonic determination of specific human pituitary cells and as a paracrine or autocrine regulator of mature ACTH. Images PMID:7883977

  9. The effects of stress on plasma ACTH and corticosterone in young and aging pregnant rats and their fetuses

    SciTech Connect

    Erisman, S. ); Carnes, M. Univ. of Wisconsin, Madison ); Takahashi, L.K.; Lent, S.J. )

    1990-01-01

    Compared to younger rats, old rats exhibit prolonged elevations of plasma ACTH and corticosterone (CORT) in response to stress. In addition, CORT crosses the placenta. To investigate whether fetuses of older rats may be exposed to higher concentrations of CORT during development than fetuses of young rats, we compared the effects of stress on hypothalamic-pituitary-adrenal (HPA) axis function in young and aging pregnant rats and their 19-day-old fetuses. The plasma of the mothers and fetuses was assayed for ACTH and CORT by radioimmunoassay. Both young and aging pregnant rats showed a significant increase in plasma ACTH and CORT immediately after exposure to stress. However, aging rats had more prolonged elevation of ACTH and CORT than young rats. This suggests that, like old male rats, aging pregnant rats have an alteration in feedback inhibition of the HPA axis. Prolonged elevation of CORT was also seen in fetuses of aging mothers. These results have important implications concerning the effects of stress during pregnancy at different maternal ages, and for the potential deleterious consequences of prolonged prenatal elevation in stress hormones on the offspring of aging females.

  10. Bowel perforation complicating an ACTH-secreting phaeochromocytoma

    PubMed Central

    Flynn, Elise; Liu, Dorothy; Ekinci, Elif I; Farrell, Stephen; Zajac, Jeffrey D; De Luise, Mario; Seeman, Ego

    2016-01-01

    Summary ACTH-secreting phaeochromocytoma (ASP) is a rare cause of ACTH-dependent Cushing’s syndrome (CS). We report the case of a 63-year-old female presenting with CS secondary to an ASP complicated by bowel perforation. This case report highlights ASP as an uncommon but important cause of ectopic ACTH secretion (EAS). There have been 29 cases of ASP, all of which were unilateral and benign, but associated with significant complications. Patients presenting with ASP have the potential for cure with unilateral adrenalectomy. Given this promising prognosis if recognised, ASP should be considered in the diagnostic workup of ACTH-dependent CS. As this case demonstrates, gastrointestinal complications can arise from severe hypercortisolaemia associated with CS. Early medical and surgical intervention is imperative as mortality approaches 50% once bowel perforation occurs. Learning points Consider phaeochromocytoma in the diagnostic workup of ACTH-dependent CS; screen with plasma metanephrines or urinary catecholamines. Serial screening may be required if ACTH-secreting phaeochromocytoma is suspected, as absolute levels can be misleading. Early catecholamine receptor blockade and adrenal synthesis blockade may avoid the need for rescue bilateral adrenalectomy in ACTH-secreting phaeochromocytoma. Consider early medical or surgical management when gastrointestinal features are present in patients with CS, as bowel perforation due to severe hypercortisolaemia can occur and is associated with significant mortality. PMID:28203371

  11. Atrazine Does Not Induce Pica Behavior at Doses that Increase Hypothalamic-Pituitary-Adrenal Axis Activation and Cause Conditioned Taste Avoidance.

    EPA Science Inventory

    Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH), serum corticosterone (CORT) and progesterone. The mechanism for these effects is unknown. To tes...

  12. Pituitary gland

    MedlinePlus Videos and Cool Tools

    ... women; stimulates sperm production in men Prolactin - stimulates breast tissue in nursing mothers to produce milk ACTH (adrenocorticotropic hormone) - causes the adrenal glands to produce important substances that have properties similar ...

  13. The characteristics of the expression of heat shock proteins and COX-2 in the liver of hamsters infected with Clonorchis sinensis, and the change of endocrine hormones and cytokines.

    PubMed

    Choi, WonHyung; Chu, JongPhil

    2012-12-01

    The liver fluke Clonorchis sinensis (Digenea) is a high-risk parasite that causes serious diseases such as cirrhosis, carcinogenic liver damage and clonorchiasis in East Asia. This study was conducted to evaluate the relationship between stress/endocrine hormones and inflammation induced by infection as well as the expression of heat shock proteins (hsp-27, hsp-90), cox-2 and cytokines in the livers of hamsters infected with C. sinensis. The average body weight of infected hamsters decreased up to 25% compared with that of the control group, and bile duct hyperplasia with inflammation, liver fibrosis and hepatic necrosis were observed in C. sinensis-infected livers. The expression of hsp-27, hsp-90, and cox-2 was significantly increased in the livers of C. sinensis-infected hamsters compared with the control group. Moreover, the expression levels of inflammatory cytokines (IL-1beta, IL-2, TGF-beta2 and IFN-alpha1) were markedly increased in the livers of the infected group compared with those of the control group. Consistently, plasma IL-3 and IL-6 levels gradually increased during the infection period, and the concentration levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), corticosterone, and adrenocorticotropic hormone (ACTH) in C. sinensis-infected hamsters increased over 25%, compared with those of the uninfected normal group. These results demonstrate that C. sinensis infection may increase the expression of hsp27, hsp90 and cox-2 as well as it may cause periductal fibrosis, chronic inflammation and hepatic necrosis in the liver. Furthermore, the results indicate that C. sinensis infection induces not only stress-induced hormone imbalance but also the sustained secretion of inflammatory cytokines through chronic stress/stimuli.

  14. The increase of serum Bcl-2 concentration in moderate head injury outcome: The role of ACTH4-10Pro8-Gly9-Pro10

    PubMed Central

    Indharty, Rr Suzy

    2013-01-01

    Background: Traumatic brain injury (TBI) is one of the major causes of death and disability. Apoptosis after TBI contributes significantly to the final extent of tissue damage. The Bcl-2 family proteins are important apoptosis modulators which increased in injured neurons. Bcl-2 has shown an antiapoptotic effect in rats and mice. ACTH4-10Pro8-Gly9-Pro10 is a synthetic short fragment of ACTH devoid of hormonal effects and has neuromodulatory properties. ACTH4-10Pro8-Gly9-Pro10 has been shown to increase levels of Bcl-2 and BDNF in vitro as well as in vivo. It has been postulated that ACTH4-10Pro8-Gly9-Pro10 will result in improved clinical outcome and reduce hospital length of stay. The goal of this study is to compare the effect of standard therapy only with standard therapy and ACTH4-10Pro8-Gly9-Pro10, the increase of Bcl-2, and clinical outcome with reduction of hospital stay. Materials and Methods: Subjects of moderate head injury (MHI) with no indication of surgery were taken consecutively (n = 40) and separated into two groups: standard treatment only and standard treatment combined with ACTH4-10Pro8-Gly9-Pro10. Blood samples were taken on day 1 and day 5 from each subject for measurements of Bcl-2 concentration. Barthel Index and MMSE were measured, at discharge and hospital length of stay was noted. Results: Forty subjects have been involved in this study, three subjects died in the standard therapy group, and one subject in ACTH4-10Pro8-Gly9-Pro10 group. Bcl-2 serum level in standard therapy was 1.39 ± 0.75 ng/mL on day 1 and 1.48 ± 0.77 ng/mL on day 5. After treatment with ACTH4-10Pro8-Gly9-Pro10, Bcl-2 level was 1.39 ± 0.70 ng/mL on day 1 and 3.70 ± 1.02 ng/mL on day 5. The serum Bcl-2 concentration was significantly increased with ACTH4-10Pro8-Gly9-Pro10 therapy with shorter hospital length of stay (P < 0.05). Conclusion: ACTH4-10Pro8-Gly9-Pro10 increased serum Bcl-2 levels and reduced hospital length of stay significantly compared with standard

  15. ACTH stimulation test in the captive cheetah (Acinonyx jubatus).

    PubMed

    Köster, L S; Schoeman, J P; Meltzer, D G A

    2007-09-01

    Serum cortisol response was assessed in 8 captive cheetahs, of varying ages, after the intravenous administration of 500 microg of tetracosactide (Synacthen Depot, Novartis, Kempton Park) while maintained under general anaesthesia. In addition, 8 cheetahs were anaesthetised and given an equal volume of saline in order to establish baseline cortisol concentrations at similar stages of anaesthesia. A significant difference in the median cortisol concentration measured over time was found following ACTH administration in the ACTH group (P < 0.001). There was no difference between the median cortisol concentrations in the ACTH group at time-points 120, 150 and 180 min after ACTH stimulation (P = 0.867). Thus it appears appropriate to collect serum 120 to 180 min after tetracosactide administration to assess maximal stimulation of the adrenal in the cheetah. No statistically significant rise was seen in the anaesthetised control group following the injection of saline (P = 0.238).

  16. Evaluation of immune and stress status in harbour porpoises (Phocoena phocoena): can hormones and mRNA expression levels serve as indicators to assess stress?

    PubMed Central

    2013-01-01

    Background The harbour porpoise is exposed to increasing pressure caused by anthropogenic activities in its marine environment. Numerous offshore wind farms are planned or under construction in the North and Baltic Seas, which will increase underwater noise during both construction and operation. A better understanding of how anthropogenic impacts affect the behaviour, health, endocrinology, immunology and physiology of the animals is thus needed. The present study compares levels of stress hormones and mRNA expression of cytokines and acute-phase proteins in blood samples of harbour porpoises exposed to different levels of stress during handling, in rehabilitation or permanent human care. Free-ranging harbour porpoises, incidentally caught in pound nets in Denmark, were compared to harbour porpoises in rehabilitation at SOS Dolfijn in Harderwijk, the Netherlands, and individuals permanently kept in human care in the Dolfinarium Harderwijk and Fjord & Belt Kerteminde, Denmark. Blood samples were investigated for catecholamines, adrenaline, noradrenaline and dopamine, as well as for adrenocorticotropic hormone (ACTH), cortisol, metanephrine and normetanephrine. mRNA expression levels of relevant cell mediators (cytokines IL-10 and TNFα, acute-phase proteins haptoglobin and C-reactive protein and the heat shock protein HSP70) were measured using real-time PCR. Results Biomarker expression levels varied between free-ranging animals and porpoises in human care. Hormone and cytokine ranges showed correlations to each other and to the health status of investigated harbour porpoises. Hormone concentrations were higher in free-ranging harbour porpoises than in animals in human care. Adrenaline can be used as a parameter for the initial reaction to acute stress situations; noradrenaline, dopamine, ACTH and cortisol are more likely indicators for the following minutes of acute stress. There is evidence for different correlations between production of normetanephrine

  17. Mid-gut ACTH-secreting neuroendocrine tumor unmasked with 18F-dihydroxyphenylalanine-positron emission tomography

    PubMed Central

    Gomez, Fulgencio; Prior, John O; Boubaker, Ariane; Matter, Maurice; Monti, Matteo; Pu, Yan; Pitteloud, Nelly; Portmann, Luc

    2015-01-01

    Summary Ectopic ACTH Cushing's syndrome (EAS) is often caused by neuroendocrine tumors (NETs) of lungs, pancreas, thymus, and other less frequent locations. Localizing the source of ACTH can be challenging. A 64-year-old man presented with rapidly progressing fatigue, muscular weakness, and dyspnea. He was in poor condition and showed facial redness, proximal amyotrophy, and bruises. Laboratory disclosed hypokalemia, metabolic alkalosis, and markedly elevated ACTH and cortisol levels. Pituitary was normal on magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus blood sampling with corticotropin-releasing hormone stimulation showed no significant central-to-periphery gradient of ACTH. Head and neck, thoracic and abdominal computerized tomography (CT), MRI, somatostatin receptor scintigraphy (SSRS), and 18F-deoxyglucose-positron emission tomography (FDG-PET) failed to identify the primary tumor. 18F-dihydroxyphenylalanine (F-DOPA)-PET/CT unveiled a 20-mm nodule in the jejunum and a metastatic lymph node. Segmental jejunum resection showed two adjacent NETs, measuring 2.0 and 0.5 cm with a peritoneal metastasis. The largest tumor expressed ACTH in 30% of cells. Following surgery, after a transient adrenal insufficiency, ACTH and cortisol levels returned to normal values and remain normal over a follow-up of 26 months. Small mid-gut NETs are difficult to localize on CT or MRI, and require metabolic imaging. Owing to low mitotic activity, NETs are generally poor candidates for FDG-PET, whereas SSRS shows poor sensitivity in EAS due to intrinsically low tumor concentration of type-2 somatostatin receptors (SST2) or to receptor down regulation by excess cortisol. However, F-DOPA-PET, which is related to amine precursor uptake by NETs, has been reported to have high positive predictive value for occult EAS despite low sensitivity, and constitutes a useful alternative to more conventional methods of tumor localization. Learning points Uncontrolled high

  18. Therapeutic Effects of Pre-Gelatinized Maca (Lepidium Peruvianum Chacon) used as a Non-Hormonal Alternative to HRT in Perimenopausal Women - Clinical Pilot Study

    PubMed Central

    Meissner, H. O.; Reich-Bilinska, H.; Mscisz, A.; Kedzia, B.

    2006-01-01

    Background: Roots of cruciferous plant Lepidium peruvianum Chacon cultivated in high plateaus of Andes and known under its common name Maca, have been traditionally-used as an energizing vegetable with therapeutic properties for both men and women. Maca has been recognized by natives of Peru as herbal remedy helping to treat conditions affecting menopausal women. Objective: The effects of Pre-Gelatinized Organic Maca (Maca-GO) on quantitative physiological responses and alleviation of symptoms contributing to menopausal discomfort in perimenopausal women was examined. Methods: In this, four months, double blind, crossover, randomized pilot trial, monthly measurements of the following blood serum constituents were taken: Estrogen (E2), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and Progesterone (PGS), Cortisol (CT), Adrenocorticotropic Hormone (ACTH), Thyroid Hormones (TSH, T3, T4), minerals (Ca, K, Fe) and lipid profile (Triglicerides, Total Cholesterol, LDL, HDL). In monthly interviews conducted by gynecologist, body weight and blood pressure were registered and Menopausal Index according to Kupperman’s was determined. Toxicity of Maca -GO determined on rats showed its safe use at the level of 7.5mg/kg body weight. A group of 20 women (aged 41-50 years), who fulfilled criteria of being in perimenopausal stage (E2 above 40pg/ml and FSH below 30IU/ml), were randomly allocated to two even groups, one receiving for two months Maca-GO and the other Placebo capsules followed by a crossover with treatment change for another two months period. All participants signed informed consent to participate. Two 500mg hard capsules with Maca-GO or Placebo were self-administered by participants twice daily with meals (total 2g/day). Results: Two months administration of Maca-GO significantly alleviated symptoms of discomfort observed in majority of women involved in the study (74%-87%) as assessed by Kupperman’s Menopausal index. This was associated with

  19. Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (I) Biochemical and Pharmacodynamic Study on Maca using Clinical Laboratory Model on Ovariectomized Rats.

    PubMed

    Meissner, H O; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Mscisz, A; Kedzia, B; Lowicka, A; Reich-Bilinska, H; Kapczynski, W; Barchia, I

    2006-09-01

    Ovariectomized rats were used in a model laboratory study to examine biochemical and pharmacodynamic effects of pre-gelatinized organic preparation of Lepidium peruvianum Chacon (Maca-GO). Biochemical and Pharmacodynamic effects of Maca-GO (250 mg Maca-GO per kg body weight (bw) administered by intubation twice daily) were assessed in a 28 day model laboratory study on ovariectomized (by laparoscopy) Wistar rats with pharmacodynamic tests performed at the conclusion of the trial followed by blood collection for morphology and biochemical tests. Toxicity of Maca-GO used in the study was determined in bioassay on mice and rats. Anti-depressive function (Porsolt's test) and anxiolytic sedative and cognitive effects (using elevated-plus maze, locomotor activity and passive avoidance tests) were assessed against control (laparotomized female rats with intact ovaries). In addition to blood morphology, the following blood serum constituents were analyzed: Estrogen (E2), Progesterone (PGS), Cortisol (CT), Adrenocorticotropic Hormone (ACTH), Thyroid Hormones (TSH, T3, and T4), Iron (Fe) and lipid profile (Triglycerides, Total Cholesterol, LDL, HDL). Analytically-determined non-toxic status of Maca-GO was confirmed in bioassays when applied to mice and rats at levels of 0.5 and up to 15mg/kg bw which shows it safe use in humans with the LD50>15 mg/kg bw. Maca-GO showed a distinctive, (P<0.05) antidepressant-like and sedative effect in ovariectomized rats only, while there was no anxiolytic activity nor disturbance of cognitive function observed in both, test and control animals. Observed in this study balancing effect of Maca-GO on sex hormone levels show its potential as a safe preparation for use in correcting physiological symptoms characteristic in postmenopausal stage with an indication of potentially even more value for its use in pre-menopausal women.

  20. Effects of Chronic ACTH Excess on Human Adrenal Cortex

    PubMed Central

    Bertagna, Xavier

    2017-01-01

    Chronic ACTH excess leads to chronic cortisol excess, without escape phenomenon, resulting in Cushing’s syndrome. Excess adrenal androgens also occur: in females, they will overcompensate the gonadotrophic loss, inducing high testosterone; in males, they will not compensate it, inducing low testosterone. Chronic ACTH excess leads to chronic adrenal mineralocorticoid excess and low aldosterone levels: after an acute rise, aldosterone plasma levels resume low values after a few days when ACTH is prolonged. Two other mineralocorticoids in man, cortisol and 11 deoxycorticosterone (DOC), at the zona fasciculata, will not escape the long-term effect of chronic ACTH excess and their secretion rates will remain elevated in parallel. Over all, the concomitant rise in cortisol and 11 DOC will more than compensate the loss of aldosterone, and eventually create a state of chronic mineralocorticoid excess, best evidenced by the accompanying suppression of the renin plasma levels, a further contribution to the suppression of aldosterone secretion. Prolonged in vivo stimulation with ACTH leads to an increase in total adrenal protein and RNA synthesis. Cell proliferation is indicated by an increase in total DNA the resulting adrenocortical hyperplasia participates in the amplified response of the chronically stimulated gland, and the weight of each gland can be greatly increased. The growth-stimulatory effect of ACTH in vivo most likely proceeds through the activation of a local and complex network of autocrine growth factors and their own receptors; a number of compounds, including non-ACTH proopiomelanocortin peptides such as γ3-MSH, have been shown to exert some adrenocortical growth effect. PMID:28337175

  1. Kaposi sarcoma secondary to endogenous adrenocorticotropic hormone-dependent Cushing syndrome.

    PubMed

    Mayor-Ibarguren, A; Roldán-Puchalt, M C; Sancho-Bueso, T; Pérez-López, C; Álvarez-Linera, J; Frutos, R; Álvarez-Escolá, C; Regojo-Zapata, R; Beato-Merino, M J; Herranz-Pinto, P; Lecumberri, B

    2016-06-01

    Kaposi sarcoma (KS) is an angioproliferative tumour that develops as a result of an infection by human herpesvirus 8, which is considered a necessary cause but not sufficient. Other factors - genetic, immunological and environmental - might play a role in the development of the disease. We report a case of KS secondary to endogenous Cushing syndrome (ECS) due to a pituitary adenoma, an association that has been reported only once. We also conducted a search through the Medline and PubMed databases for cases involving KS and ECS, finding only three additional cases that shared common clinical and prognostic features with ours. ECS might favour the development of KS due to immunosuppression. Dermatologists and other clinicians should be aware of this association, as it might be an underdiagnosed condition. It also has an important impact on the management of KS, and based on this review it relies on a good prognosis when ECS is well controlled.

  2. Brain shrinkage and subdural effusion associated with ACTH administration.

    PubMed

    Satoh, J; Takeshige, H; Hara, H; Fukuyama, Y

    1982-01-01

    Sequential computed tomographic (CT) studies of 11 patients (aged five months to seven years) with intractable epilepsy treated with synthetic ACTH-Z showed brain shrinkage in all cases. Brain shrinkage started to appear on daily ACTH injections for seven days, reached the maximum within four weeks of administration (14 injections every day and then 7 injections every other day), and almost returned to the original status in seven out of nine cases which were followed up for one to three months after the therapy. The subjects aged less than two years showed more remarkable brain shrinkage than did those aged more than five years. Furthermore, two other cases were complicated by subdural effusion after ACTH therapy. It is the authors' assumption that both of these phenomena are caused by the high concentration of corticosteroid through a change of the water and electrolyte contents in the brain.

  3. Reintoxication: the release of fat-stored Δ9-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure

    PubMed Central

    Gunasekaran, N; Long, LE; Dawson, BL; Hansen, GH; Richardson, DP; Li, KM; Arnold, JC; McGregor, IS

    2009-01-01

    Background and purpose: Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, accumulates in adipose tissue where it is stored for long periods of time. Here we investigated whether conditions that promote lipolysis can liberate THC from adipocytes to yield increased blood levels of THC. Experimental approach: In vitro studies involved freshly isolated rat adipocytes that were incubated with THC before exposure to the lipolytic agent adrenocorticotrophic hormone (ACTH). A complementary in vivo approach examined the effects of both food deprivation and ACTH on blood levels of THC in rats that had been repeatedly injected with THC (10 mg·kg−1) for 10 consecutive days. Lipolysis promoted by ACTH or food deprivation was indexed by measurement of glycerol levels. Key results: ACTH increased THC levels in the medium of THC-pretreated adipocytes in vitro. ACTH also enhanced THC release from adipocytes in vitro when taken from rats repeatedly pretreated with THC in vivo. Finally, in vivo ACTH exposure and 24 h food deprivation both enhanced the levels of THC and its metabolite, (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in the blood of rats that had been pre-exposed to repeated THC injections. Conclusions and implications: The present study shows that lipolysis enhances the release of THC from fat stores back into blood. This suggests the likelihood of ‘reintoxication’ whereby food deprivation or stress may raise blood THC levels in animals chronically exposed to the drug. Further research will need to confirm whether this can lead to functional effects, such as impaired cognitive function or ‘flashbacks’. PMID:19681888

  4. Magnetic resonance imaging in infantile spasms: effects of hormonal therapy.

    PubMed

    Konishi, Y; Yasujima, M; Kuriyama, M; Konishi, K; Hayakawa, K; Fujii, Y; Ishii, Y; Sudo, M

    1992-01-01

    Magnetic resonance imaging (MRI) was performed on five patients with infantile spasms who were treated with relatively low doses of adrenocorticotrophic hormone (ACTH) to study the extent of brain shrinkage induced by ACTH therapy. MRI prior to ACTH therapy revealed periventricular hyperintensity (PVH) areas and poor myelination in four patients. In one case, MRI performed 2 days after initiation of ACTH therapy also showed PVH and poor myelination. Brain shrinkage was observed 2 weeks after initiation of ACTH therapy. The most impressive follow-up finding upon MRI was the decrease in PVH found in four patients. The differentiation between myelinated white matter and surrounding cortex became poorer in three cases. Cortical atrophy progressed in all patients but ventricular dilation progressed in only one patient. At the end of ACTH therapy, ventricular dilation progressed in all cases. These findings suggest that loss of water not only from periventricular white matter but also from cortex is the main etiological factor of brain shrinkage induced by ACTH.

  5. Cerebral blood flow and brain shrinkage seen on CT during ACTH therapy.

    PubMed

    Futagi, Y; Abe, J; Kawahigashi, K

    1986-01-01

    By means of the Doppler ultrasound method, the cerebral blood flow (CBF) was assessed in 21 children with epilepsy undergoing treatment with adrenocorticotrophic hormone (ACTH). The maximum reduction in the internal carotid velocity, as an index of CBF during therapy, was about 35 percent compared with the values before therapy. Furthermore, sequential computed tomography (CT) examinations of the same subjects were performed to evaluate the change in the area of the intracranial brain parenchyma during therapy. The maximum reduction in the parenchymal area during therapy was about 10 percent. This corresponds to a 20 percent reduction in CBF according to Poiseuille's law, however, the remaining reduction in CBF demonstrated by velocity measurement cannot be explained only by that mechanical vascular factor. From these findings, it is concluded that in order to elucidate the mechanism of the CBF reduction, physiological factors such as changes in metabolism during therapy should also be evaluated in addition to the mechanical and physical causes.

  6. Effect of high-dose total body irradiation on ACTH, corticosterone, and catecholamines in the rat.

    PubMed

    Cohen, Eric P; Bruder, Eric D; Cullinan, William E; Ziegler, Dana; Raff, Hershel

    2011-01-01

    Total body irradiation (TBI) or partial body irradiation is a distinct risk of accidental, wartime, or terrorist events. Total body irradiation is also used as conditioning therapy before hematopoietic stem cell transplantation. This therapy can result in injury to multiple tissues and might result in death as a result of multiorgan failure. The hypothalamic-pituitary-adrenal (HPA) axis could play a causative role in those injuries, in addition to being activated under conditions of stress. In a rat model of TBI, we have established that radiation nephropathy is a significant lethal complication, which is caused by hypertension and uremia. The current study assessed HPA axis function in rats undergoing TBI. Using a head-shielded model of TBI, we found an enhanced response to corticotropin-releasing hormone (CRH) in vitro in pituitaries from irradiated compared with nonirradiated rats at both 8 and 70 days after 10-Gy single fraction TBI. At 70, but not 8 days, plasma adrenocorticotrophic hormone (ACTH) and corticosterone levels were increased significantly in irradiated compared with nonirradiated rats. Plasma aldosterone was not affected by TBI at either time point, whereas plasma renin activity was decreased in irradiated rats at 8 days. Basal and stimulated adrenal steroid synthesis in vitro was not affected by TBI. In addition, plasma epinephrine was decreased at 70 days after TBI. The hypothalamic expression of CRH messenger RNA (mRNA) and hippocampal expression of glucocorticoid receptor mRNA were unchanged by irradiation. We conclude that the hypertension of radiation nephropathy is not aldosterone or catecholamine-dependent but that there is an abscopal activation of the HPA axis after 10 Gy TBI. This activation was attributable at least partially to enhanced pituitary ACTH production.

  7. Expression of receptors for luteinizing hormone, gastric-inhibitory polypeptide, and vasopressin in normal adrenal glands and cortisol-secreting adrenocortical tumors in dogs.

    PubMed

    Galac, S; Kars, V J; Klarenbeek, S; Teerds, K J; Mol, J A; Kooistra, H S

    2010-07-01

    Hypercortisolism caused by an adrenocortical tumor (AT) results from adrenocorticotropic hormone (ACTH)-independent hypersecretion of glucocorticoids. Studies in humans demonstrate that steroidogenesis in ATs may be stimulated by ectopic or overexpressed eutopic G protein-coupled receptors. We report on a screening of 23 surgically removed, cortisol-secreting ATs for the expression of receptors for luteinizing hormone (LH), gastric-inhibitory polypeptide (GIP), and vasopressin (V(1a), V(1b), and V(2)). Normal adrenal glands served as control tissues. Abundance of mRNA for these receptors was quantified using quantitative polymerase chain reaction (QPCR), and the presence and localization of these receptors were determined by immunohistochemistry. In both normal adrenal glands and ATs, mRNA encoding for all receptors was present, although the expression abundance of the V(1b) receptor was very low. The mRNA expression abundance for GIP and V(2) receptors in ATs were significantly lower (0.03 and 0.01, respectively) than in normal adrenal glands. The zona fasciculata of normal adrenal glands stained immunonegative for the GIP receptor. In contrast, islands of GIP receptor-immunopositive cells were detected in about half of the ATs. The zona fasciculata of both normal adrenal glands and AT tissue were immunopositive for LH receptor; in ATs in a homogenous or heterogenous pattern. In normal adrenal glands, no immunolabeling for V(1b)R and V(2) receptor was present, but in ATs, V(2) receptor-immunopositive cells were detected. In conclusion, QPCR analysis did not reveal overexpression of LH, GIP, V(1a), V(1b), or V(2) receptors in the ATs. However, the ectopic expression of GIP and V(2) receptor proteins in tumorous zona fasciculata tissue may play a role in the pathogenesis of canine cortisol-secreting ATs.

  8. ACTH and. cap alpha. -melanotropin in central temperature control

    SciTech Connect

    Lipton, J.M.; Glyn, J.R.; Zimmer, J.A.

    1981-11-01

    Adrenocorticotropin (ACTH) and ..cap alpha..-melanotropin (..cap alpha..-MSH) occur in brain tissue known to be important to temperature control. These peptides cause hypothermia if they are injected centrally in sufficient doses, but they do not act on the central set point of temperature control. Instead they appear to inhibit central pathways for heat conservation and production. In addition to their hypothermic capability, these peptides are antipyretic when given centrally in doses that have no effect on normal body temperature. ACTH has previously been associated with fever reduction in both clinical and experimental studies, and it may be that endogenous central ACTH is important for limitation of maximal fever. The hypothermic and antipyretic effects of ACTH do not depend on stimulation of the adrenal cortex because they are also observed in adrenalectomized rabbits. Nor is the antipyretic effect limited to the rabbit inasmuch as a comparable effect has been demonstrated in the squirrel monkey. The two peptides may be involved in central mediation of normal thermoregulation and fever, perhaps limiting the febrile response and other rises in body temperature by acting as neurotransmitters or neuromodulators in central thermoregulatory pathways.

  9. Aberrant expression of glucagon receptors in adrenal glands of a patient with Cushing's syndrome and ACTH-independent macronodular adrenal hyperplasia.

    PubMed

    de Miguel, Valeria; Redal, María Ana; Viale, María Lorena; Kahan, Mariano; Glerean, Mariela; Beskow, Axel; Fainstein Day, Patricia

    2010-01-01

    Adrenocorticotropin (ACTH) independent bilateral macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome, characterized by bilateral adrenal lesions and excess cortisol production despite ACTH suppression. Cortisol synthesis is produced in response to abnormal activation of G-protein-coupled receptors, such as gastric inhibitory peptide, vasopressin, beta adrenergic agonists, LH/hCG and serotonin receptors. The aim of this study was to analyze the expression of glucagon receptors in adrenal glands from an AIMAH patient. A patient with ACTH-independent Cushing's syndrome and bilateral macronodular adrenal hyperplasia was screened for altered activation of adrenal receptors by physiological (mixed meal) and pharmacological (gonadotrophin releasing hormone, ACTH and glucagon) tests. The results showed abnormally high levels of serum cortisol after stimulation with glucagon. Hypercortisolism was successfully managed with ketoconazole treatment. Interestingly, a 4-month treatment with a somatostatin analogue (octreotide) was also able to reduce cortisol secretion. Finally, Cushing's syndrome was cured after bilateral adrenalectomy. Abnormal mRNA expression for glucagon receptor in the patient's adrenal glands was observed by Real-Time PCR procedure. These results strongly suggest that the mechanism of AIMAH causing Cushing's syndrome in this case involves the illicit activation of adrenal glucagon receptors. This is the first case reported of AIMAH associated with ectopic glucagon receptors.

  10. Effects of vitamin C and vitamin E on lipid peroxidation status, serum hormone, metabolite, and mineral concentrations of Japanese quails reared under heat stress (34 degrees C).

    PubMed

    Sahin, Kazim; Kucuk, Osman; Sahin, Nurhan; Sari, Mustafa

    2002-03-01

    This study was conducted to determine the effects of dietary vitamin C (L-ascorbic acid) and vitamin E (alpha-tocopherol acetate) on lipid peroxidation status measured as MDA and serum triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), as well as some other serum metabolite and mineral concentrations of Japanese quails reared under heat stress (34 degrees C). One hundred-eighty 10-day-old Japanese quails were randomly assigned to six treatment groups, three replicates of 10 birds each. Using a 2 x 3 factorial design, the birds received two levels of vitamin C (100 and 200 mg/kg of diet) or three levels of vitamin E (125, 250, or 500 mg/kg of diet). Greater dietary vitamin E and vitamin C resulted in a greater serum T3, T4, and TSH (p = 0.001), but lower ACTH (p = 0.001) concentrations. Serum concentrations of T4 and TSH increased to a greater extent by increasing dietary vitamin C when greater vitamin E levels were fed (interaction, p = 0.001). Serum glucose, urea, triglycerides, and cholesterol concentrations decreased (p = 0.001), while protein and albumin concentrations increased (p = 0.001) when both dietary vitamin C and vitamin E were increased. Serum activities of SGOT and SGPT were not influenced by dietary vitamin C and vitamin E (p > 0.43). However, serum activity of AP increased (p = 0.001) by increasing both dietary vitamin C and vitamin E. Increasing both dietary vitamin C and vitamin E caused an increase in serum concentrations of Ca, P, K (p = 0.001), Fe, and Zn (p = 0.01) but a decrease in serum concentrations of Na (p = 0.001) and Cu (p = 0.01). Interactions between vitamin C and vitamin E were detected for Ca, P, Na, and K (p = 0.001). Greater dietary vitamin C and vitamin E resulted in a greater serum and liver vitamin E, C, and A (p < or = 0.05), but lower MDA (p = 0.001) concentrations. Results of the present study conclude that supplementing a combination of dietary vitamin C (200 mg

  11. Testosterone, estradiol, ACTH and musical, spatial and verbal performance.

    PubMed

    Hassler, M; Gupta, D; Wollmann, H

    1992-01-01

    Testosterone, estradiol, and ACTH were determined in blood serum of 26 healthy males aged 19.16 and of 25 healthy females aged 18.77 years on average, and results were correlated with test scores of three spatial tests, a verbal fluency measure, and a test measuring general musical ability. In addition, hemispheric lateralization for verbal material and handedness was assessed. While testosterone and estradiol alone were not significantly related to any of the cognitive or musical tests, testosterone/estradiol ratio was significantly negatively correlated with spatial tests, and ACTH was significantly positively correlated with spatial and musical tests. Correlations were stronger in females than in males. The laterality index was significantly negatively correlated with testosterone in males indicating that right hemisphere involvement in verbal processing was associated with high testosterone levels.

  12. ACTH-like peptides increase pain sensitivity and antagonize opiate analgesia

    NASA Technical Reports Server (NTRS)

    Heybach, J. P.; Vernikos, J.

    1981-01-01

    The role of the pituitary and of ACTH in pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 C. Hypophysectomy reduced pain sensitivity, and this effect was reversed by the intracerebroventricular (ICV) injection of the opiate antagonist naloxone. Similarly, the analgesia produced by a dose of morphine was antagonized by the administration of ACTH or alpha-MSH. The peripheral injection of ACTH or alpha-MSH in normal rats did not increase pain sensitivity. However, ACTH administered ICV increased pain sensivity within 10 min. The results indicate that the pituitary is the source of an endogenous opiate antagonist and hyperalgesic factor and that this factor is ACTH or an ACTH-like peptide. This activity resides in the N-terminal portion of the ACTH molecule since ACTH sub 4-10 is not active in this respect, nor does this activity require a free N-terminal serine since alpha-MSH appears to be almost as potent as the ACTH sub 1-24 peptide. It is concluded that ACTH-like peptides of pituitary origin act as endogenous hyperalgesic and opiate antagonistic factors.

  13. Corticotropin (ACTH) regulates alternative RNA splicing in Y1 mouse adrenocortical tumor cells.

    PubMed

    Schimmer, Bernard P; Cordova, Martha

    2015-06-15

    The stimulatory effect of ACTH on gene expression is well documented and is thought to be a major mechanism by which ACTH maintains the functional and structural integrity of the gland. Previously, we showed that ACTH regulates the accumulation of over 1200 transcripts in Y1 adrenal cells, including a cluster with functions in alternative splicing of RNA. On this basis, we postulated that some of the effects of ACTH on the transcription landscape of Y1 cells are mediated by alternative splicing. In this study, we demonstrate that ACTH regulates the alternative splicing of four transcripts - Gnas, Cd151, Dab2 and Tia1. Inasmuch as alternative splicing potentially affects transcripts from more than two-thirds of the mouse genome, we suggest that these findings are representative of a genome-wide effect of ACTH that impacts on the mRNA and protein composition of the adrenal cortex.

  14. Investigating Genomic Mechanisms of Treatment Resistance in Castration Resistant Prostate Cancer

    DTIC Science & Technology

    2013-05-01

    Sensitive Prostate Cancer”. Oncol. Rep. 2012 Jan;27(1):3-9. 4. Friedlander TW, Ryan CJ. Editorial Comment on “ Adrenocorticotropic hormone (ACTH...warranting an elevated dose (1000mg twice daily). Blood is currently being collected for serum hormone levels, SNPs in androgen synthesis genes...Bladder Cancer, genomics, microarrays, pharmacogenetics, circulating tumor cells, androgen biosynthesis inhibitors, hormonal therapy, clinical trials

  15. Transient brain shrinkage in infantile spasms after ACTH treatment. Report of two cases.

    PubMed

    Maekawa, K; Ohta, H; Tamai, I

    1980-02-01

    This is the report of two cases of infantile spasms, manifesting transient brain shrinkage in computerized tomography (CT) after ACTH treatment. ACTH was given for 8 weeks to a 8-months-old Japanese girl with infantile spasms. First CT performed at 2 weeks after the final ACTH injection, displayed moderate brain shrinkage. Second CT at 4 months showed marked diminution of the shrinkage. ACTH was also given for 8 weeks to a 14 months old Japanese boy with infantile spasms. First CT, just before ACTH treatment, showed mild cortical atrophy, the second at 7 days after the final ACTH injection revealed marked brain shrinkage and moderate ventricular dilatation, and the third at 2 months, disclosed mild improvement of the shrinkage. ACTH or corticoateroid has widespread effects on the developing nervous system. In animal experiments, ACTH or steroids interfere with brain growth of young rats. CT findings of transient brain shrinkage in a child with infantile spasms might suggest that intensive treatment with ACTH or steroids in infancy interferes with brain growth as seen in the results of animal experiments.

  16. Comparative study of analgesic potency of ACTH4-10 fragment and its analog semax.

    PubMed

    Ivanova, D M; Levitskaya, N G; Andreeva, L A; Kamenskii, A A; Myasoedov, N F

    2007-01-01

    The effects of ACTH4-10 fragment and its analog semax on nociception were examined on various animal models. ACTH4-10 in a dose of 0.5 mg/kg decreased nociception in rats during hindpaw compression test and in mice subjected to acetic acid writhing test. Lower doses of ACTH4-10 produced no analgesic effect. Semax (0.015-0.500 mg/kg) decreased pain sensitivity in all experimental models. Hence, the substitution of three C-terminal amino acid residues in ACTH4-10 for Pro-Gly-Pro sequence augmented the analgesic potency of the peptide after its peripheral injection.

  17. The adrenocortical response of greater sage grouse (Centrocercus urophasianus) to capture, ACTH injection, and confinement, as measured in fecal samples

    USGS Publications Warehouse

    Jankowski, M.D.; Wittwer, D.J.; Heisey, D.M.; Franson, J. Christian; Hofmeister, Erik K.

    2009-01-01

    Investigators of wildlife populations often utilize demographic indicators to understand the relationship between habitat characteristics and population viability. Assessments of corticosterone may enable earlier detection of populations at risk of decline because physiological adjustments to habitat disturbance occur before reproductive diminutions. Noninvasive methods to accomplish these assesments are important in species of concern, such as the greater sage grouse (GRSG). Therefore, we validated a radioimmunoassay that measures immunoreactive corticosterone metabolites (ICM) in fecal samples and used it to characterize the adrenocortical response of 15 GRSG exposed to capture, intravenous injection of 50 IU/kg adrenocorticotrophic hormone (ACTH) or saline, and 22 h of confinement. Those animals injected with ACTH exhibited a more sustained (P = 0.0139) and less variable (P = 0.0012) response than those injected with saline, indicating different levels of adrenocortical activity. We also found that potential field-collection protocols of fecal samples did not alter ICM concentrations: samples held at 4??C for up to 16 h contained similar levels of ICM as those frozen (-20??C) immediately. This study demonstrates a multiphasic adrenocortical response that varied with the level of stimulation and indicates that the assay used to measure this phenomenon is applicable for studies of wild GRSG. ?? 2009 by The University of Chicago. All rights reserved.

  18. Hormone levels

    MedlinePlus

    Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

  19. Plasma adrenocorticotropin (ACTH) concentrations and clinical response in horses treated for equine Cushing's disease with cyproheptadine or pergolide.

    PubMed

    Perkins, G A; Lamb, S; Erb, H N; Schanbacher, B; Nydam, D V; Divers, T J

    2002-11-01

    Plasma ACTH levels have been variable in horses with a positive clinical response for therapy for equine Cushing's Disease (ECD). Therefore, our purpose was to determine the value of monitoring plasma adrenocorticotropin (ACTH) levels during treatment of equine Cushing's disease (ECD) with either cyproheptadine (n = 32) or pergolide (n = 10). First, we validated the chemiluminescent ACTH assay (specificity, precision, accuracy, intra-assay and interassay variations) and tested methods of handling the whole blood from the time of collection to when the ACTH was assayed. The sensitivity and specificity of high plasma ACTH levels for detecting ECD was determined in a retrospective study on hospitalised horses (n = 68). Surveys were sent to veterinarians who submitted equine ACTH levels that were high initially and had at least 2 ACTH samples to determine the value of monitoring ACTH levels during therapy of ECD. The ACTH chemiluminescent assay was valid. The ACTH was stable when whole blood was collected and held in plastic tubes for 8 h before separating the plasma. The sensitivity and specificity of plasma ACTH levels for detecting ECD were 84% (n = 19,95% CI 60,97) and 78% (n = 49,95% CI 63,88), respectively. Treated horses generally showed a decrease in plasma ACTH. Plasma ACTH levels may be helpful when monitoring therapy of ECD, although improvement in clinical signs should be considered most important. There were no differences between cyproheptadine and pergolide in terms of improvements in any of the clinical signs.

  20. Hormone production by cultures of small-cell carcinoma of the lung.

    PubMed

    Sorenson, G D; Pettengill, O S; Brinck-Johnsen, T; Cate, C C; Maurer, L H

    1981-03-15

    Continuous cell lines have been established from a variety of biopsy and postmortem species of tumor from patients with small-cell carcinoma of the lung (SCCL) and have been maintained over several years. The medium from the cultures has been assayed for peptide, glycoprotein, and steroid hormones. Significant amounts of 14 hormones including calcitonin, adrenocorticotropin (ACTH), parathormone, luteinizing hormone, chorionic gonadotropin, glucagon, growth hormone, somatostatin, prolactin, beta-endorpin, lipotropin, oxytocin-neurophysin, vasopressin-neurophysin, and estradiol have been demonstrated. Up to ten different hormones have been produced by a single cell line. Most produce ACTH and all evaluated so far produce estradiol. These studies indicate that cells from SCCL have a potential for producing a wide variety of hormones and that this characteristic can be maintained for prolonged periods of culture in vitro.

  1. Effects of ghrelin, GH-releasing peptide-6 (GHRP-6) and GHRH on GH, ACTH and cortisol release in hyperthyroidism before and after treatment.

    PubMed

    Molica, Patricia; Nascif, Sergio Oliva; Correa-Silva, Silvia Regina; de Sá, Larissa Bianca Paiva Cunha; Vieira, José Gilberto Henriques; Lengyel, Ana-Maria Judith

    2010-12-01

    In thyrotoxicosis GH responses to stimuli are diminished and the hypothalamic-pituitary-adrenal axis is hyperactive. There are no data on ghrelin or GHRP-6-induced GH, ACTH and cortisol release in treated hyperthyroidism. We, therefore, evaluated these responses in 10 thyrotoxic patients before treatment and in 7 of them after treatment. GHRH-induced GH release was also studied. Peak GH (μg/L; mean ± SE) values after ghrelin (22.6 ± 3.9), GHRP-6 (13.8 ± 2.3) and GHRH (4.9 ± 0.9) were lower in hyperthyroidism before treatment compared to controls (ghrelin: 67.6 ± 19.3; GHRP-6: 25.4 ± 2.7; GHRH: 12.2 ± 2.8) and did not change after 6 months of euthyroidism (ghrelin: 32.7 ± 4.7; GHRP-6: 15.6 ± 3.6; GHRH: 7.4 ± 2.3), although GH responses to all peptides increased in ~50% of the patients. In thyrotoxicosis before treatment ACTH response to ghrelin was two fold higher (107.4 ± 26.3) than those of controls (54.9 ± 10.3), although not significantly. ACTH response to GHRP-6 was similar in both groups (hyperthyroid: 44.7 ± 9.0; controls: 31.3 ± 7.9). There was a trend to a decreased ACTH response to ghrelin after 3 months of euthyroidism (35.6 ± 5.3; P = 0.052), but after 6 months this decrease was non-significant (50.7 ± 14.0). After 3 months ACTH response to GHRP-6 decreased significantly (20.4 ± 4.2), with no further changes. In hyperthyroidism before treatment, peak cortisol (μg/dL) responses to ghrelin (18.2 ± 1.2) and GHRP-6 (15.9 ± 1.4) were comparable to controls (ghrelin: 16.4 ± 1.6; GHRP-6: 13.5 ± 0.9) and no changes were seen after treatment. Our results suggest that the pathways of GH release after ghrelin/GHRP-6 and GHRH are similarly affected by thyroid hormone excess and hypothalamic mechanisms of ACTH release modulated by ghrelin/GHSs may be activated in this situation.

  2. Use of radioguided surgery with [111In]-pentetreotide in the management of an ACTH-secreting bronchial carcinoid causing ectopic Cushing's syndrome.

    PubMed

    Grossrubatscher, E; Vignati, F; Dalino, P; Possa, M; Belloni, P A; Vanzulli, A; Bramerio, M; Marocchi, A; Rossetti, O; Zurleni, F; Loli, P

    2005-01-01

    Intraoperative [111In]-pentetreotide scintigraphy with a hand-held gamma detector probe has recently been proposed to increase the intraoperative detection rate of small neuroendocrine tumors and their metastases. We report a case of a 28-yr-old woman with ectopic Cushing's syndrome due to an ACTH-secreting bronchial carcinoid, in whom the use of radioguided surgery improved disease management. At presentation, radiolabeled pentetreotide scintigraphy was the only procedure able to detect the ectopic source of ACTH. After radiologic confirmation, the patient underwent removal of a bronchial carcinoid, with disease persistence. After surgery, pentetreotide scintigraphy showed pathologic uptake in the mediastinum not previously detected at surgery and only subsequently confirmed by radiologic studies. Despite a second thoracic exploration, hormonal, scintigraphic, and radiological evidence of residual disease persisted. Radioguided surgery was then performed using a hand-held gamma probe 48 h after iv administration of a tracer dose of radiolabeled [111In-DTPA-D-Phe1]-pentetreotide, which permitted detection and removal of multiple residual mediastinal lymph node metastases. Clinical and radiologic cure, with no evidence of tracer uptake at pentetreotide scintigraphy, was subsequently observed. The use of an intraoperative gamma counter appears a promising procedure in the management of metastatic ACTH-secreting bronchial carcinoids.

  3. Effect of MSH/ACTH peptides on fast axonal transport in intact and regenerating sciatic nerves

    SciTech Connect

    Crescitelli, L.A.

    1985-01-01

    Fast axonal transport was examined in intact rats treated with ACTH 4-10 or ACTH 4-9 (ORG 2766), hypophysectomized rats, adrenalectomized rats, and in ACTH 4-10 treated rats with crushed regenerating sciatic nerves by injecting /sup 3/H-leucine into the ventral horn region of the spinal cord. The distance traveled by the transported activity along the sciatic nerve and the rate of fast axonal transport were not significantly altered as a result of treatment with ACTH 4-10, ACTH 4-9 (ORG 2766), hypophysectomy, or adrenalectomy. Treatment with ACTH 4-9 (ORG 2766) at concentrations of 1 ..mu..g/Kg /day and 10 ..mu..g/Kg/day caused significant reductions (62% and 64% respectively) in the crest height of the fast axonal transport curve as compared to 0.9% saline treated control animals. No significant differences were found in comparing the distance, rate, slope, or crest height of ACTH 4-10 treated animals with crushed regenerating (7 or 14d) sciatic nerves to control animals. In the group of animals in days, the amount of radiolabeled activity was significantly increased in the ACTH 4-10 treated animals as compared to control animals. The results indicate that during regeneration the peptide acts to prolong the initially high levels of synthetic activity which occur in regenerating axons.

  4. Uptake and release of adrenal ascorbic acid in the guinea pig after injection of ACTH

    SciTech Connect

    Kipp, D.E.; Rivers, J.M.

    1987-09-01

    The effect of a single injection of ACTH (3 IU/100 g body weight) on the distribution of ascorbic acid (AA) and radiolabeled AA in 20 tissues was studied in adult male guinea pigs consuming 500 mg AA/kg diet. Saline- or ACTH-injected animals were simultaneously injected with (1-/sup 14/C)AA, and killed at 0.5, 1, 2, 4 and 6 h after injection. There was no significant difference between treatments in the weight of any tissue over the 6-h experimental period. As anticipated, the concentration of AA in the adrenals of animals injected with ACTH was 33% of that of animals injected with saline at 4 h. Unexpectedly, the concentration of radiolabeled AA in the adrenals at 0.5 h after ACTH injection was 172% of that after saline injection. The concentration of radiolabeled AA in the adrenal of the saline-injected animals increased slowly over time to reach a level similar to that of ACTH-injected animals by 6 h. There was no effect of ACTH on the level of AA or uptake in any of the other tissues examined. These results demonstrate that a single dose of ACTH markedly influences the retention of AA in the adrenal gland without similarly altering retention of AA in other tissues. Furthermore, ACTH treatment causes both accelerated uptake and release of AA into the adrenals.

  5. ACTH acts via an anterior ventral third ventricular site to elicit grooming behavior.

    PubMed

    Dunn, A J; Hurd, R W

    1986-01-01

    Intracerebroventricular but not parenteral application of ACTH has been shown to elicit excessive grooming behavior in rats and mice. This behavior is elicited by administration of ACTH into the lateral, third, or fourth ventricles. Plugging of the cerebral aqueduct with cold cream fails to prevent grooming in response to lateral ventricle injection of ACTH. However, cold cream plugs in the third ventricle can prevent the subsequent induction of grooming behavior by lateral ventricle injection of ACTH, but only when the plugs are located in the anterior ventral third ventricle in the region of the organum vasculosum laminae terminalis (OVLT) and median eminence. These data suggest the anterior ventral third ventricle as the periventricular site of action of ACTH in eliciting excessive grooming, although it is possible that peptides taken up in this area are transported to other regions to elicit the behavioral response.

  6. Metabolic effects of chronic ACTH administration, interaction with response to stress.

    PubMed

    Armario, A; Campmany, L; Hidalgo, J

    1986-01-01

    The present experiment was undertaken to study the metabolic response to stress of single or chronic ACTH-treated male rats. It was found that chronic ACTH-treated rats showed a slight reduction in food intake and a decrease in body weight gain. This treatment increased basal serum triglyceride and insulin levels. In addition, some differences in response to stress was found in chronic ACTH-treated rats. Thus, these latter animals, unlike the other two groups, showed a decrease in circulating triglyceride and insulin levels in response to short-term stress. Moreover, 24 h after onset of stress a more marked fall in liver weight and glucose levels were found in chronic ACTH-treated rats. It suggests that chronic ACTH treatment might alter the metabolic response to prolonged acute stress what could result in lower resistance to severe stresses.

  7. How porphyrinogenic drugs modeling acute porphyria impair the hormonal status that regulates glucose metabolism. Their relevance in the onset of this disease.

    PubMed

    Matkovic, Laura B; D'Andrea, Florencia; Fornes, Daiana; San Martín de Viale, Leonor C; Mazzetti, Marta B

    2011-11-28

    This work deals with the study of how porphyrinogenic drugs modeling acute porphyrias interfere with the status of carbohydrate-regulating hormones in relation to key glucose enzymes and to porphyria, considering that glucose modulates the development of the disease. Female Wistar rats were treated with 2-allyl-2-isopropylacetamide (AIA) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) using different doses of AIA (100, 250 and 500mg/kg body weight) and a single dose of DDC (50mg DDC/kg body weight). Rats were sacrificed 16h after AIA/DDC administration. In the group treated with the highest dose of AIA (group H), hepatic 5-aminolevulinic acid synthase (ALA-S) increased more than 300%, phosphoenolpyruvate carboxykinase (PEPCK) and glycogen phosphorylase (GP) activities were 43% and 46% lower than the controls, respectively, plasmatic insulin levels exceeded normal values by 617%, and plasmatic glucocorticoids (GC) decreased 20%. GC results are related to a decrease in corticosterone (CORT) adrenal production (33%) and a significant reduction in its metabolization by UDP-glucuronosyltransferase (UGT) (62%). Adrenocorticotropic hormone (ACTH) stimulated adrenal production 3-fold and drugs did not alter this process. Thus, porphyria-inducing drugs AIA and DDC dramatically altered the status of hormones that regulate carbohydrate metabolism increasing insulin levels and reducing GC production, metabolization and plasmatic levels. In this acute porphyria model, gluconeogenic and glycogenolytic blockages caused by PEPCK and GP depressed activities, respectively, would be mainly a consequence of the negative regulatory action of insulin on these enzymes. GC could also contribute to PEPCK blockage both because they were depressed by the treatment and because they are positive effectors on PEPCK. These disturbances in carbohydrates and their regulation, through ALA-S de-repression, would enhance the porphyria state promoted by the drugs on heme synthesis and destruction

  8. Influences of ACTH 4-10 on event-related potentials reflecting attention in man.

    PubMed

    Born, J; Fehm-Wolfsdorf, G; Voigt, K H; Fehm, H L

    1987-01-01

    The present paper is concerned with effects of the 4-10 sequence of the endogenous ACTH on electrophysiological measures of attention in humans. It was attempted to replicate previous findings of an impaired selective attention following administration of an analog of ACTH 4-9. The effect of this analog had been found to dominate in the beginning of the blocks of an attention task, but to fade away with time on task. In the present study, fourteen male students were tested in a dichotic listening paradigm, 40 min after intranasal application of either 0.4 mg ACTH 4-10, or placebo. Averaged auditory evoked potentials (AEPs) to attended and inattended tone pips, EEG power spectra, heart rate and blood pressure, and behavioral performance were measured during task performance. ACTH 4-10 appeared to slightly impair selective attention as indicated by AEP responses. In particular, the positive shift of the AEP waveforms to inattended stimuli was reduced at the beginning of each block of tone pips under ACTH 4-10. The pattern of actions resembled the effects observed after administration of the more potent synthetic analog of ACTH 4-9 in the previous experiment. Effects of ACTH 4-10 on the AEPs to inattended stimuli, however, differed from influences of the synthetic analog in that they did not affect a rather wide latency range but concentrated on the latency range of the P200 component.

  9. Effect of ACTH on plasma corticosterone and cortisol in eagles and condors.

    PubMed

    Zenoble, R D; Kemppainen, R J; Young, D W; Carpenter, J W

    1985-12-01

    The effect of ACTH on plasma corticosterone and cortisol was determined in 12 eagles (Haliaeetus leucocephalus) and in 6 Andean condors (Vultur gryphus). In all raptors, the concentration of plasma corticosterone was substantially greater than that of cortisol. After ACTH administration, the eagles had a marked increase (P less than 0.001) in plasma corticosterone concentrations, but not in plasma cortisol. Administration of saline solution did not induce increased plasma corticosterone concentrations in the eagles. The condors had a smaller increase (P less than 0.002) in plasma corticosterone concentrations after ACTH administration, as compared with that of the eagles. However, administration of saline solution in 2 condors resulted in an increase in corticosterone similar to the increase after ACTH administration. In the condor, a stress-related release of endogenous ACTH may have an effect similar to that induced by exogenously administered ACTH. Plasma cortisol concentrations did not increase significantly after administration of ACTH or saline solution in either raptor species.

  10. Effect of ACTH on plasma corticosterone and cortisol in eagles and condors

    USGS Publications Warehouse

    Zenoble, R.D.; Kemppainen, R.J.; Young, D.W.; Carpenter, J.W.

    1985-01-01

    The effect of ACTH on plasma corticosterone and cortisol was determined in 12 eagles (Haliaeetus leucocephalus) and in 6 Andean condors (Vultur gryphus). In all raptors, the concentration of plasma corticosterone was substantially greater than that of cortisol. After ACTH administration, the eagles had a marked increase (P less than 0.001) in plasma corticosterone concentrations, but not in plasma cortisol. Administration of saline solution did not induce increased plasma corticosterone concentrations in the eagles. The condors had a smaller increase (P less than 0.002) in plasma corticosterone concentrations after ACTH administration, as compared with that of the eagles. However, administration of saline solution in 2 condors resulted in an increase in corticosterone similar to the increase after ACTH administration. In the condor, a stress-related release of endogenous ACTH may have an effect similar to that induced by exogenously administered ACTH. Plasma cortisol concentrations did not increase significantly after administration of ACTH or saline solution in either raptor species.

  11. Acromegaly and Cushing's syndrome due to ectopic production of GHRH and ACTH by a thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6.

    PubMed

    Jansson, J O; Svensson, J; Bengtsson, B A; Frohman, L A; Ahlman, H; Wängberg, B; Nilsson, O; Nilsson, M

    1998-02-01

    A 50-year-old male presented with diabetes mellitus and Cushing's syndrome associated with a large mediastinal mass. The levels of serum cortisol were high (1500-1800 nmol/l) without diurnal variation. Plasma ACTH levels (200-250 ng/l) and urinary excretion of cortisol were also increased. The levels of these hormones did not change in response to stimulation with corticotrophin releasing hormone (CRH) or suppression with high doses of dexamethasone. The patient had an elevated baseline GH level (7.3 mU/l), and the levels of immunoreactive GH-releasing hormone (GHRH) in eight plasma samples were markedly increased (600-1500 ng/l). Circulating levels of IGF-1, chromogranin A and neuropeptide Y (NPY) were also increased. Computer-assisted tomography and octreotide scintigraphy revealed a large mediastinal tumour and metastases in the left supraclavicular fossa. During treatment with octreotide, the baseline GH level was decreased (to 4.4 mU/l), while the GH pulse height was unchanged. Surgical removal of most of the tumour tissue resulted in a further decrease in the baseline serum GH level to a value (1.6 mU/l) about 20% of that before treatment, while the pulse height and mean GH were affected to a lesser extent. Postoperatively, circulating levels of cortisol and IGF-1 decreased, and the patient exhibited clinical improvement. Histological examination showed a neuroendocrine tumour with characteristics consistent with a foregut carcinoid of thymic origin. Immunoreactive GHRH, ACTH and NPY, but not immunoreactive GH, were detected in 80-90% of the tumour cells and the three peptides appeared to be co-localized. In primary culture, cells from this tumour displayed calcium influx in response to GHRH or GH releasing peptide-6 (GHRP-6), while there were not such responses by cells from another carcinoid not producing GHRH, ACTH or NPY. These results demonstrate a rare case of ectopic production of GHRH, ACTH and NPY, and indicate that the tumour cells were responsive

  12. Growth hormone replacement therapy in Costello syndrome.

    PubMed

    Triantafyllou, Panagiota; Christoforidis, Athanasios; Vargiami, Euthymia; Zafeiriou, Dimitrios I

    2014-12-01

    Costello syndrome (CS) is considered an overgrowth disorder given the macrosomia that is present at birth .However, shortly after birth the weight drops dramatically and the patients are usually referred for failure to thrive. Subsequently, affected patients develop the distinctive coarse facial appearance and are at risk for cardiac anomalies and solid tumor malignancies. Various endocrine disorders, although not very often, have been reported in patients with CS, including growth hormone deficiency, hypoglycemia, ACTH deficiency, cryptorchidism and hypothyroidism. We report a case of Costello syndrome with hypothyroidism, cryptorchidism and growth hormone deficiency and we evaluate the long-term safety and efficacy of growth hormone replacement therapy. The index patient is a paradigm of successful and safe treatment with growth hormone for almost 7 years. Since patients with CS are at increased risk for cardiac myopathy and tumor development they deserve close monitoring during treatment.

  13. Hormonal secretion and quality of life in Nelson syndrome and Cushing disease after long acting repeatable octreotide: a short series and update.

    PubMed

    Arregger, Alejandro L; Cardoso, Estela M L; Sandoval, Olga B; Monardes Tumilasci, Elida G; Sanchez, Rocío; Contreras, Liliana N

    2014-01-01

    Clinical management of persistent adrenocorticotropin hormone (ACTH) excess in Nelson syndrome (NS) and Cushing disease (CD) remains a challenge. Somatostatin and its analogs as octreotide decrease ACTH secretion through somatostatin receptors of pituitary cells. To our knowledge, there are no reports on the effect of long-acting repeatable octreotide (oct-lar) on hormonal secretion and quality of life in patients with NS and CD who failed conventional therapy. Herein, we describe the effects of treatment with oct-lar (20 mg/month intramurally) in 1 woman with NS and 2 women with persistent CD. Oct-lar therapy reduced ACTH secretion and improved the quality of life in NS patient. By contrast, in CD patients, it failed to control ACTH and cortisol secretion, and the quality of life remained unchanged.

  14. OmniGen-AF alters rectal temperature (RT) and leukocyte profiles in dairy cows exposed to heat stress (HS) following acute activation of the stress axis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Differences in the response of OmniGen-AF (OG) supplemented dairy cows to a corticotropin releasing hormone (CRH) and vasopressin (VP) or an adrenocorticotropic hormone (ACTH) challenge when housed at different temperature-humidity indices (THI) were studied. Holstein cows (n=12; 162±1 days in milk)...

  15. Possible relationship between elevated plasma ACTH and tall stature in familial glucocorticoid deficiency.

    PubMed

    Imamine, Hiroki; Mizuno, Haruo; Sugiyama, Yukari; Ohro, Yoichiro; Sugiura, Tokio; Togari, Hajime

    2005-02-01

    Familial glucocorticoid deficiency (FGD) is characterized clinically by severe glucocorticoid deficiency associated with failure of adrenal responsiveness to ACTH but not with mineralcorticoid deficiency. Excessive growth was described previously in some patients with FGD, many of whom were shown to have mutations in the ACTH receptor gene. The mechanisms responsible for their excessive growth are unknown. We analyzed the ACTH receptor gene in three patients with FGD and discussed the causes of excessive growth in FGD. No mutations were detected in the coding and promoter regions of the ACTH receptor gene of one female patient who had tall stature (+ 2.41S.D.) and advanced bone age (10 years 9 months) when she was 4 years 9 months old. Her plasma ACTH level had been elevated until then (124-2,684 pg/ml). Moreover, plasma estradiol was elevated for her age (21.3 pg/ml), and it decreased in response to the dexamethasone suppression test (from 25.4 to 6.9 pg/ml). Elevated plasma estradiol was apparently related to the increase in plasma ACTH and played a major role in excessive growth in this patient. On the other hand, the genetic analysis showed that the other two patients who were siblings were homozygous for the R137W mutation. Clinically, they responded well to hydrocortisone replacement therapy with almost normal plasma ACTH levels. Although all patients with the R137W mutation reported previously were tall, our patients were of normal height. We speculate that the major causes of excessive growth in FGD are not only from ACTH receptor mutation, but also from the action of elevated plasma ACTH.

  16. Ectopic ACTH syndrome due to pheochromocytoma: case report and review of the literature.

    PubMed Central

    Forman, B. H.; Marban, E.; Kayne, R. D.; Passarelli, N. M.; Bobrow, S. N.; Livolsi, V. A.; Merino, M.; Minor, M.; Farber, L. R.

    1979-01-01

    A 51-year-old female was diagnosed preoperatively to have a pheochromocytoma producing ACTH. This diagnosis was based upon her paroxysmal hypertension, hyperpigmentation, and hypokalemia. Elevated levels of serum and urine corticosteroids, plasma ACTH, urinary VMA, and catecholamines fell after a right adrenal pheochromocytoma was removed. Subsequently this tumor was found to have a high content of ACTH. Review of the literature indicates a mortality rate of 57% for this syndrome. Proper preoperative recognition and management can result in total cure. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:222080

  17. Hypothalamic hypopituitarism in a patient with a basal encephalocoele--treatment with luteinizing hormone-releasing hormone.

    PubMed Central

    Morris, D. V.; Mason, W. P.; Wilson-Holt, N.; Adams, J.; Keene, M.; Tanner, J.; Jacobs, H. S.

    1984-01-01

    A 20-year-old patient presented with primary amenorrhoea and growth hormone deficiency caused by a basal encephalocoele. She was found to have developed diabetes insipidus in the 8 years following diagnosis. Gonadotrophin release in response to bolus injection of luteinizing hormone-releasing hormone (LHRH) was normal, as was thyrotrophin and adrenocorticotrophin (ACTH) secretion. Pulsatile administration of LHRH by the subcutaneous route resulted in normal ovulation and subsequent menstruation. The investigation and management of patients with basal encephalocoeles are discussed in the light of these findings. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:6384984

  18. Hormones, nicotine, and cocaine: clinical studies.

    PubMed

    Mello, Nancy K

    2010-06-01

    Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (2 min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine's sustained positive effects (<20 min), ratings of "high" and "rush" began to decrease within one or two puffs of a high-nicotine cigarette while nicotine levels were increasing. Peak nicotine levels increased progressively after each of three successive cigarettes smoked at 60 min intervals, but the magnitude of the subjective effects ratings and peak ACTH and cortisol levels diminished. Only DHEA increased consistently after successive cigarettes. The possible influence of neuroactive hormones on nicotine dependence and cocaine abuse and the implications for treatment of these addictive disorders are discussed.

  19. Hormones, Nicotine and Cocaine: Clinical Studies

    PubMed Central

    Mello, Nancy K.

    2009-01-01

    Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels, and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (two min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine’s sustained positive effects (< 20 min), ratings of “High” and “Rush” began to decrease within one or two puffs of a high nicotine cigarette while nicotine levels were increasing. Peak nicotine levels increased progressively after each of three successive cigarettes smoked at 60 min intervals, but the magnitude of the subjective effects ratings and peak ACTH and cortisol levels diminished. Only DHEA increased consistently after successive cigarettes. The possible influence of neuroactive hormones on nicotine dependence and cocaine abuse, and implications for treatment of these addictive disorders is discussed. PMID:19835877

  20. CHANNEL CATFISH, ICTALURUS PUNCTATUS, LEUKOCYTES SECRETE IMMUNOREACTIVE ADRENAL CORTICOTROPIN HORMONE (ACTH). (R823881)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  1. [Acute pancreatitis after bilateral laparoscopic adrenalectomy in patients with ectopic ACTH syndrome].

    PubMed

    Cougard, P; Peix, J L; Peschaud, F; Goudet, P

    2001-05-01

    Two cases of acute necrotizing pancreatitis after bilateral laparoscopic adrenalectomy were observed in patients with an ectopic ACTH syndrome. Two reasons may be suspected: the difficulty of dissection in such patients and the specific morbidity in relation to hypercorticism.

  2. ACTH and vasopressin responses to insulin-induced hypoglycemia in intact and neurohypophysectomized conscious dogs.

    PubMed

    Raff, H; Papanek, P E; Cowley, A W

    1991-01-01

    Factors from the neurohypophysis are important in the control of anterior pituitary function. This study evaluated the hypothesis that the neurophypophysis is an integral component of the adrenocorticotropin (ACTH) response to certain stimuli. Furthermore, we investigated the possibility that the importance of the neurohypophysis during corticotropic stimuli can be classified by the magnitude of the systemic vasopressin response induced. The ACTH response to insulin-induced hypoglycemia (INS), nitroprusside hypotension (NP), or ovine corticotropin-releasing factor (CRF) infusion (20 ng/kg/min) was measured in dogs before (intact) and greater than 2 weeks after selective transbuccal neurohypophysectomy (NHX). INS (0.2 U/kg) resulted in a significant decrease in plasma glucose from 93 +/- 1 to 33 +/- 2 mg/dl at 30 min and a significant increase in plasma ACTH from 53 +/- 10 to 306 +/- 33 pg/ml in intact dogs whereas the vasopressin (AVP) response was small (2.8 +/- 0.3 to 5.5 +/- 0.7 pg/ml). NHX had no effect on the blood glucose or ACTH response to INS. NP resulted in large increases in ACTH from 54 +/- 8 to 351 +/- 89 pg/ml and in AVP from 2.7 +/- 0.2 to 272 +/- 98 pg/ml. In contrast to INS, NHX significantly attenuated the ACTH and AVP responses to NP. The ACTH response to CRF was not attenuated by NHX, indicating normal pituitary corticotropic function. In summary, NHX attenuated the ACTH response to hypotension (large peripheral AVP response) but not to INS or CRF (small peripheral AVP response).(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Decrease of N-acetylaspartate after ACTH therapy in patients with infantile spasms.

    PubMed

    Maeda, H; Furune, S; Nomura, K; Kitou, O; Ando, Y; Negoro, T; Watanabe, K

    1997-10-01

    Apparent brain atrophy has been frequently observed at CT and MRI after ACTH therapy in patients with infantile spasms. There are several hypotheses to explain ACTH-induced brain shrinkage: 1) a catabolic effect of ACTH on brain tissue, 2) a mineralocorticoid effect resulting in a loss of water and 3) an increase in cerebrospinal fluid (CSF) pressure compressing the brain. An average of 0.21 +/- 0.03 mg/kg of ACTH was administered to nine patients over a period of 14 to 17 days. Water content and concentrations of N-acetylaspartate (NAA), creatine and phosphocreatine (Cr + PCr), and choline (Cho) were measured before, immediately after, and several months after the ACTH therapy by using in-vivo 1H magnetic resonance spectroscopy (MRS). Only NAA concentration exhibited a significant change during the study (6.6 +/- 1.5 mmol/kg, 5.4 +/- 1.1, and 7.0 +/- 1.5, p = 0.017). There was no significant change in Cr + PCr, in Cho, or in water content. These data suggest catabolic effects of ACTH on brain tissue, such as cell loss, decrease in NAA synthesis in mitochondria, and leakage of NAA from cell membrane.

  4. Corticotropin-releasing hormone links pituitary adrenocorticotropin gene expression and release during adrenal insufficiency.

    PubMed

    Muglia, L J; Jacobson, L; Luedke, C; Vogt, S K; Schaefer, M L; Dikkes, P; Fukuda, S; Sakai, Y; Suda, T; Majzoub, J A

    2000-05-01

    Corticotropin-releasing hormone (CRH)-deficient (KO) mice provide a unique system to define the role of CRH in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Despite several manifestations of chronic glucocorticoid insufficiency, basal pituitary proopiomelanocortin (POMC) mRNA, adrenocorticotrophic hormone (ACTH) peptide content within the pituitary, and plasma ACTH concentrations are not elevated in CRH KO mice. The normal POMC mRNA content in KO mice is dependent upon residual glucocorticoid secretion, as it increases in both KO and WT mice after adrenalectomy; this increase is reversed by glucocorticoid, but not aldosterone, replacement. However, the normal plasma levels of ACTH in CRH KO mice are not dependent upon residual glucocorticoid secretion, because, after adrenalectomy, these levels do not undergo the normal increase seen in KO mice despite the increase in POMC mRNA content. Administration of CRH restores ACTH secretion to its expected high level in adrenalectomized CRH KO mice. Thus, in adrenal insufficiency, loss of glucocorticoid feedback by itself can increase POMC gene expression in the pituitary; but CRH action is essential for this to result in increased secretion of ACTH. This may explain why, after withdrawal of chronic glucocorticoid treatment, reactivation of CRH secretion is a necessary prerequisite for recovery from suppression of the HPA axis.

  5. Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones.

    PubMed

    Senovilla, Laura; Núñez, Lucía; de Campos, José María; de Luis, Daniel A; Romero, Enrique; García-Sancho, Javier; Villalobos, Carlos

    2015-01-01

    Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs.

  6. [Hormone content of the blood plasma of rats after a flight on the Kosmos-1129 biosatellite].

    PubMed

    Tigranian, R A; Kalita, N F; Macho, L; Kvetnanský, R

    1985-01-01

    The concentration of ACTH, insulin, glucagon, glucose, epinephrine, norepinephrine, thyrotrophic hormone, thyroxine, and triiodothyronine was measured in plasma of the rats flown for 18.5 days on Cosmos-1129. As a result of the flight, the concentration of insulin, thyrotrophic hormone, and triiodothyronine increased and that of thyroxine decreased. It is suggested that the above changes have been induced by an acute stress associated with biosatellite reentry and touchdown.

  7. The significance of ACTH for the process of formation of complex heparin compounds in the blood during immobilization stress

    NASA Technical Reports Server (NTRS)

    Kudryashov, B. A.; Shapiro, F. B.; Lomovskaya, F. B.; Lyapina, L. A.

    1979-01-01

    Adrenocorticotropin (ACTH) was administered to rats at different times following adrenalectomy. Adrenocorticotropin caused a significant increase in the formation of heparin complexes even in the absence of stress factor. When ACTH secretion is blocked, immobilization stress is not accompanied by an increase in the process of complex formation. The effect of ACTH on the formation of heparin complexes was mediated through its stimulation of the adrenal cortex.

  8. The corticotropin-releasing hormone test in normal short children: comparison of plasma adrenocorticotropin and cortisol responses to human corticotropin-releasing hormone and insulin-induced hypoglycemia.

    PubMed

    Goji, K

    1989-03-01

    The human corticotropin-releasing hormone (hCRH) tests were performed in twelve normal short children, and the responses of plasma ACTH and cortisol to iv administration of 1 micrograms/kg hCRH were compared with those to insulin-induced hypoglycemia. After administration of hCRH, the mean plasma ACTH level rose from a basal value of 3.3 +/- 0.4 pmol/l (mean +/- SEM) to a peak value of 9.2 +/- 0.8 pmol/l at 30 min, and the mean plasma cortisol level rose from a basal value of 231 +/- 25 nmol/l to a peak value of 546 +/- 30 nmol/l at 30 min. The ACTH response after insulin-induced hypoglycemia was greater than that after hCRH administration; the mean peak level (P less than 0.01), the percent maximum increment (P less than 0.01), and the area under the ACTH response curve (P less than 0.01) were all significantly greater after insulin-induced hypoglycemia than those after hCRH administration. Although the mean peak cortisol level after insulin-induced hypoglycemia was about 1.3-fold higher than that after hCRH administration (P less than 0.01), neither the percent maximum increment in plasma cortisol nor the area under the cortisol response curve after insulin-induced hypoglycemia was significantly different from that after hCRH administration. Consequently, the acute increases in plasma ACTH after the administration of 1 microgram/kg hCRH stimulated the adrenal gland to almost the same cortisol response as that obtained with a much greater increase in plasma ACTH after insulin-induced hypoglycemia. These results suggest that a plasma ACTH peak of 9-11 pmol/l produces near maximum acute stimulation of adrenal steroidogenesis.

  9. Hormonal changes in antiorthostatic rats

    NASA Technical Reports Server (NTRS)

    Popovic, V.; Popovic, P.; Honeycutt, C.

    1982-01-01

    Hypokinesia, especially hypokinesia with negative tilt ('antiorthostatic hypokinesia'), mimics some of the effects of weightlessness. It is shown that cardiac output is increased during early exposure of rats to antiorthostatic hypokinesia. The increase of the stroke volume and of the cardiac output observed in the antiorthostatic hypokinetic rats is probably the consequence of a blood volume shift toward the chest brought forth by head-down positioning of the animals. It is also possible that struggling of the animals to escape from the harness and an increased metabolism contribute to the elevation of cardiac output. In order to study this hypothesis 'stress hormones' were measured in the antiorthostatic rats. Plasma levels of ACTH, corticosterone and prolactin were measured in the arterial blood (0.3 ml) sampled before, during and after hypokinesia from chronic aortic cannulas of the rats.

  10. Characterization of a novel ACTH inducible cytochrome P-450 from rat adrenal microsomes

    SciTech Connect

    Otto, S.A.; Marcus, C.M.; Jefcoate, C.R. )

    1990-02-26

    In rat adrenal cortex 7,12 dimethylbenz(a)anthracene (DMBA) causes massive necrosis that is dependent of ACTH. This is related to an ACTH inducible adrenal microsomal cytochrome P-450 that catalyzes hydrocarbon metabolism. Rat adrenal microsomes, catalyze the formation of DMBA 3,4 diol a precursor of the bay region reactive electrophile DMBA 3,4 diol 1,2 oxide. Both DMBA metabolism and a 57Kd protein have disappeared from microsomes 30 days after hypophysectomy, but are restored by 14 days treatment with ACTH. Dexamethasone which fully suppresses ACTH only partially suppresses this activity. The 57 Kd protein was partially purified to a single major band in one step from solubilized microsomes by h.p.l.c. chromatography using detergent elution from a novel column that mimics phospholipid membranes. This preparation exhibits a specific content of 2 nm P-450/mg protein and a turnover number of 1,500pm DMBA/nm P-450/minutes. A polyclonal antisera raised against this preparation provides a single western blot corresponding to the 57Kd ACTH sensitive protein. This antibody did not blot microsomal P-450 c21, nor did selected antibodies from known families react with this adrenal P-450 protein, suggesting substantial sequence differences from known P-450's.

  11. Luteinizing hormone (LH)-releasing hormone agonist reduces serum adrenal androgen levels in prostate cancer patients: implications for the effect of LH on the adrenal glands.

    PubMed

    Nishii, Masahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Oyama, Tetsunari; Suzuki, Kazuhiro

    2012-01-01

    Recently, adrenal androgens have been targeted as key hormones for the development of castration-resistant prostate cancer therapeutics. Although circulating adrenal androgens originate mainly from the adrenal glands, the testes also supply about 10%. Although widely used in androgen deprivation medical castration therapy, the effect of luteinizing hormone-releasing hormone (LH-RH) agonist on adrenal androgens has not been fully studied. In this study, changes in testicular and adrenal androgen levels were measured and compared to adrenocorticotropic hormone levels. To assess the possible role of LH in the adrenal glands, immunohistochemical studies of the LH receptor in normal adrenal glands were performed. Forty-seven patients with localized or locally progressive prostate cancer were treated with LH-RH agonist with radiotherapy. Six months after initiation of treatment, testosterone, dihydrotestosterone, and estradiol levels were decreased by 90%-95%, and dehydroepiandrosterone-sulfate, dehydroepiandrosterone, and androstenedione levels were significantly decreased by 26%-40%. The suppressive effect of LH-RH agonist at 12 months was maintained. Adrenocorticotropic hormone levels showed an increasing trend at 6 months and a significant increase at 12 months. LH receptors were positively stained in the cortex cells of the reticular layer of the adrenal glands. The long-term LH-RH agonist treatment reduced adrenal-originated adrenal androgens. LH receptors in the adrenal cortex cells of the reticular layer might account for the underlying mechanism of reduced adrenal androgens.

  12. Somatostatin system: molecular mechanisms regulating anterior pituitary hormones.

    PubMed

    Eigler, Tamar; Ben-Shlomo, Anat

    2014-08-01

    The somatostatin (SRIF) system, which includes the SRIF ligand and receptors, regulates anterior pituitary gland function, mainly inhibiting hormone secretion and to some extent pituitary tumor cell growth. SRIF-14 via its cognate G-protein-coupled receptors (subtypes 1-5) activates multiple cellular signaling pathways including adenylate cyclase/cAMP, MAPK, ion channel-dependent pathways, and others. In addition, recent data have suggested SRIF-independent constitutive SRIF receptor activity responsible for GH and ACTH inhibition in vitro. This review summarizes current knowledge on ligand-dependent and independent SRIF receptor molecular and functional effects on hormone-secreting cells in the anterior pituitary gland.

  13. Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta

    SciTech Connect

    Robinson, B.G.; Emanuel, R.L.; Frim, D.M.; Majzoub, J.A. )

    1988-07-01

    Primary cultures of purified human cytotrophoblasts have been used to examine the expression of the corticotropin-releasing hormone (CRH) gene in placenta. The authors report here that glucocorticoids stimulate placental CRH synthesis and secretion in primary cultures of human placenta. This stimulation is in contrast to the glucocorticoid suppression of CRH expression in hypothalamus. The positive regulation of CRH by glucocorticoids suggests that the rise in CRH preceding parturition could result from the previously described rise in fetal glucocorticoids. Furthermore, this increase in placental CRH could stimulate, via adrenocorticotropic hormone, a further rise in fetal glucocorticoids, completing a positive feedback loop that would be terminated by delivery.

  14. Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta.

    PubMed Central

    Robinson, B G; Emanuel, R L; Frim, D M; Majzoub, J A

    1988-01-01

    Primary cultures of purified human cytotrophoblasts have been used to examine the expression of the corticotropin-releasing hormone (CRH) gene in placenta. We report here that glucocorticoids stimulate placental CRH synthesis and secretion in primary cultures of human placenta. This stimulation is in contrast to the glucocorticoid suppression of CRH expression in hypothalamus. The positive regulation of CRH by glucocorticoids suggests that the rise in CRH preceding parturition could result from the previously described rise in fetal glucocorticoids. Furthermore, this increase in placental CRH could stimulate, via adrenocorticotropic hormone, a further rise in fetal glucocorticoids, completing a positive feedback loop that would be terminated by delivery. Images PMID:2839838

  15. Rapid Glucocorticoid Feedback Inhibition of ACTH Secretion Involves Ligand-Dependent Membrane Association of Glucocorticoid Receptors

    PubMed Central

    Deng, Qiong; Riquelme, Denise; Trinh, Loc; Low, Malcolm J.; Tomić, Melanija; Stojilkovic, Stanko

    2015-01-01

    The hypothesis that rapid glucocorticoid inhibition of pituitary ACTH secretion mediates a feedforward/feedback mechanism responsible for the hourly glucocorticoid pulsatility was tested in cultured pituitary cells. Perifusion with 30 pM CRH caused sustained the elevation of ACTH secretion. Superimposed corticosterone pulses inhibited CRH-stimulated ACTH release, depending on prior glucocorticoid clearance. When CRH perifusion started after 2 hours of glucocorticoid-free medium, corticosterone levels in the stress range (1 μM) caused a delayed (25 min) and prolonged inhibition of CRH-stimulated ACTH secretion, up to 60 minutes after corticosterone withdrawal. In contrast, after 6 hours of glucocorticoid-free medium, basal corticosterone levels inhibited CRH-stimulated ACTH within 5 minutes, after rapid recovery 5 minutes after corticosterone withdrawal. The latter effect was insensitive to actinomycin D but was prevented by the glucocorticoid receptor antagonist, RU486, suggesting nongenomic effects of the classical glucocorticoid receptor. In hypothalamic-derived 4B cells, 10 nM corticosterone increased immunoreactive glucocorticoid receptor content in membrane fractions, with association and clearance rates paralleling the effects on ACTH secretion from corticotrophs. Corticosterone did not affect CRH-stimulated calcium influx, but in AtT-20 cells, it had biphasic effects on CRH-stimulated Src phosphorylation, with early inhibition and late stimulation, suggesting a role for Src phosphorylation on the rapid glucocorticoid feedback. The data suggest that the nongenomic/membrane effects of classical GR mediate rapid and reversible glucocorticoid feedback inhibition at the pituitary corticotrophs downstream of calcium influx. The sensitivity and kinetics of these effects is consistent with the hypothesis that pituitary glucocorticoid feedback is part of the mechanism for adrenocortical ultradian pulse generation. PMID:26121342

  16. [1H-NMR studies of the ACTH-like immunoregulatory peptides].

    PubMed

    Khristoforov, V S; Kutyshenko, V P; Abramov, V M; Zav'ialov, V P

    1997-01-01

    A comparative study of the conformational and dynamics properties of the ACTH-like linear peptides, sequences of which correspond to amino acid residues 11-20 of the heavy chain of human immunoglobulin G1 Eu, residues 78-85 of human pro-interleukin-1 alpha and site 10-18 of human ACTH, was performed in aqueous solution and dimethylsulfoxide by 1H-NMR spectroscopy at 400 MHz. The peptides were shown to possess an unordered unfolded flexible conformation in aqueous solution. The revealed structural and dynamic features of the peptides are discussed together with biological activity of this class of compounds.

  17. Loss of sensitivity to ACTH of adrenocortical cells isolated from maturing domestic fowl.

    PubMed

    Carsia, R V; Scanes, C G; Malamed, S

    1985-07-01

    Maturation of domestic fowl corticosteroidogenesis was evaluated using purified adrenocortical cells. Basal corticosterone production decreased steadily from 2 days to 26 weeks after hatching. However, maximally stimulated corticosterone production was not changed. In contrast, the half-maximal steroidogenic concentrations (ED50 values or effective doses for 50% maximal effect) of ACTH analogs increased approximately 40 times by 26 weeks, but the ED50 values of 8-bromo-cyclic AMP and pregnenolone were not changed. This suggests that adrenocortical cell sensitivity to ACTH decreases with maturation of the domestic fowl.

  18. Chronic Stress and Performance

    DTIC Science & Technology

    2011-09-01

    body by increasing adrenaline and adrenocorticotropic hormone (ACTH) that produces cortisol. Cells in the amygdala have shown to increase after...exist, they ignore the relationship between the intensity, duration , type of nociceptive model used, and type of stressor. Currently, few attempts...with different time increments of physical stress duration . Humans in particular react differently to stress depending on the type of stressor

  19. ATRAZINE DOES NOT INDUCE GASTROINTESTINAL DISCOMFORT (PICA) IN RATS AT DOSES THAT INCREASE HPA-AXIS ACTIVATION AND CAUSE CONDITIONED TASTE AVERSION.

    EPA Science Inventory

    Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH) and serum corticosterone (CORT), with a NOEL equal to 5mg/kg. The mechanism for these effects ...

  20. Hormone Therapy

    MedlinePlus

    ... estrogen , a hormone that helps control the menstrual cycle . Changing estrogen levels can bring on symptoms such ... two hormones—estrogen and progesterone —control your menstrual cycle. These hormones are made by the ovaries . Estrogen ...

  1. Corticotropin (ACTH)-reactive immunoglobulins in adolescents in relation to antisocial behavior and stress-induced cortisol response. The TRAILS study.

    PubMed

    Schaefer, Johanna M; Fetissov, Serguei O; Legrand, Romain; Claeyssens, Sophie; Hoekstra, Pieter J; Verhulst, Frank C; Van Oort, Floor V A

    2013-12-01

    Elevated levels of corticotropin (ACTH)-reactive immunoglobulins (ACTH IgG) were found in males with conduct disorder, suggesting their involvement in the biology of antisocial behavior. We first aimed to confirm these findings in a large general population sample of adolescents. Secondly, we studied the association between ACTH IgG levels and hypothalamic-pituitary-adrenal (HPA) axis response to stress. Free and total ACTH IgG levels were measured in sera of 1230 adolescents (15-18 years). HPA axis activity was determined by measuring salivary cortisol before, during, and after a social stress test. Antisocial behavior was assessed using the Antisocial Behavior Questionnaire. ACTH peptide and IgG affinity kinetics for ACTH were assayed in a subsample of 90 adolescents selected for high or low ACTH IgG levels. In boys, higher total ACTH IgG levels were associated with higher antisocial behavior scores (β=1.05, p=0.04), especially at high levels of free ACTH IgG. In girls, antisocial behavior was associated with low free ACTH IgG levels (β=-0.20, p=0.04). Stress-induced cortisol release was associated with free ACTH IgG in boys (βareaunderthecurve=-0.67, p<0.01), and with total ACTH IgG in girls (βrecovery=0.84, p=0.05). The affinity kinetics assay showed that ACTH IgG association rates were lower in both boys and girls with high ACTH IgG levels. These data show that ACTH IgG levels are related to antisocial behavior and HPA axis response to stress in adolescents. The mechanisms behind these associations, including different ACTH binding properties of IgG in subjects with antisocial behavior, deserve further attention.

  2. Does aerobic exercise affect the hypothalamic-pituitary-adrenal hormonal response in patients with fibromyalgia syndrome?

    PubMed Central

    Genc, Aysun; Tur, Birkan Sonel; Aytur, Yesim Kurtais; Oztuna, Derya; Erdogan, Murat Faik

    2015-01-01

    [Purpose] The hypothalamic-pituitary-adrenal (HPA) axis in the etiopathogenesis of fibromyalgia is not clear. This study aimed to analyze the effects of a 6-week aerobic exercise program on the HPA axis in patients with fibromyalgia and to investigate the effects of this program on the disease symptoms, patients’ fitness, disability, and quality of life. [Subjects and Methods] Fifty fibromyalgia patients were randomized to Group 1 (stretching and flexibility exercises at home for 6 weeks) and Group 2 (aerobic exercise three times a week and the same at-home exercises as Group 1 for 6 weeks). Serum levels of cortisol, adrenocorticotropic hormone, insulin-like growth factor-1, and growth hormone were analyzed at baseline and at the end of, and 1 hr after an exercise stress test. [Results] Group 2 showed better improvement in morning stiffness duration and pain. Growth hormone levels significantly increased after intervention and cortisol levels significantly decreased at time-time interaction in both groups. No significant differences in adrenocorticotropic hormone and insulin-like growth factor-1 were found. [Conclusion] The results of this study seem to support the hypothesis that there is a dysregulation of the HPA axis in patients with FM, and that a six-week exercise program can influence symptoms and affect the HPA axis hormones. PMID:26311959

  3. GH-releasing peptide (GHRP-6)-induced ACTH release in patients with addison's disease: effect of glucocorticoid withdrawal.

    PubMed

    Martins, M R A; Pinto, A C A R; Brunner, E; Silva, M R D; Lengyel, A M J

    2003-02-01

    GH releasing peptide (GHRP-6) is a synthetic hexapeptide with potent GH releasing activity both in man and in animals. This peptide is also able to stimulate ACTH and cortisol (F) release. It has been suggested that the ACTH responsiveness to GHRP-6 is modulated by circulating glucocorticoid levels. To further clarify this hypothesis, we studied the effect of GHRP-6 (1 ug/kg, iv) on ACTH and F release in patients with Addison's disease (no.=6) during replacement therapy and after 72 h of glucocorticoid withdrawal. Seven controls were also submitted to a single GHRP-6 test. In control subjects, ACTH values (pmol/l; mean +/- SE) increased from 2.9 +/- 0.8 to 4.7 +/- 1.4 (peak). AUC (pmol.min/l) values were 170.3 +/- 48.8. F (nmol/l) values increased from 257.0 +/- 42.9 to 367.0 +/- 50.8. In patients with Addison's disease there was an increase in ACTH levels from 38.1 +/- 17.1 to 174.9 +/- 79.4 after GHRP-6 administration. AUC values were 5490.4 +/- 2269.1. After 72 h withdrawal of glucocorticoid, there was an increase in basal ACTH values (191.2 +/- 97.3), and a trend toward an increase in ACTH levels after GHRP-6 (p=0.053). Patients with Addison's disease on therapy showed a significantly higher ACTH response to GHRP-6 when compared to controls. Our results show that in patients with Addison's disease on replacement there is an increased ACTH release after GHRP-6 administration, compared to controls. After 72 h glucocorticoid withdrawal, this enhanced responsiveness is not maintained. Our data suggest that circulating glucocorticoids modulate GHRP-6-induced ACTH release and that multiple mechanisms may be involved in this process.

  4. Reevaluation of lipolytic activity of growth hormone in rabbit adipocytes.

    PubMed

    Barenton, B; Batifol, V; Combarnous, Y; Dulor, J P; Durand, P; Vezinhet, A

    1984-07-18

    The lipolytic activities of porcine pituitary fractions and purified growth hormone (GH) from human (h), porcine (p), ovine (o) and rabbit (Rb) origin as well as ovine placental lactogen (oPL), were compared to that of ACTH on rabbit adipocytes. All the GH preparations and oPL were equivalent in inhibiting the binding of labelled oGH to liver plasma membranes from pregnant rabbits. ACTH, and to a lesser extent porcine pituitary fractions and hGH, stimulated free fatty acid production by isolated adipocytes. The sensitivity of the adipocytes to these factors was increased when adenosine deaminase was added to the incubation medium. But, RbGH, pGH, oGH and oPL had no effect. We conclude that GH is not directly involved in the control of lipolysis in rabbit adipocytes and that the effect of hGH is rather due to a contamination of this preparation by other pituitary factors.

  5. Acute effects of ACTH on dissociated adrenocortical cells: quantitative changes in mitochondria and lipid droplets.

    PubMed

    Zoller, L C; Malamed, S

    1975-08-01

    To study the role of certain organelles in steroidogenesis, dissociated rat adrenocortical cells were incubated for two hours with ACTH at a concentration that induces a high level of steroid production. Sections of ACTH treated and untreated cells were photographed in the electron microscope, and morphometric analysis was undertaken to assess possible ACTH-induced changes in total cell volume, volume density and numerical denisty of lipid droplets and mitochondria. There was no change in total cell volume. Lipid droplet volume density and numerical density decreased. Mitochondrial volume density did not change, but numerical density increased. The decrease in lipid droplet volume density indicates a rapid depletion of cholesterol for steroid production. This depletion is almost entirely due to the disappearance of lipid droplets, rather than to an overall diminution in their size, as shown by the decrease in lipid droplet numerical density. The mitochondrial data suggest that the adrenocortical cell has an adedquate mitochondrial apparatus to respond to acute ACTH stimulation with increased steroid output without an increase inmitochondrial volume.

  6. Prior Exercise Alters Responses to Hemorrhage

    DTIC Science & Technology

    2010-07-01

    for the swine in our laboratory (4, 17). Plasma renin activ- ity (PRA), aldosterone, cortisol, and adrenocorticotropic hormone (ACTH) were measured...could aid in their care. Exercise acutely reduces blood volume, increases plasma lactate concentrations, and alters the hormonal /immunologic milieu...concentration was measured enzymatically with a commercial kit (Sigma Chemical Co, St Louis, Mo). Hormone concentrations were measured with tech- niques validated

  7. Investigating Genomic Mechanisms of Treatment Resistance in Castration Resistant Prostate Cancer

    DTIC Science & Technology

    2014-05-01

    2010) Editorial Comment on Adrenocorticotropic hormone (ACTH) regulates androgen synthesis in men receiving androgen deprivation therapy for...to collect hormone , pK, and CTC/biopsy data, which will allow for an analysis of the mechanisms of resistance to abiraterone. Statement of Work... hormonal , immunologic, and chemotherapeutic strategies to treat these patients. B. Positions and Honors Positions and Employment 2003-2006 Medical

  8. Melanocortin receptor agonist ACTH 1-39 protects rat forebrain neurons from apoptotic, excitotoxic and inflammation-related damage.

    PubMed

    Lisak, Robert P; Nedelkoska, Liljana; Bealmear, Beverly; Benjamins, Joyce A

    2015-11-01

    Patients with relapsing-remitting multiple sclerosis (RRMS) are commonly treated with high doses of intravenous corticosteroids (CS). ACTH 1-39, a member of the melanocortin family, stimulates production of CS by the adrenals, but melanocortin receptors are also found in the central nervous system (CNS) and on immune cells. ACTH is produced within the CNS and may have direct protective effects on glia and neurons independent of CS. We previously reported that ACTH 1-39 protected oligodendroglia (OL) and their progenitors (OPC) from a panel of excitotoxic and inflammation-related agents. Neurons are the most vulnerable cells in the CNS. They are terminally differentiated, and sensitive to inflammatory and excitotoxic insults. For potential therapeutic protection of gray matter, it is important to investigate the direct effects of ACTH on neurons. Cultures highly enriched in neurons were isolated from 2-3 day old rat brain. After 4-7 days in culture, the neurons were treated for 24h with selected toxic agents with or without ACTH 1-39. ACTH 1-39 protected neurons from death induced by staurosporine, glutamate, NMDA, AMPA, kainate, quinolinic acid, reactive oxygen species and, to a modest extent, from rapidly released NO, but did not protect against kynurenic acid or slowly released nitric oxide. Our results show that ACTH 1-39 protects neurons in vitro from several apoptotic, excitotoxic and inflammation-related insults.

  9. Hormonal regulation of colour change in eyes of a cryptic fish.

    PubMed

    Sköld, Helen Nilsson; Yngsell, Daniel; Mubashishir, Muhmd; Wallin, Margareta

    2015-01-16

    Colour change of the skin in lower vertebrates such as fish has been a subject of great scientific and public interest. However, colour change also takes place in eyes of fish and while an increasing amount of data indicates its importance in behaviour, very little is known about its regulation. Here, we report that both eye and skin coloration change in response to white to black background adaptation in live sand goby Pomatoschistus minutes, a bentic marine fish. Through in vitro experiments, we show that noradrenaline and melanocyte concentrating hormone (MCH) treatments cause aggregation of pigment organelles in the eye chromatophores. Daylight had no aggregating effect. Combining forskolin to elevate intracellular cyclic adenosine monophosphate (cAMP) with MCH resulted in complete pigment dispersal and darkening of the eyes, whereas combining prolactin, adrenocorticotrophic hormone (ACTH) or melanocyte stimulating hormone (α-MSH) with MCH resulted in more yellow and red eyes. ACTH and MSH also induced dispersal in the melanophores, resulting in overall darker eyes. By comparing analysis of eyes, skin and peritoneum, we conclude that the regulation pattern is similar between these different tissues in this species which is relevant for the cryptic life strategy of this species. With the exception of ACTH which resulted in most prominent melanophore pigment dispersal in the eyes, all other treatments provided similar results between tissue types. To our knowledge, this is the first study that has directly analysed hormonal regulation of physiological colour change in eyes of fish.

  10. Hormonal responses to opioid receptor blockade: during rest and exercise in cold and hot environments.

    PubMed

    Armstrong, David W; Hatfield, Bradley D

    2006-05-01

    Opioid receptors appear to modulate a variety of physiological and metabolic homeostatic responses to stressors such as exercise and thermally extreme environments. To more accurately determine the role of the naloxone (NAL) sensitive opioid receptor system during rest and exercise, subjects were subjected to concomitant environmental thermal stress. Fifteen untrained men rested or performed low intensity (60% VO2peak) or high intensity (80% VO2peak) exercise on a cycle ergometer for 60 min in an environmental chamber during cold (0 degrees C) hot (35 degrees C) air exposure while receiving an infusion of normal saline (SAL) or NAL (0.1 mg kg(-1)). Plasma adrenocorticotropin hormone (ACTH), immunoreactive beta-endorphin (IBE), cortisol and growth hormone were measured at baseline and every 15 min while in the chamber. Time to exhaustion was significantly reduced during high intensity exercise in the heat (P<0.0001). NAL significantly (P=0.0004) reduced the time to exhaustion (38.3+/-2.1 min) during high intensity exercise in the heat compared to SAL (49.4+/-2.1 min). ACTH and IBE increased during hot conditions and cold attenuated this response. Plasma concentrations of IBE, ACTH, and growth hormone increased significantly with NAL during high intensity exercise in the heat compared to SAL. Cold attenuated the response of ACTH, IBE and cortisol to NAL. NAL administration exaggerates plasma hormone concentration during high intensity exercise in the heat, but not cold. These results support a regulatory effect of the opioid receptor system on physiological responses during exercise in thermally stressful environments. Future research should be directed to more clearly defining the effect of environmental temperature on the mechanism of hypothalamic-pituitary-adrenal hormonal release during exercise and hot environmental temperatures.

  11. Severe hypokalemia, metabolic alkalosis and hypertension in a 54 year old male with ectopic ACTH syndrome: a case report.

    PubMed

    Martínez-Valles, Miguel Angel; Palafox-Cazarez, Asael; Paredes-Avina, Jose Antonio

    2009-07-31

    Ectopic ACTH syndrome is a rare cause of Cushing's syndrome accounting for about 15% of all cases. Small cell lung cancer and bronchial carcinoids account for about half of the cases. Malignant neoplasm has rapid and more aggressive metabolic effects. We report a 54-year-old male patient with phenotypic features of Cushing's syndrome with severe hypokalemia, metabolic alkalosis, hypertension and altered mental status as manifestations of an ACTH-secreting small cell carcinoma from the lung. Ectopic ACTH syndrome should be highly considered in patients with hypertension and severe hypokalemic metabolic alkalosis, especially when a lung mass is discovered.

  12. The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin.

    PubMed

    Larzul, C; Terenina, E; Foury, A; Billon, Y; Louveau, I; Merlot, E; Mormede, P

    2015-12-01

    In the search for biological basis of robustness, this study aimed (i) at the determination of the heritability of the cortisol response to ACTH in juvenile pigs, using restricted maximum likelihood methodology applied to a multiple trait animal model, and (ii) at the study of the relationships between basal and stimulated cortisol levels with corticosteroid-binding globulin (CBG), IGF-I and haptoglobin, all important players in glucose metabolism and production traits. At 6 weeks of age, 298 intact male and female piglets from 30 litters (30 dams and 30 boars) were injected with 250 µg ACTH(1-24) (Synacthen). Blood was taken before ACTH injection to measure basal levels of cortisol, glucose, CBG, IGF-I and haptoglobin, and 60 min later to measure stimulated cortisol levels and glucose. Cortisol increased 2.8-fold after ACTH injection, with a high correlation between basal and stimulated levels (phenotypic correlation, r p=0.539; genetic correlation, r g=0.938). Post-ACTH cortisol levels were highly heritable (h 2=0.684) and could therefore be used for genetic selection of animals with a more reactive hypothalamic-pituitary-adrenocortical axis. CBG binding capacity correlated with cortisol levels measured in basal conditions in males only. No correlation was found between CBG binding capacity and post-ACTH cortisol levels. Basal IGF-I concentration was positively correlated with BW at birth and weaning, and showed a high correlation with CBG binding capacity with a strong sexual dimorphism, the correlation being much higher in males than in females. Basal haptoglobin concentrations were negatively correlated with CBG binding capacity and IGF-I concentrations. Complex relationships were also found between circulating glucose levels and these different variables that have been shown to be related to glucose resistance in humans. These data are therefore valuable for the genetic selection of animals to explore the consequences on production and robustness traits, but

  13. Increased plasma ACTH in rats exposed to the elevated plus-maze is independent of the pineal gland.

    PubMed

    Appenrodt, E; Kröning, G; Schwarzberg, H

    1999-11-01

    The involvement of the pineal gland in activation of the hypothalamic-pituitary-adrenocortical (HPA) axis evoked by a stressful stimulus (exposure to the elevated plus-maze) was investigated. Plasma ACTH levels were measured in pinealectomized and pineal-intact rats (sham-operated and non-operated) immediately after a 5 min placement into a plus-maze. A statistically significant elevation in plasma ACTH was measured within all groups; however, no statistical differences between pinealectomized and pineal-intact rats were observed. Similarly, comparison of the plasma ACTH basal values obtained from animals only kept in their home cages did not reveal any statistical differences between pinealectomized and pineal-intact rats. From these results it can be concluded that the pineal gland is not involved in anxiety-related behavior and ACTH response.

  14. GHRP-6 is able to stimulate cortisol and ACTH release in patients with Cushing's disease: comparison with DDAVP.

    PubMed

    Oliveira, J H A; Vieira, J G H; Abucham, J; Lengyel, A M J

    2003-03-01

    It has been shown that hexarelin stimulates ACTH and cortisol secretion in patients with Cushing's disease. The ACTH release induced by this peptide is 7-fold greater than that obtained by hCRH. The mechanism of action of hexarelin on the hypothalamic-pituitary-adrenal axis has not been fully elucidated. Although controversial, there is evidence that it might be mediated by arginine vasopressin (AVP). The aim of this study was to evaluate the ACTH and cortisol releasing effects of GHRP-6 in patients with Cushing's disease and to compare them with those obtained with DDAVP administration. We studied 10 patients with Cushing's disease (8 female, 2 male; age: 36.7 +/- 4.2 yr), 9 with microadenomas, who were submitted to both GHRP-6 (2 microg/kg iv) and DDAVP (10 micro g i.v.) in bolus administration on 2 separate occasions. ACTH was measured by immunochemiluminometric assay and cortisol by radioimmunoassay. The sensitivities of the assays are 0.2 pmol/l for ACTH, and 11 nmol/l for cortisol. GHRP-6 was able to increase significantly both ACTH (pmol/l, mean +/- SE; basal: 15.5 +/- 1.7 vs peak: 45.1 +/- 9.3) and cortisol values (nmol/l, basal: 583.0 +/- 90.8 vs peak: 1013.4 +/- 194.6). ACTH AUC (pmol/l min(-1)) and cortisol AUC (nmol/l min(-1)) values were 1235.4 and 20577.2, respectively. After DDAVP administration there was a significant increase in ACTH (basal: 13.0 +/- 1.4 vs peak: 50.5 +/- 16.2) and cortisol levels (basal: 572.5 +/- 112.7 vs peak: 860.5 +/- 102.8. AUC values for ACTH and cortisol were 1627.6 +/- 639.8 and 18364.7 +/- 5661.4, respectively. ACTH and cortisol responses to GHRP-6 and DDAVP did not differ significantly (peak: 45.1 +/- 9.3 vs 50.5 +/- 16.2; AUC: 1235.4 +/- 424.8 vs 1627.6 +/- 639.8). There was a significant positive correlation between peak cortisol values after GHRP-6 and DDAVP administration (r = 0.87, p = 0.001). Our results show that GHRP-6 is able to stimulate ACTH and cortisol release in patients with Cushing's disease. These

  15. Severe hyponatremia caused by hypothalamic adrenal insufficiency.

    PubMed

    Shibata, T; Oeda, T; Saito, Y

    1999-05-01

    A 60-year-old woman was admitted with severe hyponatremia. Basal values of adrenocorticotropic hormone (ACTH), thyroid hormone and cortisol were normal on admission. Impairment of water diuresis was observed by water loading test. Initially, we diagnosed her condition as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). By provocation test, we finally confirmed that the hyponatremia was caused by hypothalamic adrenal insufficiency. The basal values of ACTH and cortisol might not be sufficient to exclude the possibility of adrenal insufficiency. Therefore, it is necessary to evaluate adrenal function by provocation test or to re-evaluate it after recovery from hyponatremia.

  16. Human and mouse TPIT gene mutations cause early onset pituitary ACTH deficiency

    PubMed Central

    Pulichino, Anne-Marie; Vallette-Kasic, Sophie; Couture, Catherine; Gauthier, Yves; Brue, Thierry; David, Michel; Malpuech, Georges; Deal, Cheri; Van Vliet, Guy; De Vroede, Monique; Riepe, Felix G.; Partsch, Carl-Joachim; Sippell, Wolfgang G.; Berberoglu, Merih; Atasay, Begüm; Drouin, Jacques

    2003-01-01

    Tpit is a highly cell-restricted transcription factor that is required for expression of the pro-opiomelanocortin (POMC) gene and for terminal differentiation of the pituitary corticotroph lineage. Its exclusive expression in pituitary POMC-expressing cells has suggested that its mutation may cause isolated deficiency of pituitary adrenocorticotropin (ACTH). We now show that Tpit-deficient mice constitute a model of isolated ACTH deficiency (IAD) that is very similar to human IAD patients carrying TPIT gene mutations. Through genetic analysis of a panel of IAD patients, we show that TPIT gene mutations are associated at high frequency with early onset IAD, but not with juvenile forms of this deficiency. We identified seven different TPIT mutations, including nonsense, missense, point deletion, and a genomic deletion. This work defines congenital early onset IAD as a relatively homogeneous clinical entity caused by recessive transmission of loss-of-function mutations in the TPIT gene. PMID:12651888

  17. Studies on the possible central effects in man of a neuropeptide (ACTH 4-9 analogue).

    PubMed

    Nicholson, A N; Stone, B M; Jones, S J

    1984-01-01

    The central effects of a neuropeptide, ACTH 4-9 analogue (Organon 2766), were studied in man using digit symbol substitution (DSS), symbol copying, digit span, electroencephalography and auditory evoked potentials, critical flicker fusion (CFF) and pupillary response to light. Performance was measured overnight, and each of 6 subjects ingested 300 mg caffeine, 40 mg ACTH 4-9 analogue and matching placebo. With placebo there was a marked deterioration in performance overnight. The number of substitutions on DSS and the numbers of symbols copied fell, and the threshold for CFF and number of errors on the vigilance task increased. These effects were not seen after ingestion of caffeine (300 mg), though caffeine may have led to some deterioration in the ability to remember digits. The neuropeptide did not attenuate the decrements in performance overnight.

  18. Human and mouse TPIT gene mutations cause early onset pituitary ACTH deficiency.

    PubMed

    Pulichino, Anne-Marie; Vallette-Kasic, Sophie; Couture, Catherine; Gauthier, Yves; Brue, Thierry; David, Michel; Malpuech, Georges; Deal, Cheri; Van Vliet, Guy; De Vroede, Monique; Riepe, Felix G; Partsch, Carl-Joachim; Sippell, Wolfgang G; Berberoglu, Merih; Atasay, Begüm; Drouin, Jacques

    2003-03-15

    Tpit is a highly cell-restricted transcription factor that is required for expression of the pro-opiomelanocortin (POMC) gene and for terminal differentiation of the pituitary corticotroph lineage. Its exclusive expression in pituitary POMC-expressing cells has suggested that its mutation may cause isolated deficiency of pituitary adrenocorticotropin (ACTH). We now show that Tpit-deficient mice constitute a model of isolated ACTH deficiency (IAD) that is very similar to human IAD patients carrying TPIT gene mutations. Through genetic analysis of a panel of IAD patients, we show that TPIT gene mutations are associated at high frequency with early onset IAD, but not with juvenile forms of this deficiency. We identified seven different TPIT mutations, including nonsense, missense, point deletion, and a genomic deletion. This work defines congenital early onset IAD as a relatively homogeneous clinical entity caused by recessive transmission of loss-of-function mutations in the TPIT gene.

  19. Validating the Novel Method of Measuring Cortisol Levels in Cetacean Skin by use of an ACTH Challenge in Bottlenose Dolphins

    DTIC Science & Technology

    2014-09-30

    Levels in Cetacean Skin by use of an ACTH Challenge in Bottlenose Dolphins 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Novel Method of Measuring Cortisol Levels in Cetacean Skin by use of an ACTH Challenge in Bottlenose Dolphins Thea Bechshoft Aarhus University...method (Bechshoft et al. Submitted) using skin samples collected from bottlenose dolphins (Tursiops truncatus). The dolphins will be sampled as part

  20. A case of severe ectopic ACTH syndrome from an occult primary – diagnostic and management dilemmas

    PubMed Central

    Griffin, Katherine; Amer, Saima

    2015-01-01

    Summary Resection of primary tumour is the management of choice in patients with ectopic ACTH syndrome. However, tumours may remain unidentified or occult in spite of extensive efforts at trying to locate them. This can, therefore, pose a major management issue as uncontrolled hypercortisolaemia can lead to life-threatening infections. We present the case of a 66-year-old gentleman with ectopic ACTH syndrome from an occult primary tumour with multiple significant complications from hypercortisolaemia. Ectopic nature of his ACTH-dependent Cushing's syndrome was confirmed by non-suppression with high-dose dexamethasone suppression test and bilateral inferior petrosal sinus sampling. The primary ectopic source remained unidentified in spite of extensive anatomical and functional imaging studies, including CT scans and Dotatate-PET scan. Medical adrenolytic treatment at maximum tolerated doses failed to control his hypercortisolaemia, which led to recurrent intra-abdominal and pelvic abscesses, requiring multiple surgical interventions. Laparoscopic bilateral adrenalectomy was considered but decided against given concerns of technical difficulties due to recurrent intra-abdominal infections and his moribund state. Eventually, alcohol ablation of adrenal glands by retrograde adrenal vein approach was attempted, which resulted in biochemical remission of Cushing's syndrome. Our case emphasizes the importance of aggressive management of hypercortisolaemia in order to reduce the associated morbidity and mortality and also demonstrates that techniques like percutaneous adrenal ablation using a retrograde venous approach may be extremely helpful in patients who are otherwise unable to undergo bilateral adrenalectomy. Learning points Evaluation and management of patients with ectopic ACTH syndrome from an unidentified primary tumour can be very challenging.Persisting hypercortisolaemia in this setting can lead to debilitating and even life-threatening complications and hence

  1. Neonatal isolated ACTH deficiency (IAD): a potentially life-threatening but treatable cause of neonatal cholestasis

    PubMed Central

    Alsaleem, Mahdi; Saadeh, Lina; Misra, Amrit; Madani, Shailender

    2016-01-01

    Isolated ACTH deficiency (IAD) is a rare cause of neonatal cholestasis and hypoglycaemia. This diagnosis has a 20% mortality potential if unrecognised. We describe a case of an infant presenting with cholestatic jaundice and hypoglycaemia. The patient had laboratory findings suggestive of IAD, which was later confirmed with molecular genetic testing. One of the mutations this patient had is a new finding. The patient was started on glucocorticoid replacement therapy after which his bilirubin and glucose levels normalised. PMID:27535729

  2. Is Prolactin Measurement of Value during Inferior Petrosal Sinus Sampling in Patients with ACTH-dependent Cushing’s Syndrome?

    PubMed Central

    Sharma, S. T.; Nieman, L. K.

    2014-01-01

    Inferior petrosal sinus sampling (IPSS) is considered the gold standard test to distinguish between Cushing’s disease (CD) and ectopic ACTH syndrome (EAS). Anomalous venous drainage, abnormal venous anatomy and lack of expertise can lead to false-negative IPSS results and thereby misclassification of patients with ACTH-dependent Cushing’s syndrome. Prolactin measurement during IPSS can improve diagnostic accuracy and decrease false negative results. A baseline prolactin inferior petrosal sinus to peripheral (IPS/P) ratio (ipsilateral to the dominant post-CRH ACTH IPS/P ratio) of 1.8 or more suggests successful catheterization during IPSS. Prolactin-normalized ACTH IPS/P ratios can then be used to differentiate between a pituitary and ectopic source of ACTH. Values ≤ 0.7 are suggestive of EAS and those ≥ 1.3 are indicative of CD but the implication of values between 0.7 and 1.3 remains unclear and needs further investigation. Larger prospective studies are also needed for further evaluation of the role of contralateral prolactin IPS/P ratios, post-CRH prolactin values and prolactin-adjusted ACTH inter-sinus ratios for tumor localization in CD. PMID:23887034

  3. Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions

    PubMed Central

    Lefebvre, Hervé; Thomas, Michaël; Duparc, Céline; Bertherat, Jérôme; Louiset, Estelle

    2016-01-01

    In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects that tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells that express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions. PMID:27489549

  4. Ectopic ACTH Production Leading to Diagnosis of Underlying Medullary Thyroid Carcinoma

    PubMed Central

    Matheny, Leslee N.; Wilson, Jessica R.; Baum, Howard B. A.

    2016-01-01

    Medullary thyroid carcinoma (MTC) has been described as a source of ectopic ACTH secretion in patients with Cushing’s syndrome. This is an infrequent association, occurring in less than 1% of MTC cases. Among these, it is even more unusual for an initial diagnosis of hypercortisolism to lead to the discovery of underlying MTC. Here we present a case of a patient with weakness, diarrhea, and hypokalemia who was found first to have Cushing’s syndrome and later diagnosed with metastatic MTC. The patient was treated initially with oral agents to control his hypercortisolism, then with an etomidate infusion after experiencing intestinal perforation. He also received vandetanib therapy targeting his underlying malignancy, as this has been shown to reverse clinical signs of Cushing’s syndrome in patients with MTC and subsequent ectopic ACTH secretion. Bilateral adrenalectomy was ultimately required. Medullary thyroid carcinoma should be considered in patients presenting with Cushing’s syndrome due to ectopic ACTH secretion, and a multimodality treatment approach is often required. PMID:27141514

  5. ACTH- and Cortisol-Associated Neutrophil Modulation in Coronary Artery Disease Patients Undergoing Stent Implantation

    PubMed Central

    Keresztes, Margit; Horváth, Tamás; Ocsovszki, Imre; Földesi, Imre; Serfőző, Gyöngyi; Boda, Krisztina; Ungi, Imre

    2013-01-01

    Background Psychosocial stress and activation of neutrophil granulocytes are increasingly recognized as major risk factors of coronary artery disease (CAD), but the possible relationship of these two factors in CAD patients is largely unexplored. Activation of neutrophils was reported to be associated with stenting; however, the issue of neutrophil state in connection with percutaneous coronary intervention (PCI) is incompletely understood from the aspect of stress and its hypothalamic-pituitary-adrenal axis (HPA) background. Thus, we aimed to study cortisol- and ACTH-associated changes in granulocyte activation in patients undergoing PCI. Methodology/Principal Findings Blood samples of 21 stable angina pectoris (SAP) and 20 acute coronary syndrome (ACS) patients were collected directly before (pre-PCI), after (post-PCI) and on the following day of PCI (1d-PCI). Granulocyte surface L-selectin, CD15 and (neutrophil-specific) lactoferrin were analysed by flow cytometry. Plasma cortisol, ACTH, and lactoferrin, IL-6 were also assayed. In both groups, pre- and post-PCI ratios of lactoferrin-bearing neutrophils were relatively high, these percentages decreased substantially next day; similarly, 1d-PCI plasma lactoferrin was about half of the post-PCI value (all p≤0.0001). Post-PCI ACTH was reduced markedly next day, especially in ACS group (SAP: p<0.01, ACS: p≤0.0001). In ACS, elevated pre-PCI cortisol decreased considerably a day after stenting (p<0.01); in pre-PCI samples, cortisol correlated with plasma lactoferrin (r∼0.5, p<0.05). In 1d-PCI samples of both groups, ACTH showed negative associations with the ratio of lactoferrin-bearing neutrophils (SAP: r = −0.601, p<0.005; ACS: r = −0.541, p<0.05) and with plasma lactoferrin (SAP: r = −0.435, p<0.05; ACS: r = −0.609, p<0.005). Conclusions/Significance Pre- and post-PCI states were associated with increased percentage of activated/degranulated neutrophils indicated by elevated lactoferrin

  6. Establishment and characterization of a human ovarian small cell carcinoma, hypercalcemic type, cell line (OS-1) secreting PTH, PthrP and ACTH--special reference to the susceptibility of anti-cancer drugs.

    PubMed

    Ohi, Satoshi; Niimi, Shigeki; Okada, Naoya; Yamada, Kyosuke; Tachibana, Toshiaki; Hashimoto, Hisashi; Nakajima, Masako; Yasuda, Mitsuru; Tanaka, Tadao; Sato, Kahei; Ishikawa, Hiroshi

    2004-12-01

    We successfully established a novel cell line (OS-1) derived from human ovarian small cell carcinoma, hypercalcemic type secreted PTH, PTH-rP and ACTH. The OS-1 cell line was established from metastatic focus of uterus. A patient was 25-year-old Japanese woman. The first she received left ovariectomy on April 2002. The histopathological diagnosis was ovarian small cell carcinoma, pT2c, Nx, Mx. Then on June 2003, metastatic focus of uterus was ectomied. A part of the recurrent tumor of uterus was cut into small pieces with razor blades, and dissociated with 0.1% trypsin-0.02% EDTA/ PBS(-) solution at room temperature. The single cells and small cell clusters were seeded into 60mm dishes and cultured in growth medium (GM: DMEM/F12 supplemented with 20% fetal bovine serum and 0.1% non-essential amino acids solution) at 37 degrees C, 4.7% CO2 in humidified air. Medium was exchanged twice a week. The OS-1 cells grew as floating cultures in the dishes. Radioimmunoassay of the conditioned media was revealed that the cultures secreted large amount of PTH, PTHrP and ACTH simultaneously. Susceptibilities of anti-cancer drugs to the OS-1 cells were examined using oxygen electrode meter (Daikin), and the results suggested VLB and TXL were effective, and CDDP, CPT-11, VP-16, VCR, CPA, MMC and CBDCA were not effective. In our knowledge, it is the first report that the cell line secreting PTH, PTHrP and ACTH was successfully established from ovarian small cell carcinoma, hypercalcemic type. We expect that OS-1 cell line contribute to study on the mechanism of ectopic hormone secretion and susceptibility of anti cancer drugs to the small cell carcinoma.

  7. Effect of immobilization and concurrent exposure to a pulse-modulated microwave field on core body temperature, plasma ACTH and corticosteroid, and brain ornithine decarboxylase, Fos and Jun mRNA.

    PubMed

    Stagg, R B; Hawel, L H; Pastorian, K; Cain, C; Adey, W R; Byus, C V

    2001-04-01

    Exposure of humans and rodents to radiofrequency (RF) cell phone fields has been reported to alter a number of stress- related parameters. To study this potential relationship in more detail, tube-restrained immobilized Fischer 344 rats were exposed in the near field in a dose-dependent manner to pulse-modulated (11 packets/s) digital cell phone microwave fields at 1.6 GHz in accordance with the Iridium protocol. Core body temperatures, plasma levels of the stress-induced hormones adrenocorticotrophic hormone (ACTH) and corticosterone, and brain levels of ornithine decarboxylase (Odc), Fos and Jun mRNAs were measured as potential markers of stress responses mediated by RF radiation. We tested the effects of the loose-tube immobilization with and without prior conditioning throughout a 2-h period (required for near-field head exposure to RF fields), on core body temperature, plasma ACTH and corticosteroids. Core body temperature increased transiently (+/-0.3 degrees C) during the initial 30 min of loose-tube restraint in conditioned animals. When conditioned/tube-trained animals were followed as a function of time after immobilization, both the ACTH and corticosterone levels were increased by nearly 10-fold. For example, within 2-3 min, ACTH increased to 83.2 +/- 31.0 pg/dl, compared to 28.1 +/- 7.7 pg/dl for cage controls, reaching a maximum at 15-30 min (254.6 +/- 46.8 pg/dl) before returning to near resting levels by 120 min (31.2 +/- 10.2 pg/dl). However, when non-tube-trained animals were submitted to loose-tube immobilization, these animals demonstrated significantly higher (3-10-fold greater) hormone levels at 120 min than their tube-trained counterparts (313.5 +/- 54.8 compared to 31.2 +/- 10.2 pg/dl; corticosterone, 12.2 +/- 6.2 microg/dl compared to 37.1 +/- 6.4 microg/dl). Hormone levels in exposed animals were also compared to those in swim-stressed animals. Swimming stress also resulted in marked elevation in both ACTH and corticosterone levels, which

  8. Comparison of salivary and calculated free cortisol levels during low and standard dose of ACTH stimulation tests in healthy volunteers.

    PubMed

    Elbuken, Gulsah; Tanriverdi, Fatih; Karaca, Zuleyha; Kula, Mustafa; Gokahmetoglu, Selma; Unluhizarci, Kursad; Kelestimur, Fahrettin

    2015-03-01

    Salivary cortisol (SC) has been increasingly used as a surrogate biomarker of free cortisol (FC) for the assessment of hypothalamo-pituitary-adrenal (HPA) axis, but there are not enough data regarding its use during ACTH stimulation tests. Therefore, we aimed to determine the responses of SC, calculated free cortisol (cFC) and free cortisol index (FCI) to ACTH stimulation tests in healthy adults. Forty-four healthy volunteers (24 men and 20 women) were included in the study. Low-dose (1 µg) and standard-dose (250 µg) ACTH stimulation tests were performed on two consecutive days. Basal and stimulated total cortisol (TC) and cortisol-binding globulin (CBG) levels and SC levels were measured during both doses of ACTH stimulation tests. cFC (by Coolens' equation) and FCI levels were calculated from simultaneously measured TC and CBG levels. The minimum SC, cFC, FCI levels after low-dose ACTH stimulation test were 0.21, 0.33, 16.06 µg/dL, and after standard-dose ACTH were 0.85, 0.46, 26.11 µg/dL, respectively, in healthy individuals who all had TC responses higher than 20 µg/dL. Peak CBG levels after both doses of ACTH stimulation tests were found to be higher in women than in men. So, by its effect, peak cFC and FCI levels were found to be lower in female than in male group. Neither TC nor SC levels were affected by gender. cFC and FCI levels depend on CBG levels and they are affected by gender. Cut-off levels for SC, cFC, FCI levels after both low- and standard-dose ACTH stimulation are presented. Studies including patients with adrenal insufficiency would be helpful to see the diagnostic value of these suggested cut-off levels.

  9. The hormonal system of the unicellular Tetrahymena: a review with evolutionary aspects.

    PubMed

    Csaba, György

    2012-06-01

    The unicellular ciliate, Tetrahymena has receptors for hormones of the higher ranked animals, these hormones (e.g. insulin, triiodothyronine, ACTH, histamine, etc.) are also produced by it and it has signal pathways and second messengers for signal transmission. These components are chemically and functionally very similar to that of mammalian ones. The exogenously given hormones regulate different functions, as movement, phagocytosis, chemotaxis, cell growth, secretion, excretion and the cells' own hormone production. The receptors are extremely sensitive, certain hormones are sensed (and response is provoked) at 10-21 M concentration, which makes likely that the function could work by the effect of hormones produced by the Tetrahymena itself. The signal reception is selective, it can differentiate between closely related hormones. The review is listing the hormones produced by the Tetrahymena, the receptors which can receive signals and the signal pathways and second messengers as well, as the known effects of mammalian hormones to the life functions of Tetrahymena. The possible and justified role of hormonal system in the Tetrahymena as a single cell and inside the Tetrahymena population, as a community is discussed. The unicellular hormonal system and mammalian endocrine system are compared and evolutionary conclusions are drawn.

  10. How do the many etiologies of West syndrome lead to excitability and seizures? The corticotropin releasing hormone excess hypothesis

    PubMed Central

    Brunson, Kristen L.; Eghbal-Ahmadi, Mariam; Baram, Tallie Z.

    2011-01-01

    West syndrome (WS) is associated with diverse etiological factors. This fact has suggested that there must be a ‘final common pathway’ for these etiologies, which operates on the immature brain to result in WS only at the maturational state present during infancy. Any theory for the pathogenesis of WS has to account for the unique features of this disorder. For example, how can a single entity have so many etiologies? Why does WS arise only in infancy, even when a known insult had occurred prenatally, and why does it disappear? Why is WS associated with lasting cognitive dysfunction? And, importantly, why do these seizures – unlike most others – respond to treatment by a hormone, ACTH? The established hormonal role of ACTH in human physiology is to function in the neuroendocrine cascade of the responses to all stressful stimuli, including insults to the brain. As part of this function, ACTH is known to suppress the production of corticotropin releasing hormone (CRH), a peptide that is produced in response to diverse insults and stressors. The many etiologies of WS all lead to activation of the stress response, including increased production and secretion of the stress-neurohormone CRH. CRH has been shown, in infant animal models, to cause severe seizures and death of neurons in areas involved with learning and memory. These effects of CRH are restricted to the infancy period because the receptors for CRH, which mediate its action on neurons, are most abundant during this developmental period. ACTH administration is known to inhibit production and release of CRH via a negative feedback mechanism. Therefore, the efficacy of ACTH for WS may depend on its ability to decrease the levels of the seizure-promoting stress-neurohormone CRH. This CRH-excess theory for the pathophysiology of WS is consistent not only with the profile of ACTH effects, but also with the many different ‘causes’ of WS, with the abnormal ACTH levels in the cerebrospinal fluid of

  11. ACTH-induced caveolin-1 tyrosine phosphorylation is related to podosome assembly in Y1 adrenal cells

    SciTech Connect

    Colonna, Cecilia . E-mail: ccolonna@fmed.uba.ar; Podesta, Ernesto J.

    2005-04-01

    Y1 adrenocortical cells respond to ACTH with a characteristic rounding-up that facilitates cAMP signaling, critical for transport of cholesterol to the mitochondria and increase in steroid secretion. We here demonstrate that caveolin-1 participates in coupling activation of protein kinase A (PKA) to the control of cell shape. ACTH/8-Br-cAMP induced reorganization of caveolin-1-positive structures in correlation with the cellular rounding-up. Concomitant with this change, there was an increase in the phosphorylation of caveolin-1 (Tyr-14) localized at focal adhesions (FA) with reorganization of FA to rounded, ringlike structures. Colocalization with phalloidin showed that phosphocaveolin is present at the edge of actin filaments and that after ACTH stimulation F-actin dots at the cell periphery become surrounded by phosphocaveolin-1. These observations along with electron microscopy studies revealed these structures as podosomes. Podosome assembly was dependent on both PKA and tyrosine kinase activities because their formation was impaired after treatment with specific inhibitors [myristoylated PKI (mPKI) or PP2, respectively] previous to ACTH/8-Br-cAMP stimulation. These results show for the first time that ACTH induces caveolin-1 phosphorylation and podosome assembly in Y1 cells and support the view that the morphological and functional responses to PKA activation in steroidogenic cells are related to cytoskeleton dynamics.

  12. ACTH-induced caveolin-1 tyrosine phosphorylation is related to podosome assembly in Y1 adrenal cells.

    PubMed

    Colonna, Cecilia; Podestá, Ernesto J

    2005-04-01

    Y1 adrenocortical cells respond to ACTH with a characteristic rounding-up that facilitates cAMP signaling, critical for transport of cholesterol to the mitochondria and increase in steroid secretion. We here demonstrate that caveolin-1 participates in coupling activation of protein kinase A (PKA) to the control of cell shape. ACTH/8-Br-cAMP induced reorganization of caveolin-1-positive structures in correlation with the cellular rounding-up. Concomitant with this change, there was an increase in the phosphorylation of caveolin-1 (Tyr-14) localized at focal adhesions (FA) with reorganization of FA to rounded, ringlike structures. Colocalization with phalloidin showed that phosphocaveolin is present at the edge of actin filaments and that after ACTH stimulation F-actin dots at the cell periphery become surrounded by phosphocaveolin-1. These observations along with electron microscopy studies revealed these structures as podosomes. Podosome assembly was dependent on both PKA and tyrosine kinase activities because their formation was impaired after treatment with specific inhibitors [myristoylated PKI (mPKI) or PP2, respectively] previous to ACTH/8-Br-cAMP stimulation. These results show for the first time that ACTH induces caveolin-1 phosphorylation and podosome assembly in Y1 cells and support the view that the morphological and functional responses to PKA activation in steroidogenic cells are related to cytoskeleton dynamics.

  13. Effects of RXR Agonists on Cell Proliferation/Apoptosis and ACTH Secretion/Pomc Expression

    PubMed Central

    Saito-Hakoda, Akiko; Uruno, Akira; Yokoyama, Atsushi; Shimizu, Kyoko; Parvin, Rehana; Kudo, Masataka; Saito-Ito, Takako; Sato, Ikuko; Kogure, Naotaka; Suzuki, Dai; Shimada, Hiroki; Yoshikawa, Takeo; Fujiwara, Ikuma; Kagechika, Hiroyuki; Iwasaki, Yasumasa; Kure, Shigeo; Ito, Sadayoshi; Sugawara, Akira

    2015-01-01

    Various retinoid X receptor (RXR) agonists have recently been developed, and some of them have shown anti-tumor effects both in vivo and in vitro. However, there has been no report showing the effects of RXR agonists on Cushing’s disease, which is caused by excessive ACTH secretion in a corticotroph tumor of the pituitary gland. Therefore, we examined the effects of synthetic RXR pan-agonists HX630 and PA024 on the proliferation, apoptosis, ACTH secretion, and pro-opiomelanocortin (Pomc) gene expression of murine pituitary corticotroph tumor AtT20 cells. We demonstrated that both RXR agonists induced apoptosis dose-dependently in AtT20 cells, and inhibited their proliferation at their higher doses. Microarray analysis identified a significant gene network associated with caspase 3 induced by high dose HX630. On the other hand, HX630, but not PA024, inhibited Pomc transcription, Pomc mRNA expression, and ACTH secretion dose-dependently. Furthermore, we provide new evidence that HX630 negatively regulates the Pomc promoter activity at the transcriptional level due to the suppression of the transcription factor Nur77 and Nurr1 mRNA expression and the reduction of Nur77/Nurr1 heterodimer recruiting to the Pomc promoter region. We also demonstrated that the HX630-mediated suppression of the Pomc gene expression was exerted via RXRα. Furthermore, HX630 inhibited tumor growth and decreased Pomc mRNA expression in corticotroph tumor cells in female nude mice in vivo. Thus, these results indicate that RXR agonists, especially HX630, could be a new therapeutic candidate for Cushing’s disease. PMID:26714014

  14. The effect of ACTH upon faecal glucocorticoid excretion in the koala.

    PubMed

    Davies, Nicole; Gillett, Amber; McAlpine, Clive; Seabrook, Leonie; Baxter, Greg; Lunney, Daniel; Bradley, Adrian

    2013-10-01

    Environmental changes result in physiological responses of organisms, which can adversely affect population dynamics and reduce resistance to disease. These changes are expressed in chronic levels of stress. The measurement of glucocorticoid (GC) concentrations in faeces is a non-invasive method for monitoring stress in wildlife. The metabolism and excretion of steroids differ significantly between species and, as a consequence, non-invasive methods must be physiologically validated for each species. Koalas (Phascolarctos cinereus) are declining in numbers through much of their range. The role of chronic stress in koala populations has not been identified. Prior to the assessment of faecal GC concentrations in wild koala populations, the excretion timing and concentrations of GCs need to be determined. In this study, we assessed a method for identifying and measuring the concentrations of GC metabolites in faecal pellets of captive koalas following ACTH treatment. The results show that an elevation of plasma cortisol concentrations, using sustained release of ACTH, results in elevated concentrations of faecal cortisol/cortisol metabolites. Taking into account the excretion time lag, an increase in faecal cortisol metabolite concentrations corresponds to the release of GCs from the adrenal cortex as early as 36 h before faecal pellet collection. The calculations of steroid partitioning of plasma cortisol showed that the ACTH-stimulated values were significantly different from the control values for the concentrations of free, corticosteroid-binding globulin-bound and albumin-bound cortisol. This study validates the use of faecal cortisol analysis to assess the activity of the hypothalamo-pituitary-adrenocortical axis in freshly collected koala faecal pellets and indicates that the method should be suitable to assess the adrenocortical status of koalas in wild populations.

  15. ACTH-Independent Cushing’s Syndrome with Bilateral Micronodular Adrenal Hyperplasia and Ectopic Adrenocortical Adenoma

    PubMed Central

    Louiset, Estelle; Gobet, Françoise; Libé, Rossella; Horvath, Anelia; Renouf, Sylvie; Cariou, Juliette; Rothenbuhler, Anya; Bertherat, Jérôme; Clauser, Eric; Grise, Philippe; Stratakis, Constantine A.; Kuhn, Jean-Marc; Lefebvre, Hervé

    2010-01-01

    Context: Bilateral micronodular adrenal hyperplasia and ectopic adrenocortical adenoma are two rare causes of ACTH-independent Cushing’s syndrome. Objective: The aim of the study was to evaluate a 35-yr-old woman with ACTH-independent hypercortisolism associated with both micronodular adrenal hyperplasia and ectopic pararenal adrenocortical adenoma. Design and Setting: In vivo and in vitro studies were performed in a University Hospital Department and academic research laboratories. Intervention: Mutations of the PRKAR1A, PDE8B, and PDE11A genes were searched for in leukocytes and adrenocortical tissues. The ability of adrenal and adenoma tissues to synthesize cortisol was investigated by immunohistochemistry, quantitative PCR, and/or cell culture studies. Main Outcome Measure: Detection of 17α-hydroxylase and 21-hydroxylase immunoreactivities, quantification of CYP11B1 mRNA in adrenal and adenoma tissues, and measurement of cortisol levels in supernatants by radioimmunological assays were the main outcomes. Results: Histological examination of the adrenals revealed nonpigmented micronodular cortical hyperplasia associated with relative atrophy of internodular cortex. No genomic and/or somatic adrenal mutations of the PRKAR1A, PDE8B, and PDE11A genes were detected. 17α-Hydroxylase and 21-hydroxylase immunoreactivities as well as CYP11B1 mRNA were detected in adrenal and adenoma tissues. ACTH and dexamethasone activated cortisol secretion from adenoma cells. The stimulatory action of dexamethasone was mediated by a nongenomic effect involving the protein kinase A pathway. Conclusion: This case suggests that unknown molecular defects can favor both micronodular adrenal hyperplasia and ectopic adrenocortical adenoma associated with Cushing’s syndrome. PMID:19915020

  16. Analysis of the correlation between lipotoxicity and pituitary-thyroid axis hormone levels in men and male rats

    PubMed Central

    Yang, Jianmei; Zhou, Xiaoming; Zhang, Xu; Hu, Jianting; Gao, Ling; Song, Yongfeng; Yu, Chunxiao; Shao, Shanshan; Yuan, Zhongshang; Sun, Yan; Yan, Huili; Li, Guimei; Zhao, Jiajun

    2016-01-01

    Lipotoxicity seriously harms human health, but it is unclear whether lipotoxicity is detrimental to the pituitary. We investigated the correlation between serum triglyceride and pituitary axis hormone levels in epidemiological and animal studies. In the epidemiological study, serum thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were greater in male patients with isolated hypertriglyceridemia than in controls, whereas adrenocorticotropin (ACTH) levels were lower in the patients with hypertriglyceridemia. Pituitary hormone levels correlated with triglyceride levels, even after adjustment for potential confounders. In the animal study, male rats were fed a high-fat or control diet for 28 weeks. As the duration of high-fat feeding increased, the serum and pituitary triglyceride concentrations increased. At early times, the high-fat diet elevated serum TSH and triiodothyronine. At later times, much higher serum TSH levels coupled with reduced thyroxine were observed in the high-fat group. Serum levels of pituitary-gonadal and pituitary-adrenal axis hormones were not affected by the diet. The mRNA and protein expression of Tshβ were greater in the high-fat group than in the control group, whereas expression of Fshβ, Lhβ and Acth had no difference between the groups. Overall, serum triglyceride levels were associated with pituitary-thyroid axis hormone levels. PMID:27322428

  17. Inhibition of ACTH Release by Peptide Hormones: Molecular Mechanisms and Possible Role as Anti-Stress Factors

    DTIC Science & Technology

    1988-12-27

    applicable ) Office of Naval Research ONR N00014-88-K-0048 8c. ADDRESS (City, State, and ZIP Code) 10. SOURCE OF FUNDING NUMBERS 800 N. Quincv Street PROGRAM...With the photoactivated crosslinking agent HSAB , it was possible to covalently link [1251] CGP 23996 to the SRIF receptor in AtT-20 and GH3 cells as

  18. A novel mutation of the adrenocorticotropin receptor (ACTH-R) gene in a family with the syndrome of isolated glucocorticoid deficiency, but no ACTH-R abnormalities in two families with the triple A syndrome.

    PubMed

    Tsigos, C; Arai, K; Latronico, A C; DiGeorge, A M; Rapaport, R; Chrousos, G P

    1995-07-01

    Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by primary adrenocortical insufficiency, usually without mineralocorticoid deficiency. Occasionally, the disorder is associated with alacrima and achalasia of the esophagus (triple A syndrome), suggesting potential heterogeneity in its etiology. Mutations in the ACTH receptor gene have been reported in several families with IGD. We have amplified and directly sequenced the entire intronless ACTH receptor gene in 1 other family with IGD and 2 families with triple A syndrome. The proband with IGD was a homozygote for an A-->G substitution, changing tyrosine 254 to cysteine in the third extracellular loop of the receptor protein, probably interfering with ligand binding. Both of her parents were heterozygotes for this mutation, which was not detected in 100 normal alleles. No mutations were identified in the entire coding area of the ACTH receptor in the 2 families with triple A syndrome, supporting the idea of a developmental or postreceptor defect in this syndrome.

  19. High-Cholesterol Diet Disrupts the Levels of Hormones Derived from Anterior Pituitary Basophilic Cells.

    PubMed

    Yang, J; Zhang, X; Liu, Z; Yuan, Z; Song, Y; Shao, S; Zhou, X; Yan, H; Guan, Q; Gao, L; Zhang, H; Zhao, J

    2016-03-01

    Emerging evidence shows that elevated cholesterol levels are detrimental to health. However, it is unclear whether there is an association between cholesterol and the pituitary. We investigated the effects of a high-cholesterol diet on pituitary hormones using in vivo animal studies and an epidemiological study. In the animal experiments, rats were fed a high-cholesterol or control diet for 28 weeks. In rats fed the high-cholesterol diet, serum levels of thyroid-stimulating hormone (TSH; also known as thyrotrophin), luteinising hormone (LH) and follicle-stimulating hormone (FSH) produced by the basophilic cells of the anterior pituitary were elevated in a time-dependent manner. Among these hormones, TSH was the first to undergo a significant change, whereas adrenocorticotrophic hormone (ACTH), another hormone produced by basophilic cells, was not changed significantly. As the duration of cholesterol feeding increased, cholesterol deposition increased gradually in the pituitary. Histologically, basophilic cells, and especially thyrotrophs and gonadotrophs, showed an obvious increase in cell area, as well as a potential increase in their proportion of total pituitary cells. Expression of the β-subunit of TSH, FSH and LH, which controls hormone specificity and activity, exhibited a corresponding increase. In the epidemiological study, we found a similar elevation of serum TSH, LH and FSH and a decrease in ACTH in patients with hypercholesterolaemia. Significant positive correlations existed between serum total cholesterol and TSH, FSH or LH, even after adjusting for confounding factors. Taken together, the results of the present study suggest that the high-cholesterol diet affected the levels of hormones derived from anterior pituitary basophilic cells. This phenomenon might contribute to the pituitary functional disturbances described in hypercholesterolaemia.

  20. Hormone impostors

    SciTech Connect

    Colborn, T.; Dumanoski, D.; Myers, J.P.

    1997-01-01

    This article discusses the accumulating evidence that some synthetic chemicals disrupt hormones in one way or another. Some mimic estrogen and others interfere with other parts of the body`s control or endocrine system such as testosterone and thyroid metabolism. Included are PCBs, dioxins, furans, atrazine, DDT. Several short sidebars highlight areas where there are or have been particular problems.

  1. A Novel Medical Treatment of Cushing's Due to Ectopic ACTH in a Patient With Neurofibromatosis Type 1

    PubMed Central

    Bano, Gul; Mir, Farheen; Beharry, Nigel; Wilson, Philip; Hodgson, Shirley; Schey, Stephen

    2012-01-01

    A 64-year-old male presented with neurofibromatosis 1 and Cushing’s syndrome. Clinically he was over weight, depressed with extensive skin bruising and hypertension. His 24 hours urinary metanephrines, urinary 5HIAA, gut peptides and chromgranin levels were normal. His renal function and renal MRI scan was also normal. His cortisol failed to suppress on overnight dexamethsone suppression test. His low dose dexamethasone suppression with CRH stimulation showed failure of suppression of cortisol to < 50 nmol/L and ACTH was measurable at 10 ng/L on day 3. There was no response of ACTH or cortisol to CRH stimulation. His ACTH precursors were high at 126 pmol/L consistent with defective pro-opiomelanocortin (POMC) processing suggesting an ectopic source of ACTH production. The MRI scan of his pituitary and CT scan of the adrenal glands was normal. His octreotide scan was negative. The source of his ectopic ACTH was most likely a large retroperitoneal plexiform neurofibroma seen on CT abdomen that had undergone malignant peripheral nerve sheath tumour transformation on histology. He was a poor surgical risk for tumour debulking procedure. In view of the available literature and role of c-kit signalling in neurofibromatosis, he was treated with Imitinib. Four months after the treatment his Cushings had resolved on biochemical testing. After a year his plexiform neurofibroma has not increased in size. To our knowledge, this is the first case of NF1 associated with clinical and biochemical features of Cushing’s secondary to ectopic ACTH due to MPNST in a plexiform neurofibroma and its resolution on treatment with imatinib. PMID:23853621

  2. A Novel Medical Treatment of Cushing's Due to Ectopic ACTH in a Patient With Neurofibromatosis Type 1.

    PubMed

    Bano, Gul; Mir, Farheen; Beharry, Nigel; Wilson, Philip; Hodgson, Shirley; Schey, Stephen

    2013-01-01

    A 64-year-old male presented with neurofibromatosis 1 and Cushing's syndrome. Clinically he was over weight, depressed with extensive skin bruising and hypertension. His 24 hours urinary metanephrines, urinary 5HIAA, gut peptides and chromgranin levels were normal. His renal function and renal MRI scan was also normal. His cortisol failed to suppress on overnight dexamethsone suppression test. His low dose dexamethasone suppression with CRH stimulation showed failure of suppression of cortisol to < 50 nmol/L and ACTH was measurable at 10 ng/L on day 3. There was no response of ACTH or cortisol to CRH stimulation. His ACTH precursors were high at 126 pmol/L consistent with defective pro-opiomelanocortin (POMC) processing suggesting an ectopic source of ACTH production. The MRI scan of his pituitary and CT scan of the adrenal glands was normal. His octreotide scan was negative. The source of his ectopic ACTH was most likely a large retroperitoneal plexiform neurofibroma seen on CT abdomen that had undergone malignant peripheral nerve sheath tumour transformation on histology. He was a poor surgical risk for tumour debulking procedure. In view of the available literature and role of c-kit signalling in neurofibromatosis, he was treated with Imitinib. Four months after the treatment his Cushings had resolved on biochemical testing. After a year his plexiform neurofibroma has not increased in size. To our knowledge, this is the first case of NF1 associated with clinical and biochemical features of Cushing's secondary to ectopic ACTH due to MPNST in a plexiform neurofibroma and its resolution on treatment with imatinib.

  3. Clinical features of congenital adrenal insufficiency including growth patterns and significance of ACTH stimulation test.

    PubMed

    Koh, Ji Won; Kim, Gu Hwan; Yoo, Han Wook; Yu, Jeesuk

    2013-11-01

    Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency.

  4. Clinical Features of Congenital Adrenal Insufficiency Including Growth Patterns and Significance of ACTH Stimulation Test

    PubMed Central

    Koh, Ji Won; Kim, Gu Hwan; Yoo, Han Wook

    2013-01-01

    Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency. PMID:24265530

  5. ACTH and Polymorphisms at Steroidogenic Loci as Determinants of Aldosterone Secretion and Blood Pressure

    PubMed Central

    MacKenzie, Scott M.; Freel, E. Marie; Connell, John M.; Fraser, Robert; Davies, Eleanor

    2017-01-01

    The majority of genes contributing to the heritable component of blood pressure remain unidentified, but there is substantial evidence to suggest that common polymorphisms at loci involved in the biosynthesis of the corticosteroids aldosterone and cortisol are important. This view is supported by data from genome-wide association studies that consistently link the CYP17A1 locus to blood pressure. In this review article, we describe common polymorphisms at three steroidogenic loci (CYP11B2, CYP11B1 and CYP17A1) that alter gene transcription efficiency and levels of key steroids, including aldosterone. However, the mechanism by which this occurs remains unclear. While the renin angiotensin system is rightly regarded as the major driver of aldosterone secretion, there is increasing evidence that the contribution of corticotropin (ACTH) is also significant. In light of this, we propose that the differential response of variant CYP11B2, CYP11B1 and CYP17A1 genes to ACTH is an important determinant of blood pressure, tending to predispose individuals with an unfavourable genotype to hypertension. PMID:28272372

  6. ICA Occlusion by an ACTH-secreting pituitary adenoma post-TSS and irradiation

    PubMed Central

    El-Zammar, Diala; Akagami, Ryojo

    2011-01-01

    Occlusion of intracranial arteries by a pituitary adenoma with ensuing infarction is a rare occurrence. In this case study, we show the instance of a pituitary macroadenoma and apoplexy causing mechanical obstruction of the internal carotid artery with consequent infarction following transphenoidal surgery (TSS) and radiation therapy in a patient with Cushing's disease. We report a 44-year-old woman presented with amenorrhea and headaches. Necessary investigations, resection by TSS, and microscopic examination revealed an adenocorticotropin (ACTH)-secreting pituitary macroadenoma. The pituitary tumour recurred in subsequent years, resulting in the development of Cushing's disease and syndrome. Despite two more transphenoidal surgeries, radiotherapy, and medical suppressive therapy, the pituitary adenoma continued to enlarge, and the hypercortisolemia and Cushingoid symptoms persisted. A craniotomy was arranged as the next step in the treatment strategy. Only hours prior to the scheduled surgery, the patient developed left-sided hemiplegia, was diagnosed with acute occlusion of the right ICA and underwent an emergency bifrontal craniotomy with evacuation of the tumour and decompression. Pathological examination revealed evidence of apoplexy in the ACTH-secreting pituitary adenoma. This case demonstrates the vast scope of complications that can arise from pituitary adenomas despite combination therapy and forewarns clinicians to be prepared to manage these infrequent but conceivable occurrences. PMID:22399870

  7. Inactivation of the DMH selectively inhibits the ACTH and corticosterone responses to hypoglycemia.

    PubMed

    Evans, Scott B; Wilkinson, Charles W; Gronbeck, Pam; Bennett, Jennifer L; Zavosh, Aryana; Taborsky, Gerald J; Figlewicz, Dianne P

    2004-01-01

    We have previously reported that repeated bouts of insulin-induced hypoglycemia (IIH) in the rat result in blunted activation of the paraventricular, arcuate, and dorsomedial hypothalamic (DMH) nuclei. Because DMH activation has been implicated in the sympathoadrenal and hypothalamic-pituitary-adrenal (HPA) responses to stressors, we hypothesized that its blunted activation may play a role in the impaired counterregulatory response that is also observed with repeated bouts of IIH. In the present study, we evaluated the role of normal DMH activation in the counterregulatory response to a single bout of IIH. Local infusion of lidocaine (n = 8) to inactivate the DMH during a 2-h bout of IIH resulted in a significant overall decrease of the ACTH response and a delay of onset of the corticosterone response compared with vehicle-infused controls (n = 9). We observed suppression of the ACTH response at time (t) = 90 and 120 min (50 +/- 12 and 63 +/- 6%, respectively, of control levels) and early suppression of the corticosterone response at t = 30 min (59 +/- 13% of the control level). The epinephrine, norepinephrine, and glucagon responses were not altered by DMH inactivation. Our finding suggests that DMH inactivation may play a specific role in decreasing the HPA axis response after repeated bouts of IIH.

  8. ACTH4 -10, Substance P, and Dizolcipine (Mk-801) Accelerate Functional Recovery After Hemilabyrinthectomy in Goldfish

    PubMed Central

    Mattioli, R.; Huston, J. P.; Spieler, R. E.

    2000-01-01

    In this study, we evaluated the goldfish model of hemilabyrinthectomy for investigating potential recovery-promoting drugs. In this lesion model, the unilateral removal of the labyrinth induces a postural imbalance in response to light (Dorsal Light Reflex), from which the animals can recover over time. The behavioral effects of two neuropeptides were tested–namely, of substance P and ACTH4-10, both of which are known to promote functional recovery in several other lesion models. Furthermore, the effect of MK- 801, an antagonist of the glutamatergic NMDAreceptor subtype, was tested because this substance has also been shown to exert a neuroprotective effect. After lesion of the right labyrinth, the animals (n=12) were treated intraperitoneally daily either with vehicle (n=12), substance P (n=11), ACTH4-10 (n=12), or MK- 801 (n=12). Another group (n=11), which served as a non-lesion control, did not receive hemilabyrinthectomy or systemic injections. The lesion group, treated post-operatively with vehicle, did not recover from the postural deviation over the 24-d testing period. In contrast, all three test substances accelerated the functional recovery after unilateral labyrinthectomy. The decrease of the dorsal light reflex persisted even after cessation of drug treatment after 20d. The results indicate that using the dorsal light reflex in the model of hemilabyrinthectomy in goldfish provides a useful approach to studying the ability of potential new neurotrophic or neuroprotective drugs to promote functional recovery. PMID:11486488

  9. Cushing's storm secondary to a rare case of ectopic ACTH secreting metastatic breast cancer

    PubMed Central

    Bucciarelli, Maura; Lee, Ya-Yu

    2015-01-01

    Summary Ectopic ACTH secretion from breast cancer is extremely rare. We report a case of a 30-year-old woman with a history of breast cancer, who presented with psychosis and paranoid behaviour. CT of the head showed white matter disease consistent with posterior reversible encephalopathy syndrome (PRES). Despite using mifepristone with multiple antihypertensives including lisinopril, spironolactone and metoprolol, she was hypertensive. Transaminitis did not allow mifepristone dose escalation and ketoconazole utilization. Etomidate infusion at a non-sedating dose in the intensive care unit controlled her hypertension and cortisol levels. She was transitioned to metyrapone and spironolactone. She was discharged from the hospital on metyrapone with spironolactone and underwent chemotherapy. She died 9 months later after she rapidly redeveloped Cushing's syndrome and had progressive metastatic breast cancer involving multiple bones, liver and lungs causing respiratory failure. Learning points Cushing's syndrome from ectopic ACTH secreting breast cancer is extremely rare.Cushing's syndrome causing psychosis could be multifactorial including hypercortisolism and PRES.Etomidate at non-sedating doses in intensive care setting can be effective to reduce cortisol production followed by transition to oral metyrapone. PMID:26525183

  10. Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene.

    PubMed

    Mantovani, Giovanna; Maghnie, Mohamad; Weber, Giovanna; De Menis, Ernesto; Brunelli, Valeria; Cappa, Marco; Loli, Paola; Beck-Peccoz, Paolo; Spada, Anna

    2003-09-01

    Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteodystrophy. Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action [pseudohypoparathyroidism type Ia (PHP Ia)], recent studies provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad, and pituitary. The aim of this study was to investigate the presence of pituitary resistance to hypothalamic hormones acting via Gs alpha-coupled receptors in patients with PHP Ia. Six of nine patients showed an impaired GH responsiveness to GHRH plus arginine, consistent with a complete GH deficiency (GH peak from 2.6-8.6 microg/liter, normal > 16.5), and partial (GH peak 13.9 and 13.6 microg/liter) and normal responses were found in two and one patient, respectively. Accordingly, IGF-I levels were below and in the low-normal range in seven and two patients. All patients had a normal cortisol response to 1 microg ACTH test, suggesting a normal corticotroph function that was confirmed by a normal ACTH and cortisol response to CRH test in three patients. In conclusion, we report that in addition to PTH and TSH resistance, patients with PHP Ia display variable degrees of GHRH resistance, consistent with Gs alpha imprinting in human pituitary.

  11. Long-term ACTH and corticosteroid therapy in two siblings with polyneuropathy due to acute intermittent porphyria.

    PubMed

    Jusić, A; Sostarko, M; Majić, D

    1976-01-01

    The influence of long-term corticosteroid and ACTH therapy in two sisters was followed up. The periods of observation were 4 and 2 years. The high levels of corticosteroids obviously reversed the fatal progress of the disease. The relapses in the elder sister occurred during longer periods of discontinued corticosteroid therapy. In the younger the therapy was continuous. There was no relapse except for a short one appearing after the tooth extraction and discontinuation of the therapy for 10 days. Some correlation between neurological signs and symptoms and porphobilinogen androporphyrin levels were found. The question arises how it is possible to influence the genetically determined disease by corticosteroids or ACTH.

  12. Early-onset severe obesity with ACTH deficiency and red hair in a boy: the POMC deficiency.

    PubMed

    Ozen, S; Aldemir, O

    2012-01-01

    The patient is a 2.8 years old male who is extremely obese and severe hyperphagic from birth. He had seizures attacks and apnea from the second week of his life. He has red hair and serum cortisol and ACTH levels are very low. We examined our patient as a hypocortisolism due to ACTH deficiency and central hypothyrodism. After the corticosteroid replacement therapy hair color changed to brown. We performed molecular genetic analysis at the Institue for Experimental Pediatric Endocrinology laboratory in Berlin, Germany by Krude H. and found compound heterozygous mutations. As a result the case is diagnosed as POMC deficiency.

  13. Effects of (+)-8-OH-DPAT on the duration of immobility during the forced swim test and hippocampal cell proliferation in ACTH-treated rats.

    PubMed

    Miyake, Ayaka; Kitamura, Yoshihisa; Miyazaki, Ikuko; Asanuma, Masato; Sendo, Toshiaki

    2014-07-01

    In the present study, we examined the effect of ACTH on the immobilization of rats in the forced swim test and hippocampal cell proliferation after administration of the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-di-n-propylamino tetralin ((+)-8-OH-DPAT). Chronic treatment with (+)-8-OH-DPAT (0.01-0.1 mg/kg, s.c.) significantly decreased the duration of immobility in saline- and ACTH-treated rats. Chronic administration of ACTH caused a significant decrease in hippocampal cell proliferation. However, (+)-8-OH-DPAT significantly normalized cell proliferation in ACTH-treated rats. We then investigated the effects of (+)-8-OH-DPAT on the expression of brain-derived neurotrophic factor (BDNF) and cyclin D1 (elements of cyclic adenosine monophosphate response element-binding protein (CREB)-BDNF and Wnt signaling pathways, respectively) in the hippocampus of saline- and ACTH-treated rats. ACTH treatment significantly decreased the expression of cyclin D1, while treatment with (+)-8-OH-DPAT normalized the expression of cyclin D1 in ACTH-treated rats. However, the expression of BDNF did not change in either saline- or ACTH-treated rats. These findings suggest that the antidepressant effects of (+)-8-OH-DPAT in treatment-resistant animals may be attributed to an enhancement of hippocampal cell proliferation, at least in part due to an enhancement of cyclin D1 expression.

  14. In vivo correlation between c-Fos expression and corticotroph stimulation by adrenocorticotrophic hormone secretagogues in rat anterior pituitary gland.

    PubMed

    Takigami, Shu; Fujiwara, Ken; Kikuchi, Motoshi; Yashiro, Takashi

    2008-03-01

    In the anterior pituitary gland, c-Fos expression is evoked by various stimuli. However, whether c-Fos expression is directly related to the stimulation of anterior pituitary cells by hypothalamic secretagogues is unclear. To confirm whether the reception of hormone-releasing stimuli evokes c-Fos expression in anterior pituitary cells, we have examined c-Fos expression of anterior pituitary glands in rats administered with synthetic corticotrophin-releasing hormone (CRH) intravenously or subjected to restraint stress. Single intravenous administration of CRH increases the number of c-Fos-expressing cells, and this number does not change even if the dose is increased. Double-immunostaining has revealed that most of the c-Fos-expressing cells contain adrenocorticotrophic hormone (ACTH); corticotrophs that do not express c-Fos in response to CRH have also been found. However, restraint stress evokes c-Fos expression in most of the corticotrophs and in a partial population of lactotrophs. These results suggest that c-Fos expression increases in corticotrophs stimulated by ACTH secretagogues, including CRH. Furthermore, we have found restricted numbers of corticotrophs expressing c-Fos in response to CRH. Although the mechanism underlying the different responses to CRH is not apparent, c-Fos is probably a useful immunohistochemical marker for corticotrophs stimulated by ACTH secretagogues.

  15. Flow cytometry analysis of hormone receptors on human peripheral blood mononuclear cells to identify stress-induced neuroendocrine effects

    NASA Technical Reports Server (NTRS)

    Meehan, R. T.

    1986-01-01

    Understanding the role of circulating peptide hormones in the pathogenesis of space-flight induced disorders would be greatly facilitated by a method which monitors chronic levels of hormones and their effects upon in vivo cell physiology. Single and simultaneous multiparameter flow cytometry analysis was employed to identify subpopulations of mononuclear cells bearing receptors for ACTH, Endorphin, and Somatomedin-C using monoclonal antibodies and monospecific antisera with indirect immunofluorescence. Blood samples were obtained from normal donors and subjects participating in decompression chamber studies (acute stress), medical student academic examination (chronic stress), and a drug study (Dexamethasone). Preliminary results indicate most ACTH and Endorphin receptor positive cells are monocytes and B-cells, exhibit little diurnal variation but the relative percentages of receptor positive cells are influenced by exposure to various stressors and ACTH inhibition. This study demonstrates the capability of flow cytometry analysis to study cell surface hormone receptor regulation which should allow insight into neuroendocrine modulation of the immune and other cellular systems during exposure to stress or microgravity.

  16. The effects of vasoactive intestinal peptide on adrenal steroid hormone secretion

    SciTech Connect

    Cunningham, L.A.

    1988-01-01

    Vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers have been demonstrated in the rat adrenal cortex in close association with zona glomerulosa cells. We have studied the effects of VIP on steroid hormone secretion from the outer zones of the normal rat adrenal cortex. Intact capsule-glomerulosa preparations, consisting of the capsule, zona glomerulosa, and a small portion of the zona fasciculata were perifused in vitro. The secretory responsiveness was assessed by measuring aldosterone and corticosterone release following stimulation with the physiological secretagogues ACTH and angiotensin II. The distribution of adrenal VIP receptors was assessed by in vitro autoradiography of {sup 125}I-VIP binding. {sup 125}I-VIP (0.75 and 2.0 nM) binding was concentrated in the capsule and zone glomerulosa, coincident with the distribution of VIP nerve fibers which aborize extensively in this region. The specificity of this binding was demonstrated using unlabelled VIP, ACTH and angiotensin II.

  17. Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers.

    PubMed

    Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

    2013-01-01

    Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus-pituitary-adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30-64 years): a low-dose adrenocorticotrophic hormone (ACTH(1-24), Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone-corticotropin releasing hormone (DEX-CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at - 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort-reward-imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX-CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis.

  18. Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones

    PubMed Central

    Senovilla, Laura; Núñez, Lucía; de Campos, José María; de Luis, Daniel A.; Romero, Enrique; García-Sancho, Javier; Villalobos, Carlos

    2015-01-01

    Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs. PMID:26106585

  19. A polymorphic form of steroidogenic factor 1 associated with ACTH receptor deficiency in mouse adrenal cell mutants.

    PubMed

    Schimmer, Bernard P; Cordova, Martha; Tsao, Jennivine; Frigeri, Claudia

    2003-06-01

    We have described a family of adrenocortical tumor cell mutants (including clones OS3, Y6, and 10r9) that are resistant to ACTH because they fail to express the gene encoding the ACTH receptor (MC2R). The MC2R deficiency results from a mutation that impairs the activity of the nuclear receptor steroidogenic factor 1 (SF1) at the MC2R promoter. In this report, we show that ACTH resistance in the mutant clones is associated with a Sf1 gene that has Ser at codon 172 instead of Ala. In two of the three mutant clones, this Sf1 allele is amplified together with flanking DNA from chromosome 2 that includes the genes encoding germ cell nuclear factor and the beta-type proteosome subunit Psmb7. SF1(A172) and SF1(S172) exhibit little or no difference in transcriptional activity in SF1-dependent reporter gene assays, suggesting that SF1(S172) per se is not directly responsible for the loss of MC2R expression. Instead, the Sf1(S172) allele appears to be a marker of ACTH resistance in this family of adrenocortical tumor cell mutants, possibly reflecting the activity of a neighboring gene.

  20. [Effect of dalargin on the content of endorphins, leucine-enkephalin ACTH and corticosterone of the blood of stressed rats].

    PubMed

    Bobkov, A I; Polonskiĭ, V M; Vinogradov, V A; Demina, D G; Smagin, V G

    1985-12-01

    Stress caused by acute cysteamine duodenal ulcer was induced in Wistar male rats. All the endogenous opioides under study were involved in the stress-reaction mechanism. Protective dalargin (synthetic enkephalin analogue) administration revealed a tendency towards normalization of endorphin, L-enkephalin and ACTH blood levels.

  1. The physiological consequences of crib-biting in horses in response to an ACTH challenge test.

    PubMed

    Briefer Freymond, S; Bardou, D; Briefer, E F; Bruckmaier, R; Fouché, N; Fleury, J; Maigrot, A-L; Ramseyer, A; Zuberbühler, K; Bachmann, I

    2015-11-01

    Stereotypies are repetitive and relatively invariant patterns of behavior, which are observed in a wide range of species in captivity. Stereotypic behavior occurs when environmental demands produce a physiological response that, if sustained for an extended period, exceeds the natural physiological regulatory capacity of the organism, particularly in situations that include unpredictability and uncontrollability. One hypothesis is that stereotypic behavior functions to cope with stressful environments, but the existing evidence is contradictory. To address the coping hypothesis of stereotypies, we triggered physiological reactions in 22 horses affected by stereotypic behavior (crib-biters) and 21 non-crib-biters (controls), using an ACTH challenge test. Following administration of an ACTH injection, we measured saliva cortisol every 30 min and heart rate (HR) continuously for a period of 3h. We did not find any differences in HR or HR variability between the two groups, but crib-biters (Group CB) had significantly higher cortisol responses than controls (Group C; mean ± SD: CB, 5.84 ± 2.62 ng/ml, C, 4.76 ± 3.04 ng/ml). Moreover, crib-biters that did not perform the stereotypic behavior during the 3-hour test period (Group B) had significantly higher cortisol levels than controls, which was not the case of crib-biters showing stereotypic behavior (Group A) (B, 6.44 ± 2.38 ng/ml A, 5.58 ± 2.69 ng/ml). Our results suggest that crib-biting is a coping strategy that helps stereotypic individuals to reduce cortisol levels caused by stressful situations. We conclude that preventing stereotypic horses from crib-biting could be an inappropriate strategy to control this abnormal behavior, as it prevents individuals from coping with situations that they perceive as stressful.

  2. The Role of ACTH and Corticosteroids for Sepsis and Septic Shock: An Update

    PubMed Central

    Annane, Djillali

    2016-01-01

    Sepsis is a common disorder associated with high morbidity and mortality. It is now defined as an abnormal host response to infection, resulting in life-threatening dysfunction of organs. There is evidence from in vitro and in vivo experiments in various animal models and in patients that endotoxin or sepsis may directly and indirectly alter the hypothalamic–pituitary–adrenal response to severe infection. These alterations may include necrosis or hemorrhage or inflammatory mediator-mediated decreased ACTH synthesis, steroidogenesis, cortisol delivery to tissues, clearance from plasma, and decreased sensitivity of tissues to cortisol. Disruption of the hypothalamic–pituitary–adrenal axis may translate in patients with sepsis into cardiovascular and other organ dysfunction, and eventually an increase in the risk of death. Exogenous administration of corticosteroids at moderate dose, i.e., <400 mg of hydrocortisone or equivalent for >96 h, may help reversing sepsis-associated shock and organ dysfunction. Corticosteroids may also shorten the duration of stay in the ICU. Except for increased blood glucose and sodium levels, treatment with corticosteroids was rather well tolerated in the context of clinical trials. The benefit of treatment on survival remains controversial. Based on available randomized controlled trials, the likelihood of survival benefit is greater in septic shock versus sepsis patients, in sepsis with acute respiratory distress syndrome or with community-acquired pneumonia versus patients without these conditions, and in patients with a blunted cortisol response to 250 μg of ACTH test versus those with normal response. PMID:27379022

  3. Neurotrophic ACTH4-9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis.

    PubMed

    Duckers, H J; van Dokkum, R P; Verhaagen, J; van Luijtelaar, E L; Coenen, A M; Lopes da Silva, F H; Gispen, W H

    1998-12-01

    Chronic experimental allergic encephalomyelitis (CEAE) is an established experimental model for multiple sclerosis (MS). The demyelinating lesions in the white matter of the central nervous system observed in CEAE and in MS are accompanied by various neurophysiological alterations. Among the best defined electrophysiological abnormalities are the changes in event-related potentials, in particular evoked potentials involving the spinal cord, i.e. motor and sensory evoked potentials. Less familiar are the changes observed in the electroencephalogram of CEAE-affected animals, which are also encountered in the human equivalent, MS. In the present experiment we evaluated the therapeutic value of a neurotrophic peptide treatment [H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH, an ACTH4-9 analogue] and its effect on the delayed flash visual evoked potentials (VEP) and power spectra of the electroencephalogram, during a 17-week follow-up of CEAE. CEAE animals treated with the neurotrophic peptide were protected against the development of neurological symptoms during the course of the demyelinating syndrome. VEPs of animals suffering from CEAE showed a delay of the latencies of the late components which was significantly counteracted by peptide treatment. The peak-to-peak amplitude of the VEP afterdischarge recorded from CEAE animals was significantly increased during the course of CEAE and correlated closely with the progression of the myelinopathy. Furthermore, CEAE animals showed an increase of electroencephalogram (EEG) beta activity of up to 500% as compared with the age-matched control group. This increase in beta power mainly consisted of a prevailing 20-21 Hz peak, a frequency that normally is not dominant in control EEG recordings of the rat during passive wakefulness. All these electrophysiological phenomena were absent in ACTH4-9 analogue-treated animals. The present findings underscore the potential importance of a neurotrophic peptide treatment in the pharmacotherapy of

  4. Diagnosis and Treatment of Hypopituitarism

    PubMed Central

    2015-01-01

    Hypopituitarism is a chronic endocrine illness that caused by varied etiologies. Clinical manifestations of hypopituitarism are variable, often insidious in onset and dependent on the degree and severity of hormone deficiency. However, it is associated with increased mortality and morbidity. Therefore, early diagnosis and prompt treatment is necessary. Hypopituitarism can be easily diagnosed by measuring basal pituitary and target hormone levels except growth hormone (GH) and adrenocorticotropic hormone (ACTH) deficiency. Dynamic stimulation tests are indicated in equivocal basal hormone levels and GH/ACTH deficiency. Knowledge of the use and limitations of these stimulation tests is mandatory for proper interpretation. It is necessary for physicians to inform their patients that they may require lifetime treatment. Hormone replacement therapy should be individualized according to the specific needs of each patient, taking into account possible interactions. Long-term endocrinological follow-up of hypopituitary patients is important to monitor hormonal replacement regimes and avoid under- or overtreatment. PMID:26790380

  5. The effects of hypokalaemia on the hormone exocytosis in adenohypophysis and prolactinoma cell culture model systems.

    PubMed

    Molnár, Z; Pálföldi, R; László, A; Radács, M; László, M; Hausinger, P; Tiszlavicz, L; Rázga, Z; Valkusz, Z; Gálfi, M

    2014-11-01

    The extracellular ion milieu determines the exocytosis mechanism that is coupled to spontaneous electrical activity. The K(+) ion plays crucial role in this mechanism: as the potassium current is associated with membrane hyperpolarization and hormone release through protein cascade activation. The primary aim of this study was to investigate the response mechanisms of normal adenohypophysis and adenohypophyseal prolactinoma cell populations at different extracellular K(+) levels with an otherwise isoionic milieu of all other essential ions. We focused on prolactin (PRL) and adrenocorticotrophic hormone (ACTH) release.In our experimental study, female Wistar rats (n=20) were treated with estrone-acetate (150 μg/kg b.w./week) for 6 months to induce prolactinomas in the adenohypophysis. Primary, monolayer cell cultures were prepared by enzymatic and mechanical digestion. PRL and ACTH hormone presence was measured by radioimmunoassay or immuno-chemiluminescence assay. Immunocytochemistry was used to assess the apoptotic cells.Differences between the effects of hypokalaemia on normal adenohypophysis cultures and prolactinoma cell populations were investigated. Significant alteration (p<0.001, n=10) in hormone exocytosis was detected in K(+) treated adenohypophyseal and prolactinoma cell cultures compared to untreated groups. Immunocyto-chemistry showed that Bcl-2 expression was reduced under hypokalaemic conditions.The decrease in hormone exocytosis was tightly correlated to the extracellular K(+) in both cell types, leading to the conclusion that external K(+) may be the major factor for the inhibition of hormone release. The significant increase in hormone content in supernatant media suggests that hypokalaemia may play important role in apoptosis.

  6. Effect of Novel Melanocortin Type 2 Receptor Antagonists on the Corticosterone Response to ACTH in the Neonatal Rat Adrenal Gland In Vivo and In Vitro

    PubMed Central

    Nensey, Nasha K.; Bodager, Jonathan; Gehrand, Ashley L.; Raff, Hershel

    2016-01-01

    Stress-induced increases in neonatal corticosterone demonstrate a unique shift from ACTH independence to ACTH dependence between postnatal day 2 (PD2) and day 8 (PD8) in newborn rats. This shift could be due to the binding of a bioactive, non-­immunoreactive plasma ligand to the adrenocortical melanocortin 2 receptor (MC2R) (ACTH receptor). A potent MC2R antagonist would be useful to evaluate this phenomenon in the neonate. Therefore, we investigated the acute corticosterone response to ACTH(1–39) injection in rat pups pretreated with newly developed MC2R antagonists (GPS1573 and GPS1574), which have not been tested in vivo. The doses used in vivo were based on their in vitro potency, with GP1573 being more potent than GPS1574. GPS1573 (PD2 and PD8), GPS1574 (PD2 only), or vehicle were injected intraperitoneally (ip) 10 min before baseline sampling. Then, 0.001 mg/kg of ACTH(1–39) was injected ip, and subsequent blood samples obtained for the measurement of plasma corticosterone. Pretreatment of PD2 pups with GPS1573 demonstrated augmentation, rather than inhibition, of the corticosterone response to ACTH. In PD8 pups, pretreatment with 0.1 mg/kg GPS1573, but not 4 mg/kg, augmented the corticosterone response to ACTH. Pretreatment with GPS1574 attenuated the plasma corticosterone response to ACTH at 30 min in PD2 pups. The activity of these two compounds in vivo do not match their potency in vitro, with GPS1573 leading to a small augmentation of the corticosterone response to ACTH in vivo while GPS1574 resulted in inhibition. PMID:27047449

  7. Effects of melanocortins on fetal development.

    PubMed

    Simamura, Eriko; Shimada, Hiroki; Shoji, Hiroki; Otani, Hiroki; Hatta, Toshihisa

    2011-06-01

    Melanocortins, adrenocorticotropic hormone (ACTH) and α-, β-, and γ-melanocyte-stimulating hormone (MSH) are produced in the placenta and secreted into embryos/fetuses. ACTH concentrations are higher in fetal plasma than in maternal plasma and peak at mid-gestation in rats, whereas ACTH production starts in the anterior lobe of the fetal pituitary at later stages. Melanocortin receptors (MC1-5R), receptors for ACTH and α-, β- and γ-MSH, are expressed in various adult organs. The specific function of these receptors has been well examined in the hypothalamic-pituitary-adrenocortical (HPA) axis and the HPA axis-like network in the skin, and anti-inflammatory effects for white blood cells have also been investigated. MC2R and/or MC5R are also expressed in the testis, lung, kidney, adrenal, liver, pancreas, brain and blood cells at different stages in mouse and rat embryos/fetuses. Melanocortins in embryos and fetuses promote maturation of the HPA axis and also contribute to the development of lung, testis, brain and blood cells. Recently, a unique ACTH function was revealed in fetuses: placental ACTH, which is secreted by the maternal leukemia inhibitory factor (LIF), and induces LIF secretion from fetal nucleated red blood cells. Finally, the maternal LIF-placental ACTH-fetal LIF signal relay regulates the LIF level and promotes neurogenesis in fetuses, which suggests that ACTH acts as a signal transducer or effector for fetal development in the maternal-fetal signal pathway.

  8. Effects of withholding feed on thyrotropin-releasing hormone stimulation test results and effects of combined testing on oral sugar test and thyrotropin-releasing hormone stimulation test results in horses.

    PubMed

    Restifo, Melissa M; Frank, Nicholas; Hermida, Pilar; Sanchez-Londoño, Alfredo

    2016-07-01

    OBJECTIVE To assess effects of withholding feed on thyrotropin-releasing hormone (TRH) stimulation test results used in diagnosis of pituitary pars intermedia dysfunction in horses and determine effects of combined testing on results of the TRH stimulation test and the oral sugar test (OST) used in diagnosis of equine metabolic syndrome. ANIMALS 30 adult horses. PROCEDURES All horses underwent TRH stimulation tests under fed and nonfed conditions, an OST alone, and an OST combined with TRH stimulation testing. For TRH stimulation tests, plasma ACTH concentrations were measured before (baseline) and 10 minutes after (poststimulation) IV TRH administration. For the OST, plasma glucose and insulin concentrations were measured before (baseline) and 60 and 90 minutes after oral corn syrup administration. For combined testing, the TRH stimulation test was initiated immediately after 60-minute posttreatment sample collection for the OST. Results were compared among methods by Wilcoxon matched-pairs, signed rank tests, paired t tests, and Bland-Altman analysis. RESULTS Feeding conditions did not affect median ACTH concentrations when TRH stimulation tests were performed alone. Median baseline ACTH concentration did not differ between TRH stimulation tests performed alone (under fed or nonfed conditions) and those combined with OSTs. Median poststimulation ACTH concentration was significantly lower for combined tests than for solitary TRH stimulation tests. Mean 60-minute plasma glucose concentration was significantly lower for solitary OSTs than for combined tests, but this difference could not be attributed to TRH administration. CONCLUSIONS AND CLINICAL RELEVANCE Combined testing in the manner described impacted ACTH concentrations during TRH stimulation tests and is not recommended at this time.

  9. [Pulmonary Carcinoid Tumor with Cushing's Syndrome in a Patient who Underwent Pulmonary Resection by Video-Assisted Thoracic Surgery;Report of a Case].

    PubMed

    Sato, Hiroshi; Mishina, Taijiro; Miyajima, Masahiro; Watanabe, Atsushi

    2015-07-01

    Pulmonary carcinoid tumor with Cushing's syndrome is comparatively rare disease. It is difficult to make an early diagnosis due to small size lesion in its early stage. We report a case of pulmonary carcinoid tumor with Cushing's syndrome successfully localised by positron emission tomography/computed tomography and was resected in the early stage. The levels of serum cortisol and adrenocorticotropic hormone( ACTH) decreased immediately after surgery, and the symptoms of Cushing's syndrome were relieved.

  10. Effect of noise pollution on testicular tissue and hormonal assessment in rat.

    PubMed

    Farzadinia, P; Bigdeli, M; Akbarzadeh, S; Mohammadi, M; Daneshi, A; Bargahi, A

    2016-11-01

    Many studies have focused on the effect of noise stress on the health. So far, few studies have been conducted on the effect of noise on reproductive system. The aim of study was to investigate the effect of noise pollution on morphometric parameters of testicular tissue and hormonal assessment (ACTH, cortisol and testosterone). In this study, 40 male rats were exposed to control, 95, 105 and 115 dB noise intensity for sixty days. At the end of study, blood sampling was performed and ACTH, cortisol and testosterone concentrations were assessed. The results showed that noise stress decreased testosterone levels in the 115 dB-treated group, while it increased the ACTH and cortisol levels. Histological sections of testis showed that the mean diameter of the seminiferous tubules and thickness of the germinal epithelium reduced compared to the control group. Also the ratio of the interstitial tissue area to the total testicular tissue area was increased significantly. Our study shows that noise stress may have negative influences on male fertility.

  11. Mood alteration from treadmill running and its relationship to beta-endorphin, corticotropin, and growth hormone.

    PubMed

    Kraemer, R R; Dzewaltowski, D A; Blair, M S; Rinehardt, K F; Castracane, V D

    1990-09-01

    We examined the effects of running on mood alteration in males and females and its relationship to changes in beta-endorphin (B-EN), corticotropin (ACTH), and growth hormone (GH). Thirteen males and ten females ran on a treadmill for 30 min at 80% of previously determined maximum heart rate. Five plasma samples were obtained through an indwelling catheter before exercise (-30 and 0 min), during exercise (15 min), at exercise completion (+30 min), and after 30 min of recovery (R30); the Profile of Mood States (POMS) inventory was administered at -30 and +30. Composite mood improved after the run for both males and females withput concomitant rise in B-EN. For males but not females, an increase in mood was associated with lower B-EN (r = 0.65) and ACTH (r = 0.65) and this relationship was also significant prior to exercise for B-EN (r = 0.74) and ACTH (r = 0.81). It appears that an increase in peripheral beta-endorphin concentration may not be a major contributor to improved mood in response to exercise, but is an indicator of negative mood in males.

  12. Deciding about hormone therapy

    MedlinePlus

    HRT - deciding; Estrogen replacement therapy - deciding; ERT- deciding; Hormone replacement therapy - deciding; Menopause - deciding; HT - deciding; Menopausal hormone therapy - deciding; MHT - deciding

  13. Noninvasive measurement of steroid hormones in zebrafish holding-water.

    PubMed

    Félix, Ana S; Faustino, Ana I; Cabral, Eduarda M; Oliveira, Rui F

    2013-03-01

    Zebrafish (Danio rerio) has recently emerged as a new animal model in neuroendocrinology and behavior (e.g., stress physiology and ecotoxicology studies). In these areas, the concentrations of steroid hormones in the blood are often used to study the endocrinological status of individuals. However, due to the small body size of zebrafish, blood sampling is difficult to perform and the amount of plasma obtained per sample for assaying hormones is very small (ca. 1-5 μL), and therefore most studies have been using whole-body hormone concentrations, which implies sacrificing the individuals and hampers sequential sampling of the same individual. Here a noninvasive method to assay steroid hormones from zebrafish holding-water, based on the fact that steroids are released into the fish holding-water through the gills by passive diffusion, is validated. Cortisol and the androgen 11-ketotestosterone (KT) were measured in water samples and compared to plasma levels in the same individuals. Cortisol released to holding-water correlates positively with plasma concentrations, but there was a lack of correlation between KT water and circulating levels. However, KT levels showed a highly significant sex difference that can be used to noninvasively sex individuals. An ACTH challenge test demonstrated that an induced increase in circulating cortisol concentration can be reliably detected in holding-water levels, hence attesting the responsiveness of holding-water levels to fluctuations in circulating levels.

  14. Noninvasive Measurement of Steroid Hormones in Zebrafish Holding-Water

    PubMed Central

    Félix, Ana S.; Faustino, Ana I.; Cabral, Eduarda M.

    2013-01-01

    Abstract Zebrafish (Danio rerio) has recently emerged as a new animal model in neuroendocrinology and behavior (e.g., stress physiology and ecotoxicology studies). In these areas, the concentrations of steroid hormones in the blood are often used to study the endocrinological status of individuals. However, due to the small body size of zebrafish, blood sampling is difficult to perform and the amount of plasma obtained per sample for assaying hormones is very small (ca. 1–5 μL), and therefore most studies have been using whole-body hormone concentrations, which implies sacrificing the individuals and hampers sequential sampling of the same individual. Here a noninvasive method to assay steroid hormones from zebrafish holding-water, based on the fact that steroids are released into the fish holding-water through the gills by passive diffusion, is validated. Cortisol and the androgen 11-ketotestosterone (KT) were measured in water samples and compared to plasma levels in the same individuals. Cortisol released to holding-water correlates positively with plasma concentrations, but there was a lack of correlation between KT water and circulating levels. However, KT levels showed a highly significant sex difference that can be used to noninvasively sex individuals. An ACTH challenge test demonstrated that an induced increase in circulating cortisol concentration can be reliably detected in holding-water levels, hence attesting the responsiveness of holding-water levels to fluctuations in circulating levels. PMID:23445429

  15. Hormonal status and fluid electrolyte metabolism in motion sickness

    SciTech Connect

    Grigoriev, A.I.; Nichiporuk, I.A.; Yasnetsov, V.V.; Shashkov, V.S.

    1988-04-01

    In the first experimental series, 10 healthy male test subjects with a high susceptibility to motion sickness showed a significant increase of ACTH, cortisol, STH, prolactin, ADH, aldosterone concentrations, and plasma renin activity after vestibular tests. The 10 subjects with a moderate susceptibility exhibited a still higher increase of the hormones, except plasma renin. The 8 test subjects with a low susceptibility displayed a considerable increase in ACTH, cortisol, and STH after vestibular stimulation. In the second experimental series, the increase of STH, cortisol, ADH, aldosterone and renin occurred immediately after rotation in the moderate susceptibility subjects and an hour after exposure in the high susceptibility subjects. This may be indicative of specific immediate adaptation mechanisms or excitation transfer in the CNS in high susceptibility persons. In the third experimental animal series, the permeability of the blood-brain barrier for /sup 125/I and IgG increased after rotation. Greater concentrations of potassium, chloride, and urea in CSF are suggestive of an inhibition process activation in the CNS and, probably, of an active urea transport by the vascular plexus epithelium which maintains constant osmotic pressure of cerebral extracellular fluid and prevents hyper-hydration of CNS neurons.

  16. Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture

    SciTech Connect

    Cronin, M.J.; Evans, W.S.; Rogol, A.D.; Weiss, A.A.; Thorner, M.O.; Orth, D.N.; Nicholson, W.E.; Yasumoto, T.; Hewlett, E.L.

    1986-08-01

    Bordetella pertussis synthesis a variety of virulence factors including a calmodulin-dependent adenylate cyclase (AC) toxin. Treatment of anterior pituitary cells with this AC toxin resulted in an increase in cellular cAMP levels that was associated with accelerated exocytosis of growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH). The kinetics of release of these hormones, however, were markedly different; GH and prolactin were rapidly released, while LH and ACTH secretion was more gradually elevated. Neither dopamine agonists nor somatostatin changes the ability of AC toxin to generate cAMP (up to 2 h). Low concentrations of AC toxin amplified the secretory response to hypophysiotrophic hormones. The authors conclude that bacterial AC toxin can rapidly elevate cAMP levels in anterior pituitary cells and that it is the response that explains the subsequent acceleration of hormone release.

  17. Hypopituitarism.

    PubMed

    Higham, Claire E; Johannsson, Gudmundur; Shalet, Stephen M

    2016-11-12

    Hypopituitarism refers to deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Hypopituitarism is associated with excess mortality, a key risk factor being cortisol deficiency due to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or insidious, and the most common cause in adulthood is a pituitary adenoma, or treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed based on baseline blood sampling for thyroid stimulating hormone, gonadotropin, and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic hormone deficiency dynamic stimulation tests are usually needed. Repeated pituitary function assessment at regular intervals is needed for diagnosis of the predictable but slowly evolving forms of hypopituitarism. Replacement treatment exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone, and desmopressin. If onset is acute, cortisol deficiency should be replaced first. Modifications in replacement treatment are needed during the transition from paediatric to adult endocrine care, and during pregnancy.

  18. A novel mutation of the adrenocorticotropin receptor (ACTH-R) gene in a family with the syndrome of isolated glucocorticoid deficiency, but no ACTH-R abnormalities in two families with the triple A syndrome

    SciTech Connect

    Tsigos, C.; Arai, K.; Latronico, A.C. ||

    1995-07-01

    Isolated glucocorticoid deficiency (IGD) is an autosomal recessive disorder characterized by primary adrenocortical insufficiency, usually without mineralocorticoid deficiency. Occasionally, the disorder is associated with alacrima and achalasia of the esophagus (triple A syndrome), suggesting potential heterogeneity in its etiology. Mutations in the ACTH receptor gene have been reported in several families with IGD. We have amplified and directly sequenced the entire intronless ACTH receptor gene in 1 other family with IGD and 2 famlies with triple A syndrome. The proband with IGD was a homozygote for an A {r_arrow}G substitution, changing tyrosine 254 to cysteine in the third extracellular loop of the receptor protein, probably interfering with ligand binding. Both of her parents were heterozygotes for this mutation, which was not detected in 100 normal alleles. No mutations were identified in the entire coding area of the ACTH receptor in the 2 families with triple A syndrome, supporting the idea of a developmental or postreceptor defect in this syndrome. 19 refs., 1 fig.

  19. Hormones in the immune system and their possible role. A critical review.

    PubMed

    Csaba, György

    2014-09-01

    Immune cells synthesize, store and secrete hormones, which are identical with the hormones of the endocrine glands. These are: the POMC hormones (ACTH, endorphin), the thyroid system hormones (TRH, TSH, T3), growth hormone (GH), prolactin, melatonin, histamine, serotonin, catecholamines, GnRH, LHRH, hCG, renin, VIP, ANG II. This means that the immune cells contain all of the hormones, which were searched at all and they also have receptors for these hormones. From this point of view the immune cells are similar to the unicells (Tetrahymena), so it can be supposed that these cells retained the properties characteristic at a low level of phylogeny while other cells during the evolution accumulated to form endocrine glands. In contrast to the glandular endocrine cells, immune cells are polyproducers and polyreceivers. As they are mobile cells, they are able to transport the stored hormone to different places (packed transport) or attracted by local factors, accumulate in the neighborhood of the target, synthesizing and secreting hormones locally. This is taking place, e.g. in the case of endorphin, where the accumulating immune cells calms pain caused by the inflammation. The targeted packed transport is more economical than the hormone-pouring to the blood circulation of glandular endocrines and the targeting also cares the other receptor-bearing cells timely not needed the effect. Mostly the immune-effects of immune-cell derived hormones were studied (except endorphin), however, it is not exactly cleared, while the system could have scarcely studied important roles in other cases. The evolutionary aspects and the known as well, as possible roles of immune-endocrine system and their hormones are listed and discussed.

  20. A secretagogin locus of the mammalian hypothalamus controls stress hormone release.

    PubMed

    Romanov, Roman A; Alpár, Alán; Zhang, Ming-Dong; Zeisel, Amit; Calas, André; Landry, Marc; Fuszard, Matthew; Shirran, Sally L; Schnell, Robert; Dobolyi, Árpád; Oláh, Márk; Spence, Lauren; Mulder, Jan; Martens, Henrik; Palkovits, Miklós; Uhlen, Mathias; Sitte, Harald H; Botting, Catherine H; Wagner, Ludwig; Linnarsson, Sten; Hökfelt, Tomas; Harkany, Tibor

    2015-01-02

    A hierarchical hormonal cascade along the hypothalamic-pituitary-adrenal axis orchestrates bodily responses to stress. Although corticotropin-releasing hormone (CRH), produced by parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) and released into the portal circulation at the median eminence, is known to prime downstream hormone release, the molecular mechanism regulating phasic CRH release remains poorly understood. Here, we find a cohort of parvocellular cells interspersed with magnocellular PVN neurons expressing secretagogin. Single-cell transcriptome analysis combined with protein interactome profiling identifies secretagogin neurons as a distinct CRH-releasing neuron population reliant on secretagogin's Ca(2+) sensor properties and protein interactions with the vesicular traffic and exocytosis release machineries to liberate this key hypothalamic releasing hormone. Pharmacological tools combined with RNA interference demonstrate that secretagogin's loss of function occludes adrenocorticotropic hormone release from the pituitary and lowers peripheral corticosterone levels in response to acute stress. Cumulatively, these data define a novel secretagogin neuronal locus and molecular axis underpinning stress responsiveness.

  1. A secretagogin locus of the mammalian hypothalamus controls stress hormone release

    PubMed Central

    Romanov, Roman A; Alpár, Alán; Zhang, Ming-Dong; Zeisel, Amit; Calas, André; Landry, Marc; Fuszard, Matthew; Shirran, Sally L; Schnell, Robert; Dobolyi, Árpád; Oláh, Márk; Spence, Lauren; Mulder, Jan; Martens, Henrik; Palkovits, Miklós; Uhlen, Mathias; Sitte, Harald H; Botting, Catherine H; Wagner, Ludwig; Linnarsson, Sten; Hökfelt, Tomas; Harkany, Tibor

    2015-01-01

    A hierarchical hormonal cascade along the hypothalamic-pituitary-adrenal axis orchestrates bodily responses to stress. Although corticotropin-releasing hormone (CRH), produced by parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) and released into the portal circulation at the median eminence, is known to prime downstream hormone release, the molecular mechanism regulating phasic CRH release remains poorly understood. Here, we find a cohort of parvocellular cells interspersed with magnocellular PVN neurons expressing secretagogin. Single-cell transcriptome analysis combined with protein interactome profiling identifies secretagogin neurons as a distinct CRH-releasing neuron population reliant on secretagogin’s Ca2+ sensor properties and protein interactions with the vesicular traffic and exocytosis release machineries to liberate this key hypothalamic releasing hormone. Pharmacological tools combined with RNA interference demonstrate that secretagogin’s loss of function occludes adrenocorticotropic hormone release from the pituitary and lowers peripheral corticosterone levels in response to acute stress. Cumulatively, these data define a novel secretagogin neuronal locus and molecular axis underpinning stress responsiveness. PMID:25430741

  2. [Long-lasting behavioral effects of chronic neonatal treatment with ACTH (4-10) analogue semax in white rat pups].

    PubMed

    Sebentsova, E A; Denisenko, A V; Levitskaia, N G; Andreeva, L A; Kamenskiĭ, A A; Miasoedov, N F

    2005-01-01

    It is well known that ACTH/MSH-like peptides (melanocortins) have neurotrophic and neuroprotective effects on the central and peripheral nervous systems in the early postnatal life. The aim of present work was to study consequences of the ACTH (4-10) analogue Semax influence on the developing brain. The work was carried out in white rat pups. The peptide (0.05 mg/kg, i/p) was injected daily on the 8th-21st postnatal days. Delayed long-lasting effects of such treatment on animal behavior were revealed. At the age of four to eight weeks, Semax-treated rats displayed elevated exploratory activity, decreased anxiety level and improved passive avoidance conditioning. The results suggest that neonatal Semax administration modulates the development of the central nervous system.

  3. Personality dependent effects of the ACTH 4--10 fragment on test performances and on concomitant autonomic reactions.

    PubMed

    Breier, C; Kain, H; Konzett, H

    1979-11-01

    The effect of the ACTH-fragment 4--10 (30 mg SC) on a mental performance test and on some concomitant cardiovascular changes was investigated in comparison with a placebo in a double blind cross-over study. The subjects were either mainly extraverted or mainly introverted according to Eysenck's 'Maudsley Personality Inventory'. Under the influence of the heptapeptide extraverted subjects achieved a higher total score in the mental task performance with a smaller increase of forearm blood flow and of heart rate than under the influence of the placebo. In contrast, under the influence of the placebo introverted subjects achieved a higher total score in the mental task performance with a smaller increase of forearm blood flow and of heart rate than under the influence of the ACTH-fragment. Personality, therefore, determines to some degree how this centrally acting heptapeptide influences efficiency in the mental task performance and the concomitant cardiovascular changes.

  4. Cytoplasmic filaments of Crooke's hyaline change belong to the cytokeratin class. An immunocytochemical and ultrastructural study.

    PubMed Central

    Neumann, P. E.; Horoupian, D. S.; Goldman, J. E.; Hess, M. A.

    1984-01-01

    Crooke's hyaline change was studied by immunocytochemistry using an anti-adrenocorticotropic hormone (ACTH) antiserum and five different antisera against cytokeratins. Crooke's hyaline appears in basophil cells of the adenohypophysis in patients with hypercortisolism, presumably as a part of the negative feedback on corticotropin secretion. Previous studies have identified the hyaline material as a simple protein, apparently unrelated to ACTH, and electron microscopy has revealed a loss of secretory granules and an accumulation of 6-9-nm filaments in the cytoplasm of affected cells. In this study, the secretory granules in adenohypophysial cells exhibiting Crooke's hyaline change were labeled by anti-ACTH antibodies, while the hyaline material was positive for cytokeratin with each of the five antisera used. The results suggest that high levels of glucocorticoids may stimulate elaboration of cytokeratins in basophils while they suppress the production and release of ACTH. Images Figure 1 Figure 2 Figure 3 PMID:6205591

  5. The role of brain biogenic amines in the control of pituitary-adrenocortical activity

    NASA Technical Reports Server (NTRS)

    Maickel, R. P.

    1975-01-01

    It was found that pretreatment of animals with desmethyl imipramine antagonized the reserpine-induced sedation without preventing the decline in brain amines or the hypersecretion of adrenocorticotropic hormone (ACTH). The antagonism of reserpine-induced ACTH hypersecretion by the monoamine oxidose (MAO) inhibitor pargyline (MO 911, N-methyl-N-benzyl-2-propynylamine) was studied. Evidence is presented that this antagonism is related to the level of brain biogenic amines maintained during the course of action of the drug. Pretreatment with MAO inhibitors does not affect the ACTH hypersecretion evoked by exposure to cold or chlorpromazine, lending further support to the hypothesis that reserpine-induced ACTH hypersecretion is related to brain amine changes.

  6. A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report

    PubMed Central

    Lim, Joo Hee; Kim, Soo Jung; Jung, Mo Kyung; Kim, Ki Eun; Kwon, Ah Reum; Chae, Hyun Wook; Kim, Duk Hee

    2016-01-01

    A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS) was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease. PMID:27104179

  7. Hypokalemia associated with a solitary pulmonary nodule

    PubMed Central

    Saeian, Samira; Ghayumi, Seiyed Mohammad Ali; Shams, Mesbah

    2016-01-01

    Abstract Background: Differential diagnosis of hypokalemia and adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome often presents challenging in endocrinology and requires careful clinical, biochemical, radiological, and pathological investigations. Hypokalemia is a common abnormality and systematic approach is required to avoid delays in diagnosis of important underlying causes. Case Summary: A 49-year-old woman presented with moderate hypokalemia. Further evaluation showed hypercortisolism due to ectopic ACTH secretion. Chest computed tomography (CT) revealed a peripheral solitary pulmonary nodule. Excision biopsy of the nodule showed carcinoid tumor. After excision biopsy, all of the patient's symptoms improved and electrolytes and ACTH levels also became normal. Conclusion: Carciniod tumors should be considered as a differential diagnosis in patients presenting with hypokalemia and ectopic ACTH syndrome. Carcinoid tumor often present as solitary pulmonary nodule and excision biopsy can be curative. PMID:27977570

  8. Plasma. beta. -endorphin and stress hormone levels during adaptation and stress

    SciTech Connect

    Lishmanov, Yu.B.; Trifonova, Zh.V.; Tsibin, A.N.; Maslova, L.V.; Dement'eva, L.A.

    1987-09-01

    This paper describes a comparative study of ..beta..-endorphin and stress hormone levels in the blood plasma of rats during stress and adaptation. Immunoreactive ..beta..-endorphin in the blood plasma was assayed by means of a kit after preliminary isolation of the ..beta..-endorphin fraction by affinity chromatography on sepharose; ACTH was assayed with a kit and cortisol, insulin, thyroxine and tri-iodothyronine by means of kits from Izotop. Determination of plasma levels of ..beta..-endorphin and other opioids could evidently be an important method of assessing the state of resistance of the organism to stress.

  9. Comparison of 68Ga-DOTANOC PET/CT and contrast-enhanced CT in localisation of tumours in ectopic ACTH syndrome

    PubMed Central

    Jadhav, Swati S; Lila, Anurag R; Kasaliwal, Rajeev; Khare, Shruti; Yerawar, Chaitanya G; Hira, Priya; Phadke, Uday; Shah, Hina; Lele, Vikram R; Malhotra, Gaurav; Bandgar, Tushar; Shah, Nalini S

    2016-01-01

    Background Localising ectopic adrenocorticotrophic hormone (ACTH) syndrome (EAS) tumour source is challenging. Somatostatin receptor-based PET imaging has shown promising results, but the data is limited to case reports and small case series. We reviewed here the performance of 68Ga-DOTANOC positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) in our cohort of 12 consecutive EAS patients. Materials and methods Retrospective data analysis of 12 consecutive patients of EAS presenting to a single tertiary care centre in a period between January 2013 and December 2014 was done. CECT and 68Ga-DOTANOC PET/CT were reported (blinded) by an experienced radiologist and a nuclear medicine physician, respectively. The performance of CECT and 68Ga-DOTANOC PET/CT was compared. Results Tumours could be localised in 11 out of 12 patients at initial presentation (overt cases), whereas in one patient, tumour remained occult. Thirteen lesions were identified in 11 patients as EAS source (true positives). CECT localised 12 out of these 13 lesions (sensitivity 92.3%) and identified five false-positive lesions (positive predictive value (PPV) 70.5%). Compared with false-positive lesions, true-positive lesions had greater mean contrast enhancement at 60s (33.2 vs 5.6 Hounsfield units (HU)). 68Ga-DOTANOC PET/CT was able to identify 9 out of 13 lesions (sensitivity 69.2%) and reported no false-positive lesions (PPV 100%). Conclusion CECT remains the first-line investigation in localisation of EAS. The contrast enhancement pattern on CECT can further aid in characterisation of the lesions. 68Ga-DOTANOC PET/CT can be added to CECT, to enhance positive prediction of the suggestive lesions. PMID:27006371

  10. Validating the Novel Method of Measuring Cortisol Levels in Cetacean Skin by use of an ACTH Challenge in Bottlenose Dolphins

    DTIC Science & Technology

    2015-09-30

    in Cetacean Skin by use of an ACTH Challenge in Bottlenose Dolphins Thea Bechshoft Aarhus University Bioscience Roskilde Frederiksborgvej...using skin samples collected from bottlenose dolphins (Tursiops truncatus). The dolphins will be sampled as part of an ongoing out-of water stress test...N000141110436. The stress test in brief: Each dolphin is asked to perform a routine, voluntary beach into a padded beaching tray. Immediately following

  11. The Effects of Smoked Nicotine on Measures of Subjective states and Hypothalamic-Pituitary-Adrenal Axis Hormones in Women during the Follicular and Luteal Phases of the Menstrual Cycle

    PubMed Central

    Goletiani, Nathalie V.; Siegel, Arthur J.; Lukas, Scott E.; Hudson, James I.

    2015-01-01

    Objectives To determine the acute effects of cigarette smoking on hypothalamic-pituitary-adrenal axis (HPA) hormones and subjective states as a function of the menstrual cycle in nicotine-dependent women. Methods Seventeen healthy nicotine-dependent women were studied during the follicular and/or luteal phase of the menstrual cycle. Due to observation of a possible bimodal distribution of progesterone levels within the luteal phase group, we performed a set of a posteriori analyses. Therefore, we divided the luteal group into a low progesterone and a high progesterone groups. Results Smoked nicotine activated HPA, measured by ACTH, cortisol, and DHEA response and affected subjective states in both follicular and luteal phases, with increased “High”, “Rush”, and decreased “Craving”. The HPA stimulation revealed a blunting of ACTH response. There was only modest evidence for a blunting of subjective state responses in the luteal phase. However upon post hoc analyses, the high progesterone luteal group showed a marked blunting of measures of subjective states and a blunted ACTH response. Examining the association between hormone and measures of subjective states revealed tentative associations of ACTH stimulation with increased “Rush” and “Craving”, and DHEA stimulation with increased “Craving”. Conclusions This pilot study suggests that menstrual cycle phase differences in progesterone levels may attenuate nicotine’s addictive effects via diminution of its reinforcing properties, and augmentation of its aversive effects interfering with the pleasure associated with cigarette smoking. PMID:25783522

  12. [Hormonal dysnatremia].

    PubMed

    Karaca, P; Desailloud, R

    2013-10-01

    Because of antidiuretic hormone (ADH) disorder on production or function we can observe dysnatremia. In the absence of production by posterior pituitary, central diabetes insipidus (DI) occurs with hypernatremia. There are hereditary autosomal dominant, autosomal recessive or X- linked forms. When ADH is secreted but there is an alteration on his receptor AVPR2, it is a nephrogenic diabetes insipidus in acquired or hereditary form. We can make difference on AVP levels and/or on desmopressine response which is negative in nephrogenic forms. Hyponatremia occurs when there is an excess of ADH production: it is a euvolemic hypoosmolar hyponatremia. The most frequent etiology is SIADH (syndrome of inappropriate secretion of ADH), a diagnostic of exclusion which is made after eliminating corticotropin deficiency and hypothyroidism. In case of brain injury the differential diagnosis of cerebral salt wasting (CSW) syndrome has to be discussed, because its treatment is perfusion of isotonic saline whereas in SIADH, the treatment consists in administration of hypertonic saline if hyponatremia is acute and/or severe. If not, fluid restriction demeclocycline or vaptans (antagonists of V2 receptors) can be used in some European countries. Four types of SIADH exist; 10 % of cases represent not SIADH but SIAD (syndrome of inappropriate antidiuresis) due to a constitutive activation of vasopressin receptor that produces water excess. c 2013 Published by Elsevier Masson SAS.

  13. Role of neuronal and vascular Ca(2+)-channels in the ACTH-induced reversal of haemorrhagic shock.

    PubMed Central

    Guarini, S.; Bazzani, C.; Bertolini, A.

    1993-01-01

    1. In a rat model of volume-controlled haemorrhagic shock causing the death of all control (saline-treated) animals within 30 min, the intravenous (i.v.) bolus injection of ACTH-(1-24) at a dose of 160 micrograms kg-1 produced an impressive and sustained restoration of arterial pressure, pulse pressure and respiratory function, with 100% survival at the end of the observation period (2 h). 2. Both intracerebroventricular (i.c.v., 0.015-0.06 microgram kg-1) and i.v. (5 micrograms kg-1) pretreatment with the N-calcium channel blocker, omega-conotoxin GVIA, and i.v. (but not i.c.v.) pretreatment with the L-calcium channel blocker, nicardipine (125-500 micrograms kg-1) dose-dependently prevented the ACTH-induced shock reversal. 3. These results further indicate that the effect of ACTH in haemorrhagic shock may involve a neuronal link and the eventual restoration of vascular tone mediated by N- and L-type calcium channels, respectively. PMID:8395293

  14. Computed tomographic study of hormone-secreting microadenomas

    SciTech Connect

    Hemminghytt, S.; Kalkhoff, R.K.; Daniels, D.L.; Williams, A.L.; Grogan, J.P.; Haughton, V.M.

    1983-01-01

    A review was made of the computed tomographic (CT) studies of 33 patients with hormone-secreting microadenomas that had been verified by transsphenoidal surgery and endocrinologic evaluation. In previous studies in small series of patients, the CT appearance of pituitary microadenomas has been reported as hypodense, isodense, and hyperdense. In this study, CT showed a region of diminished enhancement and ususally an enlarged pituitary gland in cases of prolactin-secreting adenomas. HGH- or ACTH-secreting adenomas were less consistently hypodense. It is concluded that hypodensity and enlargement in the pituitary gland are the most useful criteria for identification of microadenomas. Some technical factors that may affect the CT appearance of microadenomas and lead to conflicting reports are discussed.

  15. Repetitive ultrasonographic assessment of adrenal size and shape changes: a clue for an asymptomatic sex hormone-secreting adenoma

    PubMed Central

    Yoon, Seunghyeon; Oui, Heejin; Lee, Ju-hwan; Son, Kyu-Yeol; Cho, Kyoung-Oh

    2017-01-01

    Diagnosis of an adrenal tumor without typical clinical signs related to hyperadrenocorticism and elevated alkaline phosphatase is challenging. This report describes a sex hormone-secreting adrenal tumor in a 10-year-old castrated male Shih Tzu evaluated through repetitive ultrasonographic examination. An adrenocorticotropic hormone stimulation test revealed elevated concentrations of androstenedione and 17-hydroxyprogesterone but a normal cortisol concentration. A mass was surgically excised and adenoma was diagnosed histopathologically. In the present case, adrenal tumor was strongly suspected based on a gradual increase in adrenal size and a change from peanut shape to an irregular mass on repetitive ultrasonography. Repetitive ultrasonographic examination of the adrenal gland is recommended when an abnormal ultrasonographic appearance of adrenal gland is identified, even in an asymptomatic dog. PMID:27297418

  16. Evaluation of adrenocortical function in Florida manatees (Trichechus manatus latirostris).

    PubMed

    Tripp, Kathleen M; Verstegen, John P; Deutsch, Charles J; Bonde, Robert K; de Wit, Martine; Manire, Charles A; Gaspard, Joseph; Harr, Kendal E

    2011-01-01

    The study objectives were to determine the predominant manatee glucocorticoid; validate assays to measure this glucocorticoid and adrenocorticotropic hormone (ACTH); determine diagnostic thresholds to distinguish physiological vs. pathological concentrations; identify differences associated with sex, age class, female reproductive status, capture time, and lactate; and determine the best methods for manatee biologists and clinicians to diagnose stress. Cortisol is the predominant manatee glucocorticoid. IMMULITE 1000 assays for cortisol and ACTH were validated. Precision yielded intra- and inter-assay coefficients of variation for serum cortisol: ≤23.5 and ≤16.7%; and ACTH: ≤6.9 and ≤8.5%. Accuracy resulted in a mean adjusted R(2)≥0.87 for serum cortisol and ≥0.96 for ACTH. Assay analytical sensitivities for cortisol (0.1 µg/dl) and ACTH (10.0 pg/ml) were verified. Methods were highly correlated with another IMMULITE 1000 for serum cortisol (r=0.97) and ACTH (r=0.98). There was no significant variation in cortisol or ACTH with sex or age class and no correlation with female progesterone concentrations. Cortisol concentrations were highest in unhealthy manatees, chronically stressed by disease or injury. ACTH was greatest in healthy free-ranging or short-term rehabilitating individuals, peracutely stressed by capture and handling. Cortisol concentrations ≥1.0 µg/dl were diagnostic of chronic stress; ACTH concentrations ≥87.5 pg/ml were diagnostic of peracute stress. In healthy long-term captive manatees, cortisol (0.4±0.2 µg/dl) and ACTH (47.7±15.9 pg/ml) concentrations were lower than healthy free-ranging, short-term rehabilitated or unhealthy manatees. Capture time was not significantly correlated with cortisol; ACTH correlation was borderline significant. Cortisol and ACTH were positively correlated with lactate.

  17. Evaluation of adrenocortical function in Florida manatees (Trichechus manatus latirostris)

    USGS Publications Warehouse

    Tripp, K.M.; Verstegen, J.P.; Deutsch, C.J.; Bonde, R.K.; Wit, M.D.; Manire, C.A.; Gaspard, J.; Harr, K.E.

    2011-01-01

    The study objectives were to determine the predominant manatee glucocorticoid; validate assays to measure this glucocorticoid and adrenocorticotropic hormone (ACTH); determine diagnostic thresholds to distinguish physiological vs. pathological concentrations; identify differences associated with sex, age class, female reproductive status, capture time, and lactate; and determine the best methods for manatee biologists and clinicians to diagnose stress. Cortisol is the predominant manatee glucocorticoid. IMMULITE 1000 assays for cortisol and ACTH were validated. Precision yielded intra- and inter-assay coefficients of variation for serum cortisol: ???23.5 and ???16.7%; and ACTH: ???6.9 and ???8.5%. Accuracy resulted in a mean adjusted R2???0.87 for serum cortisol and ???0.96 for ACTH. Assay analytical sensitivities for cortisol (0.1??g/dl) and ACTH (10.0pg/ml) were verified. Methods were highly correlated with another IMMULITE 1000 for serum cortisol (r=0.97) and ACTH (r=0.98). There was no significant variation in cortisol or ACTH with sex or age class and no correlation with female progesterone concentrations. Cortisol concentrations were highest in unhealthy manatees, chronically stressed by disease or injury. ACTH was greatest in healthy free-ranging or short-term rehabilitating individuals, peracutely stressed by capture and handling. Cortisol concentrations ???1.0??g/dl were diagnostic of chronic stress; ACTH concentrations ???87.5pg/ml were diagnostic of peracute stress. In healthy long-term captive manatees, cortisol (0.4??0.2??g/dl) and ACTH (47.7??15.9pg/ml) concentrations were lower than healthy free-ranging, short-term rehabilitated or unhealthy manatees. Capture time was not significantly correlated with cortisol; ACTH correlation was borderline significant. Cortisol and ACTH were positively correlated with lactate. ?? 2010 Wiley-Liss, Inc.

  18. Evaluation of adrenocortical function in Florida manatees (Trichechus manatus latirostris)

    USGS Publications Warehouse

    Tripp, K.M.; Verstegen, J.P.; Deutsch, C.; Bonde, Robert K.; de Wit, M.; Manire, C.A.; Gaspard, J.; Harr, K.E.

    2011-01-01

    The study objectives were to determine the predominant manatee glucocorticoid; validate assays to measure this glucocorticoid and adrenocorticotropic hormone (ACTH); determine diagnostic thresholds to distinguish physiological vs. pathological concentrations; identify differences associated with sex, age class, female reproductive status, capture time, and lactate; and determine the best methods for manatee biologists and clinicians to diagnose stress. Cortisol is the predominant manatee glucocorticoid. IMMULITE 1000 assays for cortisol and ACTH were validated. Precision yielded intra- and inter-assay coefficients of variation for serum cortisol: ≤23.5 and ≤16.7%; and ACTH: ≤6.9 and ≤8.5%. Accuracy resulted in a mean adjusted R(2)≥0.87 for serum cortisol and ≥0.96 for ACTH. Assay analytical sensitivities for cortisol (0.1 µg/dl) and ACTH (10.0 pg/ml) were verified. Methods were highly correlated with another IMMULITE 1000 for serum cortisol (r=0.97) and ACTH (r=0.98). There was no significant variation in cortisol or ACTH with sex or age class and no correlation with female progesterone concentrations. Cortisol concentrations were highest in unhealthy manatees, chronically stressed by disease or injury. ACTH was greatest in healthy free-ranging or short-term rehabilitating individuals, peracutely stressed by capture and handling. Cortisol concentrations ≥1.0 µg/dl were diagnostic of chronic stress; ACTH concentrations ≥87.5 pg/ml were diagnostic of peracute stress. In healthy long-term captive manatees, cortisol (0.4±0.2 µg/dl) and ACTH (47.7±15.9 pg/ml) concentrations were lower than healthy free-ranging, short-term rehabilitated or unhealthy manatees. Capture time was not significantly correlated with cortisol; ACTH correlation was borderline significant. Cortisol and ACTH were positively correlated with lactate.

  19. Diagnostic approach to Cushing disease.

    PubMed

    Gross, Bradley A; Mindea, Stefan A; Pick, Anthony J; Chandler, James P; Batjer, H Hunt

    2007-01-01

    In Cushing disease, a pituitary corticotroph neoplasm causes secondary adrenal hypercortisolism. This condition has known morbidity and mortality, underscoring the need for an efficient and accurate diagnostic approach. An 11 p.m. salivary cortisol level is a modern, simple initial screening tool for the diagnosis of Cushing syndrome. Confirmation with a 24-hour urinary free cortisol test and/or a low-dose dexamethasone suppression test may subsequently be performed. Patients with repeatedly equivocal results should be reevaluated after several months or undergo a corticotropin-releasing hormone (CRH) stimulation test following low-dose dexamethasone suppression to help rule out pseudo-Cushing states. The presence of low morning serum adrenocorticotropic hormone (ACTH) levels then distinguishes primary adrenal hypercortisolism from Cushing disease and the ectopic ACTH syndrome. Patients with moderate ACTH levels can undergo CRH stimulation testing to clarify the underlying disease because those with an ACTH-independent disorder have blunted subsequent ACTH levels. Once ACTH-dependent hypercortisolemia is detected, magnetic resonance (MR) imaging of the pituitary gland can be performed to detect a pituitary neoplasm. Normal or equivocal MR imaging results revealing small pituitary lesions should be followed up with inferior petrosal sinus sampling, a highly specific measure for the diagnosis of Cushing disease in experienced hands. If necessary, body imaging may be used in turn to detect sources of ectopic ACTH.

  20. Decreased GH secretion and enhanced ACTH and cortisol release after ghrelin administration in Cushing's disease: comparison with GH-releasing peptide-6 (GHRP-6) and GHRH.

    PubMed

    Correa-Silva, Silvia Regina; Nascif, Sérgio Oliva; Lengyel, Ana-Maria Judith

    2006-01-01

    GH responsiveness to GH secretagogues (GHS) is blunted in Cushing's disease (CD), while ACTH/cortisol responses are enhanced, by mechanisms still unclear. Ghrelin, the endogenous ligand for GHS-receptors (GHS-R), increases GH, ACTH, cortisol and glucose levels in humans. This study evaluated the GH, ACTH, cortisol and glucose-releasing effects of ghrelin in CD in comparison with GHRP-6. GHRH-induced GH release was also studied. Ten patients with CD (BMI 26.9+/-1.0 kg/m(2)) and ten controls (BMI 24.4+/-1.1 kg/m(2)) received ghrelin (1 microg/kg), GHRP-6 (1 microg/kg) and GHRH (100 microg) separately. GH, ACTH, cortisol and glucose levels were measured. In CD ghrelin-induced GH (microg/L; mean +/- SE) release (peak: 7.2+/-3.0) was higher than seen with GHRP-6 (2.7+/-1.0) and GHRH (0.7+/-0.2), but lower than in controls (ghrelin: 58.3+/-12.1; GHRP-6: 22.9+/-4.8; GHRH: 11.3+/-3.7). In controls ACTH (pg/mL) release after ghrelin (79.2+/-26.8) was higher than after GHRP-6 (23.6+/-5.7). In CD these responses (ghrelin: 192+/-43; GHRP-6: 185+/-56) were similar, and enhanced compared to controls. The same was observed with cortisol. Glucose levels failed to increase after ghrelin in CD, differently than in controls. Our data suggests that hypothalamic and pituitary pathways of GH release activated by ghrelin, GHRP-6 and GHRH are deranged in chronic hypercortisolism. The increased ACTH/cortisol responses to ghrelin and GHRP-6 in CD could be mediated by overexpression of GHS-R in ACTH-secreting adenomas. Hypercortisolism apparently impairs the ability of ghrelin to increase glucose levels.

  1. Electroencephalographic spreading depression and concomitant behavioral changes induced by intrahippocampal injections of ACTH1-24 and D-Ala2-Met-enkephalinamide in the rat.

    PubMed

    Oitzl, M S; Huston, J P

    1984-08-06

    ACTH1-24 (0.5 or 10 micrograms = 0.17 or 3.45 nmol) and D-Ala2-Met-enkephalinamide (DAME; 10 micrograms = 17.05 nmol) were injected unilaterally into the hippocampus of freely moving rats to examine their effects on EEG activity, DC potentials and behavior. In 85% of the rats DAME elicited spreading depression (SD) with epileptiform discharges preceding and following the wave of SD. The following behavioral changes were recorded. DAME- and KCl-induced SD were accompanied by an increase in locomotor activity and wet-dog shaking behavior, which occurred only during the period of SD. After a wave of SD induced by DAME a biphasic pattern of activity, consisting of an initial depression in locomotion followed by hyperactivity, appeared in 59% of the rats. ACTH1-24 elicited SD in 13% of the rats tested. Neither the dosage of ACTH1-24 nor the strain of rats influenced the occurrence of SD and the incidence of ACTH-induced grooming behavior. SD induced by KCl also resulted in excessive grooming comparable to that induced by ACTH1-24. In the case of KCl-induced SD, grooming began directly after the injection of KCl and was frequently interrupted by short periods of locomotion. ACTH-induced grooming had a later onset and episodes of stretching and yawning were observed. It can be concluded that the behavioral effects of the injection of DAME are unspecific responses to SD and seizure activity. However, ACTH-induced grooming is not solely a byproduct of SD, since it occurred also in the absence of SD.

  2. Adrenocortical steroid response to ACTH in different phenotypes of non-obese polycystic ovary syndrome

    PubMed Central

    2012-01-01

    Background Adrenal androgen excess is frequently observed in PCOS. The aim of the study was to determine whether adrenal gland function varies among PCOS phenotypes, women with hyperandrogenism (H) only and healthy women. Methods The study included 119 non-obese patients with PCOS (age: 22.2 ± 4.1y, BMI:22.5 ± 3.1 kg/m2), 24 women with H only and 39 age and BMI- matched controls. Among women with PCOS, 50 had H, oligo-anovulation (O), and polycystic ovaries (P) (PHO), 32 had O and H (OH), 23 had P and H (PH), and 14 had P and O (PO). Total testosterone (T), SHBG and DHEAS levels at basal and serum 17-hydroxprogesterone (17-OHP), androstenedione (A4), DHEA and cortisol levels after ACTH stimulation were measured. Results T, FAI and DHEAS, and basal and AUC values for 17-OHP and A4 were significantly and similarly higher in PCOS and H groups than controls (p < 0.05 for all) whereas three groups did not differ for basal or AUC values of DHEA and cortisol. Three hyperandrogenic subphenotypes (PHO, OH, and PH) compared to non-hyperandrogenic subphenotype (PO) had significantly and similarly higher T, FAI, DHEAS and AUC values for 17-OHP, A4 and DHEA (p < 0.05). All subphenotypes had similar basal and AUC values for cortisol. Conclusion PCOS patients and women with H only have similar and higher basal and stimulated adrenal androgen levels than controls. All three hyperandrogenic subphenotypes of PCOS exhibit similar and higher basal and stimulated adrenal androgen secretion patterns compared to non-hyperandrogenic subphenotype. PMID:23216997

  3. Effect of training on blood volume and plasma hormone concentrations in the elderly

    NASA Technical Reports Server (NTRS)

    Carroll, J. F.; Convertino, V. A.; Wood, C. E.; Graves, J. E.; Lowenthal, D. T.; Pollock, M. L.

    1995-01-01

    The purpose of this investigation was to determine the effects of 6 months of endurance training on resting plasma (PV) and blood volume (BV), and resting hormone and electrolyte concentrations in the elderly. Thirty-eight elderly men and women (ages 60-82 yr) were assigned to endurance exercise training (N = 29) or to control (N = 9) groups. Resting plasma levels of adrenocorticotropic hormone, vasopressin, aldosterone, norepinephrine, epinephrine, sodium, potassium, and protein were measured at the start (T1) and end (T2) of 26 wk of training. PV measurement was performed using the Evan's blue dye technique. Endurance training consisted of uphill treadmill walking or stairclimbing exercise 3 times.wk-1, 30-45 min.d-1, at 75-84% of maximal heart rate reserve. The exercise group increased VO2max by 11.2% (P < or = 0.05) and increased resting PV and BV by 11.2% and 12.7% (P < or = 0.05), respectively. Hormone and electrolyte levels in the exercise group remained unchanged; all variables were unchanged in the control group. These results are similar to findings in younger individuals. Because plasma hormone concentrations were maintained despite a chronically elevated BV, endurance training in healthy, elderly subjects may be associated with a resetting of volume receptors.

  4. Standardization of hormone determinations.

    PubMed

    Stenman, Ulf-Håkan

    2013-12-01

    Standardization of hormone determinations is important because it simplifies interpretation of results and facilitates the use of common reference values for different assays. Progress in standardization has been achieved through the introduction of more homogeneous hormone standards for peptide and protein hormones. However, many automated methods for determinations of steroid hormones do not provide satisfactory result. Isotope dilution-mass spectrometry (ID-MS) has been used to establish reference methods for steroid hormone determinations and is now increasingly used for routine determinations of steroids and other low molecular weight compounds. Reference methods for protein hormones based on MS are being developed and these promise to improve standardization.

  5. Hormonal effects in newborns

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001911.htm Hormonal effects in newborns To use the sharing features on this page, please enable JavaScript. Hormonal effects in newborns occur because in the womb babies ...

  6. Hormone Health Network

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... to hormones! Download our Free App! Understand the endocrine system and its related conditions with our 3D Patient ...

  7. Growth hormone deficiency

    MedlinePlus

    ... dosage of the medicine. Serious side effects of growth hormone treatment are rare. Common side effects include: Headache Fluid ... years. The rate of growth then slowly decreases. Growth hormone therapy does not work for all children. Left untreated, ...

  8. Hormones and Obesity

    MedlinePlus

    ... Balance › Hormones and Obesity Fact Sheet Hormones and Obesity March, 2010 Download PDFs English Espanol Editors Caroline Apovian, MD Judith Korner, MD, PhD What is obesity? Obesity is a chronic (long-term) medical problem ...

  9. Effect of blockade of postsynaptic H1 or H2 receptors or activation of presynaptic H3 receptors on catecholamine-induced stimulation of ACTH and prolactin secretion.

    PubMed

    Willems, E; Knigge, U; Jorgensen, H; Kjaer, A; Warberg, J

    2000-06-01

    The effect of inhibition of the neuronal histaminergic system by blockade of postsynaptic H1 or H2 receptors or activation of presynaptic H3 autoreceptors on the ACTH and prolactin responses to the catecholamines epinephrine and norepinephrine was investigated in conscious male rats. Intracerebroventricular infusion of epinephrine and norepinephrine stimulated ACTH and prolactin secretion. Prior intracerebroventricular infusion of the H1 receptor antagonist, mepyramine, or the H2 receptor antagonist, cimetidine, had no effect on the ACTH response to epinephrine or norepinephrine, while these responses were inhibited by pretreatment with the H3 receptor agonist, imetit. The prolactin response to norepinephrine was significantly inhibited by pretreatment with mepyramine, cimetidine or imetit whereas the three histaminergic compounds had no effect on the prolactin response to epinephrine. The findings suggest that the histaminergic system exerts a mediating or permissive action on the norepinephrine-induced stimulation of prolactin secretion, whereas an intact histaminergic system may not be required for catecholamines to stimulate ACTH secretion. The inhibitory effect of imetit on catecholamine-induced release of ACTH may be due to an activation of H3 receptors located presynaptically on non-histaminergic neurons, e.g. aminergic neurons. The study further indicates an important role of histamine in the neuroendocrine regulation of prolactin secretion.

  10. [Thyroid hormone resistance syndromes].

    PubMed

    Bernal, Juan

    2011-04-01

    Thyroid hormone resistance syndromes are a group of genetic conditions characterized by decreased tissue sensitivity to thyroid hormones. Three syndromes, in which resistance to hormone action is respectively due to mutations in the gene encoding for thyroid hormone receptor TRβ, impaired T4 and T3 transport, and impaired conversion of T4 to T3 mediated by deiodinases. An updated review of each of these forms of resistance is provided, and their pathogenetic mechanisms and clinical approaches are discussed.

  11. [Growth hormone treatment update].

    PubMed

    2014-02-01

    Short stature in children is a common cause for referral to pediatric endocrinologists, corresponding most times to normal variants of growth. Initially growth hormone therapy was circumscribed to children presenting growth hormone deficiency. Since the production of recombinant human hormone its use had spread to other pathologies.

  12. Lymphocytic hypophysitis in a dog with diabetes insipidus.

    PubMed

    Meij, B P; Voorhout, G; Gerritsen, R J; Grinwis, G C M; Ijzer, J

    2012-11-01

    An 8-year-old male German longhaired pointer was referred for diabetes insipidus responsive to treatment with desmopressin. The dog had polyuria and polydipsia, exercise intolerance and a dull hair coat. Plasma concentrations of thyroid-stimulating hormone, thyroxine, growth hormone (GH) and insulin-like growth factor-1 were decreased; plasma adrenocorticotropic hormone (ACTH) was slightly elevated and plasma α-melanocyte-stimulating hormone (MSH) was within the reference range. Computed tomography revealed a heterogeneously contrast-enhancing pituitary mass compressing the hypothalamus. Transsphenoidal hypophysectomy was performed and microscopical examination of the surgical biopsy samples revealed hypophysitis without evidence of pituitary adenoma. The hypophysitis was characterized by marked lymphocytic infiltration of the adenohypophysis that contained a mixed population of neuroendocrine cells expressing GH, ACTH or α-MSH. The lymphocytes were identified as T cells, resulting in a final diagnosis of lymphocytic hypophysitis strongly resembling human primary lymphocytic hypophysitis.

  13. Evidence-based guideline update: Medical treatment of infantile spasms

    PubMed Central

    Go, C.Y.; Mackay, M.T.; Weiss, S.K.; Stephens, D.; Adams-Webber, T.; Ashwal, S.; Snead, O.C.

    2012-01-01

    Objective: To update the 2004 American Academy of Neurology/Child Neurology Society practice parameter on treatment of infantile spasms in children. Methods: MEDLINE and EMBASE were searched from 2002 to 2011 and searches of reference lists of retrieved articles were performed. Sixty-eight articles were selected for detailed review; 26 were included in the analysis. Recommendations were based on a 4-tiered classification scheme combining pre-2002 evidence and more recent evidence. Results: There is insufficient evidence to determine whether other forms of corticosteroids are as effective as adrenocorticotropic hormone (ACTH) for short-term treatment of infantile spasms. However, low-dose ACTH is probably as effective as high-dose ACTH. ACTH is more effective than vigabatrin (VGB) for short-term treatment of children with infantile spasms (excluding those with tuberous sclerosis complex). There is insufficient evidence to show that other agents and combination therapy are effective for short-term treatment of infantile spasms. Short lag time to treatment leads to better long-term developmental outcome. Successful short-term treatment of cryptogenic infantile spasms with ACTH or prednisolone leads to better long-term developmental outcome than treatment with VGB. Recommendations: Low-dose ACTH should be considered for treatment of infantile spasms. ACTH or VGB may be useful for short-term treatment of infantile spasms, with ACTH considered preferentially over VGB. Hormonal therapy (ACTH or prednisolone) may be considered for use in preference to VGB in infants with cryptogenic infantile spasms, to possibly improve developmental outcome. A shorter lag time to treatment of infantile spasms with either hormonal therapy or VGB possibly improves long-term developmental outcomes. PMID:22689735

  14. The effects of palm vitamin E on stress hormone levels and gastric lesions in stress-induced rats

    PubMed Central

    Aziz Ibrahim, Ibrahim Abdel; Kamisah, Yusof; Nafeeza, Mohd Ismail

    2012-01-01

    Introduction This study examines the effects of palm vitamin E (PVE) or α-tocopherol (α-TF) supplementation on adrenocorticotropin hormone (ACTH), corticosterone and gastric lesions in rats exposed to water-immersion restraint stress (WIRS). Material and methods Sixty male Sprague-Dawley rats (200-250 g) were divided into three groups. Group I: 20 rats as a control group were given a normal diet. Group II: 20 rats received oral supplementation of PVE at 60 mg/kg body weight. Group III: 20 rats received oral supplementation of α-TF at 60 mg/kg body weight. After the treatment period of 28 days, each group was further subdivided into two groups: 10 rats not exposed to stress, and the other 10 rats subjected to WIRS for 3.5 h. Blood samples were taken to measure the ACTH and corticosterone levels. The rats were then sacrificed and the stomach excised and opened along the greater curvature and examined for lesions. Results Rats exposed to WIRS had lesions in their stomach mucosa. Our findings showed that dietary supplementation of PVE or α-TF was able to reduce gastric lesions significantly in comparison to the stressed controls. The WIRS increased plasma ACTH and corticosterone significantly. Palm vitamin E and α-TF treatments reduced these parameters significantly compared to the stressed controls. Conclusions Supplementation with either PVE or α-TF reduces the formation of gastric lesions, probably by inhibiting the elevation of ACTH and corticosterone levels induced by stress. PMID:22457670

  15. Hypothermic and antipyretic effects of ACTH (1-24) and alpha-melanotropin in guinea-pigs

    NASA Technical Reports Server (NTRS)

    Kandasamy, S. B.; Williams, B. A.

    1984-01-01

    Intracerebroventricular administration of adrenocorticotropin (ACTH 1-24) and alpha-melanotropin (alpha-MSH), peptides which occur naturally in brain induced dose-related hypothermia in guinea-pigs at room temperature (21 C) and also produced greater hypothermia at low (10 C) ambient temperature. However, when the experiments were repeated in a warm (30 C) environment, no effect on body temperature was observed. These results indicate that the peptides did not reduce the central set-point of temperature control. The hypothermia induced by ACTH and alpha-MSH was not mediated via histamine H1- or H2-receptors and serotonin since the H1-receptor antagonist, mepyramine, the H2-receptor antagonist, cimetidine, and the serotonin antagonist, methysergide, had no antagonistic effects. The peptides were antipyretic since they reduced pyrogen-induced-fever and hyperthermia due to prostaglandin E2, norepinephrine and dibutyryl cAMP, at a dose which did not affect normal body temperature. The powerful central effects of these peptides on normal body temperature, fever and hyperthermia, together with their presence of the brain regions important to temperature control, suggest that they participate in thermoregulation.

  16. Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis

    PubMed Central

    Wang, Renzhi; Yang, Yakun; Sheng, Miaomiao; Bu, Dechao; Huang, Fengming; Liu, Xiaohai; Zhou, Cuiqi; Dai, Congxin; Sun, Bowen; Zhu, Jindong; Qiao, Yi; Yao, Yong; Zhu, Huijuan; Lu, Lin; Pan, Hui; Feng, Ming; Deng, Kan; Xing, Bing; Lian, Wei; Zhao, Yi; Jiang, Chengyu

    2016-01-01

    Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT). We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1), collagen type I α 1 chain (COL1A1), 5′-nucleotidase ecto (NT5E), HtrA serine peptidase 1 (HTRA1) and angiopoietin 1 (ANGPT1) and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment. PMID:27690016

  17. Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties.

    PubMed

    Magrì, Antonio; Tabbì, Giovanni; Giuffrida, Alessandro; Pappalardo, Giuseppe; Satriano, Cristina; Naletova, Irina; Nicoletti, Vincenzo G; Attanasio, Francesco

    2016-11-01

    Semax is a heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) that encompasses the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone and a C-terminal Pro-Gly-Pro tripeptide. N-terminal amino group acetylation (Ac-Semax) modulates the chemical and biological properties of parental peptide, modifying the ability of Semax to form complex species with Cu(II) ion. At physiological pH, the main complex species formed by Ac-Semax, [CuLH-2](2-), consists in a distorted CuN3O chromophore with a weak apical interaction of the methionine sulphur. Such a complex differs from the Cu(II)-Semax complex system, which exhibits a CuN4 chromophore. The reduced ligand field affects the [CuLH-2](2-) formal redox potential, which is more positive than that of Cu(II)-Semax corresponding species. In the amino-free form, the resulting complex species is redox-stable and unreactive against ascorbic acid, unlike the acetylated form. Semax acetylation did not protect from Cu(II) induced toxicity on a SH-SY5Y neuroblastoma cell line, thus demonstrating the crucial role played by the free NH2 terminus in the cell protection. Since several brain diseases are associated either to Cu(II) or Zn(II) dyshomeostasis, here we characterized also the complex species formed by Zn(II) with Semax and Ac-Semax. Both peptides were able to form Zn(II) complex species with comparable strength. Confocal microscopy imaging confirmed that peptide group acetylation does not affect the Zn(II) influx in neuroblastoma cells. Moreover, a punctuate distribution of Zn(II) within the cells suggests a preferred subcellular localization that might explain the zinc toxic effect. A future perspective can be the use of Ac-Semax as ionophore in antibody drug conjugates to produce a dysmetallostasis in tumor cells.

  18. Comparative endocrinological responses to short transportation of Equidae (Equus asinus and Equus caballus).

    PubMed

    Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Aveni, Francesca; Ferlazzo, Adriana

    2013-03-01

    In order to evaluate the effects of short transportation on β-endorphin, adrenocorticotropic hormone (ACTH) and cortisol changes, 12 healthy stallions of Equidae (Equus asinus and Equus caballus) were studied before and after transportation of 50 km. Blood samples were collected 1 week before transportation in basal conditions, immediately before loading and after transportation and unloading, on their arrival at the breeding station. Compared to basal and before values, donkeys showed an increase in circulating ACTH (P < 0.001) and cortisol (P < 0.0005) levels after transportation and higher ACTH (P < 0.01) levels than horses after transportation. A positive and significant correlation (r = 0.885; P < 0.01) between ACTH and cortisol levels after transportation was found. No significant differences were observed for β-endorphin levels. Compared to basal and before values, horses showed higher cortisol (P < 0.005) levels after transportation and no significant differences were observed for ACTH and β-endorphin levels in donkeys. Horses facing forward (direction of travel) showed higher (P < 0.01) β-endorphin levels after transportation than donkeys; horses facing backward (the opposite direction of travel) showed lower (P < 0.05) ACTH levels after transportation. The results indicate that short transportation induces a preferential activation of the hypothalamus-pituitary-axis (HPA), with significant release of ACTH and cortisol in donkeys and only of cortisol in horses, suggesting that transportation for donkeys may be more stressful than horses.

  19. Hormonal responses to acute exercise, training and overtraining. A review with emphasis on the horse.

    PubMed

    de Graaf-Roelfsema, E; Keizer, H A; van Breda, E; Wijnberg, I D; van der Kolk, J H

    2007-09-01

    Overtraining is an imbalance between training and recovery leading to symptoms associated with a neuroendocrine dysbalance called the overtraining syndrome, a disease characterized by behavioral, emotional and physical symptoms similar with depression. Although the prevalence of overtraining is high in human and equine athletes, at present no sensitive and specific test is available to prevent or diagnose overtraining. Nowadays, it is believed that combination of different (hormonal) parameters appear to be the best indicators of overtraining. Therefore, this review provides a summary of previous literature examining the response of the hypothalamic-pituitary-adrenal (HPA) axis and the growth hormone-insulin-like growth factor-I (GH-IGF-I) axis to acute and chronic exercise as well as overtraining in humans and horses. The exercise induced hormonal responses seem to be equal for the equine as well as the human athlete, which makes comparisons possible. Repeated bouts of exercise are suggested to provide a way to detect subtle changes in hormonal responses in the individual athlete, which may make them an important tool in detecting early overtraining. This should be combined with corticotropin releasing hormone (CRH) stimulation tests and basal ACTH and GH pulsatility determination. Further research is needed to establish the correct training intensity and rest period for the exercise test in equines.

  20. Influence of adrenocorticotrophin hormone challenge and external factors (age, sex, and body region) on hair cortisol concentration in Canada lynx (Lynx canadensis).

    PubMed

    Terwissen, C V; Mastromonaco, G F; Murray, D L

    2013-12-01

    Land use changes are a significant factor influencing the decline of felid populations. However, additional research is needed to better understand how these factors influence populations in the wild. Hormone analysis can provide valuable information on the basic physiology and overall health of an animal, and enzyme immunoassays (EIA) are generally used for hair hormone analysis but must first be validated for the substrate of choice and species of interest. To date, hormone assays from hair have not been validated for Felidae, despite that the method holds considerable promise for non-invasive sampling of free-ranging animals. We sought to: (1) evaluate whether increased adrenocorticotrophin hormone (ACTH) during the period of hair growth results in elevated hair cortisol; (2) validate the enzyme immunoassay used; and (3) identify any variations in hair cortisol between age, sex and body regions, using Canada lynx. We quantified hair cortisol concentrations in captive animals through an ACTH challenge and collected samples from legally harvested lynx to compare variability between body regions. An EIA was validated for the analysis of hair cortisol. Lynx (n=3) had a qualitative increase in hair cortisol concentration following an ACTH challenge in captive animals (20 IU/kg of body weight weekly for 5 weeks), thereby supporting the use of an EIA to quantify cortisol values in hair. Based on our analysis of sampled lynx pelts, we found that hair cortisol did not vary between age and sex, but varied within the foot/leg region to a greater extent than between individuals. We recommend that future studies identify a standardized location for hair cortisol sampling.

  1. Stokes radius determination of radioiodinated polypeptide hormones by gel filtration

    SciTech Connect

    Ribela, M.T.; Bartolini, P.

    1988-11-01

    A simple technique for determination of the molecular (Stokes) radius of radioiodinated proteins was developed using the same column and chromatographic conditions employed in routine radioimmunoassay tracer purification. The calibration curve for five radioiodinated standard proteins presented a highly significant correlation (r = -0.996; P less than 0.001) and allowed precise molecular radius determination for labeled human growth hormone (hGH), luteotropin (hLH), follicle-stimulating hormone (hFSH), thyrotropin (hTSH), prolactin (hPRL), and corticotropin (hACTH), enabling detection of differences of the order of +/- 3%. The validity of the method was verified by determining the molecular radius of hGH in both ''cold'' (unlabeled standards and unknowns) and ''hot'' (radioiodinated standards and unknowns) systems. The technique can be applied in a very simple manner, requiring just one simple additional calibration run before Sephadex G-100 tracer purification. Furthermore, it can be applied to any protein, even when only extremely limited amounts are available. Since the standards and unknowns are labeled and chromatographed under identical conditions, potential common alterations of the molecule due to oxidation, iodine incorporation, tracer-carrier interactions, etc., are automatically corrected for.

  2. Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test

    PubMed Central

    Rodríguez-Gutiérrez, René; Rendon, Adrian; Barrera-Sánchez, Maximiliano; Carlos-Reyna, Kevin Erick Gabriel; Álvarez-Villalobos, Neri Alejandro; González-Saldivar, Gloria; González-González, José Gerardo

    2016-01-01

    Background. Multidrug-resistant tuberculosis (MDR-TB) is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction) that if not diagnosed could seriously jeopardize patients' health. Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 μg) ACTH stimulation test at baseline and at 6–12 months of follow-up after antituberculosis treatment and culture conversion. Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB) were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 μg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment. Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2%) of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3%) alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2 ± 3.6 months) adrenocortical function was restored in all cases. Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical dysfunction or

  3. Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test.

    PubMed

    Rodríguez-Gutiérrez, René; Rendon, Adrian; Barrera-Sánchez, Maximiliano; Carlos-Reyna, Kevin Erick Gabriel; Álvarez-Villalobos, Neri Alejandro; González-Saldivar, Gloria; González-González, José Gerardo

    2016-01-01

    Background. Multidrug-resistant tuberculosis (MDR-TB) is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction) that if not diagnosed could seriously jeopardize patients' health. Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 μg) ACTH stimulation test at baseline and at 6-12 months of follow-up after antituberculosis treatment and culture conversion. Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB) were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 μg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment. Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2%) of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3%) alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2 ± 3.6 months) adrenocortical function was restored in all cases. Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical dysfunction or treat

  4. Hormones and Cancer

    PubMed Central

    Blackstein, Martin Elliot

    1984-01-01

    Hormonal therapy is the first systemic therapy to have been used successfully in the treatment of cancer. Developments in steroid hormone receptor assays in the last decade have resulted in the first predictable assays for cancer therapy. The role of hormones, in both the development and treatment of breast, prostate and uterine cancer, is reviewed. Because hormonal therapy is generally a less toxic palliative treatment than other treatments (e.g., chemotherapy and radiation), it has been used for malignancies such as malignant melanoma, hypernephroma, and carcinoid. PMID:21278945

  5. Seasonal changes in the cytomorphology of hypophyseal ACTH cells in relation to the reproduction cycle of the female of the frog Rana tigerina (Daud.).

    PubMed

    Pramoda, S; Saidapur, S K

    1991-01-01

    The hypophyseal ACTH (basophil type 3 or B3), cells of R. tigerina display seasonal changes in cytomorphology (nuclear, cytoplasm and cell area), staining intensity and cytoplasmic granulation. The cytoplasmic granules are fine and stain blackish purple with McConaill's lead haematoxylin, with Herlant's AB and the PAS and OG techniques they stain brownish red. The tinctorial response of their cytoplasm is PAS- and OG-positive and AB-negative. The B3 cells are low columnar or cuboidal in form and are smaller than the gonadotrophs (B2 cells). Towards the rostral border of the pars distalis they are larger and are associated with blood vessels, whereas in the caudal region they are smaller. Seasonal changes in the granulation and degranulation of the ACTH cells are also more prominent in the rostral region of the pars distalis than in the caudal region. During April, May and June a marked increase occurs in ACTH cell size and the number of cytoplasmic secretory granules, concurrently with events like vitellogenesis, lipid depletion from the fat bodies and breeding activity. During the post-breeding regression phase (and especially from August to November), the B3 cells decrease markedly in size and become devoid of secretory granules; their recovery begins slowly from December onwards. The findings suggest that the secretory activity of the ACTH cells in the frog undergoes seasonal changes which possibly influence vitellogenesis, lipolysis of the fat bodies and breeding activity.

  6. Further evidence for ancient role of ACTH peptides at melanocortin (MC) receptors; pharmacology of dogfish and lamprey peptides at dogfish MC receptors.

    PubMed

    Haitina, Tatjana; Takahashi, Akiyoshi; Holmén, Linnea; Enberg, Johan; Schiöth, Helgi B

    2007-04-01

    The cloning of melanocortin (MC) receptors in distant species has provided us tools to get insight in how the ligand-receptors interactions in the MC system have evolved. We have however lacked studies on pharmacology of native ancient melanocortin peptides at the ancient MC receptors. In this paper we synthesized melanocortin peptides from both the sea lamprey (Petromyzon marinus) and spiny dogfish (Squalus acanthias) and tested them on the MC3 and MC4 receptors from spiny dogfish. The results show that both the dogfish and lamprey ACTH peptides have similar or higher affinity than the dogfish alpha-, beta- and gamma-MSH peptides to the dogfish MC3 and MC4 receptors. Moreover, both the dogfish and lamprey ACTH peptides have more than 10-fold higher affinity than alpha-MSH to the dogfish MC4 receptor. We also show that dogfish delta-MSH is able to bind to MC receptors and its potency is higher than of dogfish beta-MSH, which is considered to be its precursor. Our results provide the first evidence that native ACTH ligands from dogfish and lamprey have a preference above native MSH peptides to ancient version of the MC3 and MC4 receptors. This further strengthens the hypotheses that the ligand contributing to the first version of the melanocortin ligand-receptor system resembled ACTH.

  7. [Glutamate neurotransmission, stress and hormone secretion].

    PubMed

    Jezová, D; Juránková, E; Vigas, M

    1995-11-01

    Glutamate neurotransmission has been investigated in relation to several physiological processes (learning, memory) as well as to neurodegenerative and other disorders. Little attention has been paid to its involvement in neuroendocrine response during stress. Penetration of excitatory amino acids from blood to the brain is limited by the blood-brain barrier. As a consequence, several toxic effects but also bioavailability for therapeutic purposes are reduced. A free access to circulating glutamate is possible only in brain structures lacking the blood-brain barrier or under conditions of its increased permeability. Excitatory amino acids were shown to stimulate the pituitary hormone release, though the mechanism of their action is still not fully understood. Stress exposure in experimental animals induced specific changes in mRNA levels coding the glutamate receptor subunits in the hippocampus and hypothalamus. The results obtained with the use of glutamate receptor antagonists indicate that a number of specific receptor subtypes contribute to the stimulation of ACTH release during stress. The authors provided also data on the role of NMDA receptors in the control of catecholamine release, particularly in stress-induced secretion of epinephrine. These results were the first piece of evidence on the involvement of endogenous excitatory amino acids in neuroendocrine activation during stress. Neurotoxic effects of glutamate in animals are well described, especially after its administration in the neonatal period. In men, glutamate toxicity and its use as a food additive are a continuous subject of discussions. The authors found an increase in plasma cortisol and norepinephrine, but not epinephrine and prolactin, in response to the administration of a high dose of glutamate. It cannot be excluded that these effects might be induced even by lower doses in situations with increased vulnerability to glutamate action (age, individual variability). (Tab. 1, Fig. 6, Ref. 44.).

  8. Adrenal venous sampling in a patient with adrenal Cushing syndrome

    PubMed Central

    Villa-Franco, Carlos Andrés; Román-Gonzalez, Alejandro; Velez-Hoyos, Alejandro; Echeverri-Isaza, Santiago

    2015-01-01

    The primary bilateral macronodular adrenal hyperplasia or the independent adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause hypercortisolism, its diagnosis is challenging and there is no clear way to decide the best therapeutic approach. Adrenal venous sampling is commonly used to distinguish the source of hormonal production in patients with primary hyperaldosteronism. It could be a useful tool in this context because it might provide information to guide the treatment. We report the case of a patient with ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with some modifications radically modified the treatment and allowed the diagnosis of a macronodular adrenal hyperplasia. PMID:26309345

  9. Adrenal venous sampling in a patient with adrenal Cushing syndrome.

    PubMed

    Builes-Montaño, Carlos Esteban; Villa-Franco, Carlos Andrés; Román-Gonzalez, Alejandro; Velez-Hoyos, Alejandro; Echeverri-Isaza, Santiago

    2015-01-01

    The primary bilateral macronodular adrenal hyperplasia or the independent adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause hypercortisolism, its diagnosis is challenging and there is no clear way to decide the best therapeutic approach. Adrenal venous sampling is commonly used to distinguish the source of hormonal production in patients with primary hyperaldosteronism. It could be a useful tool in this context because it might provide information to guide the treatment. We report the case of a patient with ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with some modifications radically modified the treatment and allowed the diagnosis of a macronodular adrenal hyperplasia.

  10. Immunocytochemical evidence for the presence of gamma 1-MSH-like immunoreactivity in pituitary corticotrophs and ACTH-producing tumours.

    PubMed

    Ali-Rachedi, A; Ferri, G L; Varndell, I M; Van Noorden, S; Schot, L P; Ling, N; Bloom, S R; Polak, J M

    1983-12-01

    The presence of gamma 1-MSH has been demonstrated in bovine neuro-intermediate lobe by biochemical methods, thus suggesting that this peptide is cleaved from the cryptic region of pro-opiocortin. In this study we report the localisation of gamma 1-MSH-like immunoreactivity in the adenohypophysis of man, ox, pig, dog and guinea-pig using immunocytochemical procedures at both light and electron microscope levels. Antisera recognising the C-terminal Arg-Phe-amide and the C-terminal penta-peptide-amide of gamma 1-MSH have been used throughout this study. The immunostaining was found in all endocrine cells of the pars intermedia (where present) and in scattered cells of the pars distalis identified as corticotrophs. No gamma 1-MSH immunoreactivity was detected in rat adenohypophysis. In addition, 7 ACTH-producing tumours (1 pituitary adenoma and 6 ectopic) were investigated and shown to contain gamma 1-MSH immunoreactive cells.

  11. The Value of Somatostatin Receptor Imaging with In-111 Octreotide and/or Ga-68 DOTATATE in Localizing Ectopic ACTH Producing Tumors

    PubMed Central

    Gözde Özkan, Zeynep; Kuyumcu, Serkan; Balköse, Deniz; Özkan, Berker; Aksakal, Nihat; Yılmaz, Ebru; Şanlı, Yasemin; Türkmen, Cüneyt; Aral, Ferihan; Adalet, Işık

    2013-01-01

    Objective: We aimed to evaluate the value of somatostatin receptor imaging (SRI) with In-111 octreotide and Ga-68 DOTATATE in localizing ectopic ACTH producing tumors. Methods: Nineteen patients who had In-111 octreotide somatostatin receptor scintigraphy (SRS) and/or Ga-68 DOTATATE PET-CT to localize ectopic ACTH producing tumors between the years 2000 and 2012 were included retrospectively in our study. The results of SRI were compared with clinical onset, radiological findings and surgical data of the patients. Results: Sixteen In-111 octreotide SRS and five Ga-68 DOTATATE PET-CT were performed in 19 patients. In eight out of 19 patients, ectopic ACTH secretion site could be detected. In five patients, SRS showed pathologic uptake. In four of these patients, surgery revealed pulmonary carcinoid tumors and in one patient pancreatic neuroendocrine tumor. In one patient, Ga-68 DOTATATE PET-CT revealed pathologic uptake in lung nodule which came out to be pulmonary carcinoid tumor. In another patient who had resection of metastases of atypi