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  1. ACTH stimulation test

    Science.gov (United States)

    ... Groot LJ, de Kretser DM, et al, eds. Endocrinology: Adult and Pediatric . 7th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 102. Chernecky CC, Berger BJ. ACTH stimulation test - diagnostic. In: ... . 13th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ...

  2. ACTH blood test

    Science.gov (United States)

    ... gland not producing enough hormones, such as ACTH ( hypopituitarism ) Tumor of the adrenal gland that produces too ... syndrome due to adrenal tumor Ectopic Cushing syndrome Hypopituitarism Multiple endocrine neoplasia (MEN) I Review Date 10/ ...

  3. The expression of the ACTH receptor

    Directory of Open Access Journals (Sweden)

    L.L.K. Elias

    2000-10-01

    Full Text Available Adrenal glucocorticoid secretion is regulated by adrenocorticotropic hormone (ACTH acting through a specific cell membrane receptor (ACTH-R. The ACTH-R is a member of the G protein superfamily-coupled receptors and belongs to the subfamily of melanocortin receptors. The ACTH-R is mainly expressed in the adrenocortical cells showing a restricted tissue specificity, although ACTH is recognized by the other four melanocortin receptors. The cloning of the ACTH-R was followed by the study of this gene in human diseases such as familial glucocorticoid deficiency (FGD and adrenocortical tumors. FGD is a rare autosomal recessive disease characterized by glucocorticoid deficiency, elevated plasma ACTH levels and preserved renin/aldosterone secretion. This disorder has been ascribed to an impaired adrenal responsiveness to ACTH due to a defective ACTH-R, a defect in intracellular signal transduction or an abnormality in adrenal cortical development. Mutations of the ACTH-R have been described in patients with FGD in segregation with the disease. The functional characterization of these mutations has been prevented by difficulties in expressing human ACTH-R in cells that lack endogenous melanocortin receptor activity. To overcome these difficulties we used Y6 cells, a mutant variant of the Y1 cell line, which possesses a non-expressed ACTH-R gene allowing the functional study without any background activity. Our results demonstrated that the several mutations of the ACTH-R found in FGD result in an impaired cAMP response or loss of sensitivity to ACTH stimulation. An ACTH-binding study showed an impairment of ligand binding with loss of the high affinity site in most of the mutations studied.

  4. EDTA interference in electrochemiluminescence ACTH assay.

    Science.gov (United States)

    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.

  5. The effect of ACTH on suckling rats.

    Science.gov (United States)

    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.

  6. Proliferative signaling initiated in ACTH receptors

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    C.F.P. Lotfi

    2000-10-01

    Full Text Available This article reviews recent results of studies aiming to elucidate modes of integrating signals initiated in ACTH receptors and FGF2 receptors, within the network system of signal transduction found in Y1 adrenocortical cells. These modes of signal integration should be central to the mechanisms underlying the regulation of the G0->G1->S transition in the adrenal cell cycle. FGF2 elicits a strong mitogenic response in G0/G1-arrested Y1 adrenocortical cells, that includes a rapid and transient activation of extracellular signal-regulated kinases-mitogen-activated protein kinases (ERK-MAPK (2 to 10 min, b transcription activation of c-fos, c-jun and c-myc genes (10 to 30 min, c induction of c-Fos and c-Myc proteins by 1 h and cyclin D1 protein by 5 h, and d onset of DNA synthesis stimulation within 8 h. ACTH, itself a weak mitogen, interacts with FGF2 in a complex manner, blocking the FGF2 mitogenic response during the early and middle G1 phase, keeping ERK-MAPK activation and c-Fos and cyclin D1 induction at maximal levels, but post-transcriptionally inhibiting c-Myc expression. c-Fos and c-Jun proteins are mediators in both the strong and the weak mitogenic responses respectively triggered by FGF2 and ACTH. Induction of c-Fos and stimulation of DNA synthesis by ACTH are independent of PKA and are inhibited by the PKC inhibitor GF109203X. In addition, ACTH is a poor activator of ERK-MAPK, but c-Fos induction and DNA synthesis stimulation by ACTH are strongly inhibited by the inhibitor of MEK1 PD98059.

  7. Adrenocorticotrophic hormone (ACTH) stimulation of sheep fetal adrenal cortex can occur without increased expression of ACTH receptor (ACTH-R) mRNA

    DEFF Research Database (Denmark)

    Carter, A M; Petersen, Y M; Towstoless, M;

    2002-01-01

    In the present study, it was hypothesized that the adrenocorticotrophin hormone receptor (ACTH-R) would be up-regulated in the adrenal gland of the sheep fetus following infusion of physiological amounts of ACTH, as shown for adrenal cortical cells in culture. In chronically catheterized sheep, a...

  8. ACTH overexpressing pituitary hyperplasia in a patient with ectopic ACTH-syndrome due to carcinoid of the lung

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    Larisa Konstantinovna Dzeranova

    2015-01-01

    Full Text Available Ectopic ACTH-syndrome is the most diagnostically challenging  variant of endogenous hypercortisolism. Particularly difficult differential diagnosis of this syndrome is from Cushing's disease (CD, as currently there is no single test sufficiently accurate to differentiate accurately ectopic ACTH production from the pituitary. The main functional tests are based on the fact that the vast majority of ectopic ACTH production is autonomous and suppresses one from pituitary. But in some cases this is not observed, and then the data obtained all necessary laboratory and instrumental research evidence in favor of central genesis of CD in a patient with ACTH ectopic secretion, which can lead to inappropriate treatment. If you confirm the ectopic ACTH-syndrome, it may take quite a long time of searching for the pathological focus, as there is no sufficiently precise imaging and diagnostic method for determining the localization of ectopic source of ACTH production. Thus, the differential diagnosis of ACTH-dependent hypercortisolism and localization of the ectopic tumor is the cornerstone of early and radical treatment of patients. We present a difficult clinical case of a patient having a pituitary hyperplasia with excessive ACTH expression with primary ectopic ACTH syndrome caused by lung carcinoid.

  9. Comparisons of synthetic 1-18 ACTH (Organon 2001) and 1-39 ACTH of animal origin in human subjects.

    Science.gov (United States)

    Danowski, T S; Fisher, E R; Robinson, S M

    The studies in human subjects herein reported provide data on the relative effects of 1-18 ACTH (Organon 2001) and commercial 1-39 ACTH of animal origin on plasma cortisol, serum non-esterified fatty acids, and certain urinary steroids.

  10. ACTH stimulation test in the captive cheetah (Acinonyx jubatus

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    L.S. Koster

    2007-06-01

    Full Text Available Serum cortisol response was assessed in 8 captive cheetahs, of varying ages, after the intravenous administration of 500 µg of tetracosactide (Synacthen Depot(R, 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.

  11. ACTH-secreting bronchial carcinoid: a diagnostic and therapeutic challenge.

    LENUS (Irish Health Repository)

    McDermott, J H

    2008-09-01

    We describe a case of Cushing\\'s syndrome due to ectopic ACTH secretion, where the only potential source on conventional imaging was a tiny benign-appearing lung nodule, which failed to take up radiolabelled octreotide.

  12. Direct actions of ACTH on ovarian function of pseudopregnant rabbits

    OpenAIRE

    Guelfi, Gabriella; Zerani, Massimo; Brecchia, Gabriele; Parillo, Francesco; Dall'Aglio, Cecilia; Maranesi, Margherita; Boiti, Cristiano

    2011-01-01

    Abstract The present study sought to assess whether the receptors for adrenocorticotropic hormone (ACTH), MC2R, and for glucocorticoid (GR) are expressed in corpora lutea (CL) of pseudopregnant rabbits and whether ACTH and cortisol exert any direct action on luteal function. By immunohistochemistry, positive reaction for MC2R and GR was detectable within luteal cells of CL. The MC2R mRNA levels were five-fold less abundant in day 9 than in day 4 CL (P , Italy.--> ...

  13. ACTH Action on Messenger RNA Stability Mechanisms

    Science.gov (United States)

    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.

  14. Structure-activity studies with ACTH/α-MSH fragments on corticosteroid secretion of isolated zona glomerulosa and fasciculata cells

    NARCIS (Netherlands)

    Szalay, Katalin Sz.; Wied, D. De; Stark, E.; Folly, G.

    1985-01-01

    The steroidogenic action of ACTH/α-MSH fragments was studied on isolated zona glomerulosa and zona fasciculata cells dispersed by collagenase. ACTH-(4–7), ACTH-(6–10), ACTH-(4–10) and ACTH-(11–13) stimulated corticosterone production of the zona fasciculata and aldosterone production of the zona glo

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 cheetah. No statistically significant rise was seen in the anaesthetised control group following the injection of saline (P = 0.238).

  17. Molecular transduction mechanisms in ACTH-induced grooming

    NARCIS (Netherlands)

    Gispen, W.H.; Colbern, D.; Spruijt, B.M.

    1988-01-01

    Intraventricular administration of ACTH1-24 induces excessive grooming in the rat. Ethogram analysis shows that the peptide does not alter grooming behavior seen in a novel box, but that it prolongs the duration of the grooming bout. Extensive structure-activity studies have been performed which sug

  18. Еctopic ACTH syndrome: clinical picture, diagnosis, treatment

    Directory of Open Access Journals (Sweden)

    N S Kuznetsov

    2012-03-01

    Full Text Available Diagnosis and treatment of ectopic ACTH-syndrome currently is one of the most challenging problems among other forms of endogenous hypercorticism. This syndrome is associated with presence of extrapituitary tumors characterized with different histogenesis and localization, which produce adrenocorticotropic hormone (ACTH, or – rarely – corticotrophin-releasing hormone. In most cases the ectopic synthesis of ACTH is performed in bronchial carcinoid tumors (36–46%, oat cell cancer (18–20%, medullary thyroid cancer (3–7%, pheochromocytoma (9–23%, other sites are infrequent (pancreas, thymus, parotid gland, ovaries, uterus, prostate, colon, stomach, esophagus, etc.. Much of these tumors are aggressive and are characterized with propensity to metastasize and relapse. Currently there are few contradictory data on the comparative evaluation of the effectiveness of methods of topical diagnosis of the source of ectopic ACTH-secretion, and therefore there is an urgent need to develop an optimal and most efficient algorithm for diagnostic procedures to determine the extent of the tumor in patients with ectopic ACTH-syndrome. Indications for surgery, timing and extent of surgical intervention, the effectiveness of the operation, the causes and frequency of relapses are still discussed.The present difficulties of diagnosis, as well as the lack of a unified approach to the treatment of this disease in the complex, often lead to the progression and development of a large number of serious complications functions of up to disability, which in turn does not lead to significant improvement of quality of life. Thus further research is necessary to study of this disease

  19. 60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH.

    Science.gov (United States)

    Gallo-Payet, Nicole

    2016-05-01

    The pituitary adrenocorticotropic hormone (ACTH) plays a pivotal role in homeostasis and stress response and is thus the major component of the hypothalamo-pituitary-adrenal axis. After a brief summary of ACTH production from proopiomelanocortin (POMC) and on ACTH receptor properties, the first part of the review covers the role of ACTH in steroidogenesis and steroid secretion. We highlight the mechanisms explaining the differential acute vs chronic effects of ACTH on aldosterone and glucocorticoid secretion. The second part summarizes the effects of ACTH on adrenal growth, addressing its role as either a mitogenic or a differentiating factor. We then review the mechanisms involved in steroid secretion, from the classical Cyclic adenosine monophosphate second messenger system to various signaling cascades. We also consider how the interaction between the extracellular matrix and the cytoskeleton may trigger activation of signaling platforms potentially stimulating or repressing the steroidogenic potency of ACTH. Finally, we consider the extra-adrenal actions of ACTH, in particular its role in differentiation in a variety of cell types, in addition to its known lipolytic effects on adipocytes. In each section, we endeavor to correlate basic mechanisms of ACTH function with the pathological consequences of ACTH signaling deficiency and of overproduction of ACTH.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  3. Reactive thymic hyperplasia following treatment of ACTH-producing tumors; Reaktive Thymushyperplasie infolge der Therapie ACTH-produzierender Tumoren

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    Schmidt, S.; Klose, K.J.; Iwinska-Zelder, J. [Abt. Strahlendiagnostik, Medizinisches Zentrum fuer Radiologie, Philipps-Universitaet Marburg (Germany); Frank, M.; Ehlenz, K. [Abt. Gastroenterologie, Zentrum fuer Innere Medizin, Philipps-Universitaet Marburg (Germany); Kisker, O. [Philipps-Universitaet Marburg (Germany). Abt. Allgemeine Chirurgie

    1997-11-01

    Surgical or conservative treatment of ACTH-producing tumors results in acute drop of the previously excessively high cortisol levels. The following associated pathophysiological changes also occur in the organism`s recovery from stress, such as trauma, operation or chemotherapy of tumors. Both cases result in a regeneration of the immune system, which might even be exalted. The corresponding radiographic feature is the `rebound` enlargement of the thymus occuring about six months after remission of hypercortisolism. Histological examination reveals benign thymus hyperplasia. Especially in cases of still unkown primary tumor the apperance of this anterior mediastinal mass can lead to misdiagnosis. We present the cases of two patients with diffuse thymic hyperplasia following surgical and medical correction of hypercortisolism. One patient suffered from classic Cushing`s disease responding to transsphenoidal resection of an ACTH-secreting pituitary microadenoma. Six monsths later CT of the chest incidentally demonstrated an anterior mediastinal mass known as thymic hyperplasia. The second patient presented with an ectopic, still unknown source of ACTH-production. (orig./AJ) [Deutsch] Durch operative oder medikamentoese Therapie von ACTH-produzierenden Tumoren wird der exzessiv erhoehte Kortisolspiegel abrupt korrigiert. Die damit verbundenen pathopysiologischen Veraenderungen entsprechen der Erholungsphase des Organismus nach extremer Stressbelastung durch Trauma, Operation oder Chemotherapie von Tumoren. In beiden Faellen kommt es zu einer - moeglicherweise sogar ueberschiessenden - Regeneration des Immunsystems. In der bildgebenden Diagnostik ist dies als `Rebound` thymushyperplasie zu beobachten. Diese ca. 6 Monate posttherapeutisch auftretende anteriore mediastinale Raumforderung kann besonders in Faellen von noch unbekanntem Primaertumor zu Fehldiagnosen Anlass geben. Anhand der beiden folgenden Kasuistiken wird versucht, den pathophysiologischen und zeitlichen

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  7. Effects of hypophysectomy and ACTH1–10 on responsiveness to electric shock in rats

    NARCIS (Netherlands)

    Gispen, W.H.; Wimersma Greidanus, T.B. van; Wied, D. de

    1967-01-01

    Response behavior of rats to unescapable electric shock was studied in intact and hypophysectomized animals. The threshold for flinch, jerk, run and jump was significantly lowered in hypophysectomized rats as compared to that of intact controls. Treatment with the ACTH analogue ACTH1–10 did not affe

  8. The effects of ACTH- and vasopressin-analogues on CO2-induced retrograde amnesia in rats

    NARCIS (Netherlands)

    Rigter, H.; Riezen, H. van; Wied, D. de

    1974-01-01

    Amnesia for a one-trial step-through passive avoidance response was induced in rats by application of CO2 until respiratory arrest occurred. The ACTH-analogue ACTH4–10 alleviated the amnesia when administered 1 hr prior to the retrieval test but not when given 1 hr prior to the acquisition trial. Th

  9. Effect of angiotensin II, catecholamines and glucocorticoid on corticotropin releasing factor (CRF-induced ACTH release in pituitary cell cultures.

    Directory of Open Access Journals (Sweden)

    Murakami,Kazuharu

    1984-08-01

    Full Text Available The effects of angiotensin II, catecholamines and glucocorticoid on CRF-induced ACTH release were examined using rat anterior pituitary cells in monolayer culture. Synthetic ovine CRF induced a significant ACTH release in this system. Angiotensin II produced an additive effect on CRF-induced ACTH release. The ACTH releasing activity of CRF was potentiated by epinephrine and norepinephrine. Dopamine itself at 0.03-30 ng/ml did not show any significant effect on ACTH release, but it inhibited CRF-induced ACTH release. Corticosterone at 10(-7 and 10(-6M inhibited CRF-induced ACTH release. These results indicate that angiotensin II, catecholamines and glucocorticoid modulate ACTH release at the pituitary level.

  10. Occult secretion of acth and bilateral adrenalectomy: sometimes the messenger has to be shot.

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    Chicharro, Sandra; Lecube, Albert; Mesa, Jordi

    2008-12-01

    Cushing's syndrome due to ectopic adrenocorticotrophic hormone (ACTH) secretion is infrequent, the most frequent cause being bronchial carcinoid; nevertheless, in a considerable proportion of cases (up to 16%), the origin of ACTH secretion is not found. Treatment of Cushing's syndrome due to ectopic ACTH secretion is surgical resection of the tumor. However, surgical excision is not always feasible, either because the tumor has not been located, or because it is unresectable; in these cases the question is when to carry out a bilateral adrenalectomy. We present a case of ACTH-dependent hypercortisolism, in which the ectopic origin of ACTH secretion was established from the results of complementary tests (suppression tests, petrosal sinus sampling, imaging); nevertheless, none of the imaging tests was able to identify the secreting tumor. Consequently, after a reasonable interval, a bilateral adrenalectomy was performed, with good clinical results.

  11. ACTH-producing neuroendocrine tumor of thymus with recurrences. Clinical case

    Directory of Open Access Journals (Sweden)

    E A Dobreva

    2015-06-01

    Full Text Available One of the most difficult in diagnostic and treatment options for endogenous Cushing is the ectopic ACTH syndrome, which causes the development of tumors of different histogenesis localization producing adrenocorticotropic hormone (ACTH, and much less - corticotropin hormone (CRH. ACTH-secreting tumors varied in location, morphological structure and the degree of malignancy. Most of these tumors are characterized by an aggressive course with a propensity to metastasize and relapse. The article presents data of the prevalence, pathogenesis of ectopic ACTH tumors localized in the thymus, analyzis of clinical, morphological features, the methods of diagnosis and treatment. Based on the current literature, the world and our own experience on the diagnosis and treatment of patients with ectopic ACTH syndrome with localization of hormone production in the thymus, we want to highlight the current state of the problem in order to create the most efficient algorithm for diagnostic search and treatment of this difficult group of patients.

  12. The inhibitory effect of ACTH 1–10 on extinction of a conditioned avoidance response: Its independence of thyroid function

    NARCIS (Netherlands)

    Wied, D. de; Pirie, Gail

    1968-01-01

    The effect of the ACTH analogue ACTH 1–10 was studied on the rate of extinction of a pole jumping avoidance response in thyroidectomized rats with or without replacement therapy with 1-thyroxin. ACTH 1–10 appeared to delay the rate of extinction of the CAR in thyroidectomized rats in a similar way a

  13. Immunohistochemical detection of ACTH and MSH cells in the hypophysis of the hermaphroditic teleost, Diplodus sargus.

    Science.gov (United States)

    Ferrandino, I; Pica, A; Grimaldi, M C

    2000-01-01

    Hypophyseal ACTH and MSH cells were immunohistochemically characterised in the teleost fish, Diplodus sargus, using anti-ACTH (1-24) and anti alpha-MSH polyclonal antisera. ACTH cells were found both in the pars distalis and in the pars intermedia. In the former region, they appeared small, round-shaped and clustered; in the latter, they were either small or large and elongated. Moreover, a few ACTH-immunoreactive cells resembling microglia were present in the neurohypophysis. Conversely, MSH cells were found only in the pars intermedia, and were similar to the larger ACTH cells of the same region. In the pars intermedia, co-localisation of ACTH and MSH immunoreactivity in the same cell was revealed by double immunostaining, though the two hormones were also observed in distinct cell types. The distribution of ACTH cells appeared quite uniform, without any marked difference between the specimens tested. Conversely, MSH cell amount varied according to the stage of the sexual cycle of this teleost fish, which is characterised by protandrous hermaphroditism. In fact, a lower amount of MSH cells were observed in females, whereas no significant difference was found between immature and male specimens.

  14. Immunohistochemical detection of acth and msh cells in the hypophysis of the hermaphroditic teleost, Diplodus sargus

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    M Consiglio Grimaldi

    2009-12-01

    Full Text Available Hypophyseal ACTH and MSH cells were immunohistochemically characterised in the teleost fish, Diplodus sargus, using anti-ACTH (1-24 and anti a-MSH polyclonal antisera. ACTH cells were found both in the pars distalis and in the pars intermedia. In the former region, they appeared small, round-shaped and clustered; in the latter, they were either small or large and elongated. Moreover, a few ACTH-immunoreactive cells resembling microglia were present in the neurohypophysis. Conversely, MSH cells were found only in the pars intermedia, and were similar to the larger ACTH cells of the same region. In the pars intermedia, co-localisation of ACTH and MSH immunoreactivity in the same cell was revealed by double immunostaining, though the two hormones were also observed in distinct cell types. The distribution of ACTH cells appeared quite uniform, without any marked difference between the specimens tested. Conversely, MSH cell amount varied according to the stage of the sexual cycle of this teleost fish, which is characterised by protandrous hermaphroditism. In fact, a lower amount of MSH cells were observed in females, whereas no significant difference was found between immature and male specimens.

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

    Science.gov (United States)

    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.

  16. Lipid synthesis and secretion in HepG2 cells is not affected by ACTH

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    Nilsson-Ehle Peter

    2010-05-01

    Full Text Available Abstract Apolipoprotein B (apoB containing lipoproteins, i.e. VLDL, LDL and Lp(a, are consequently lowered by ACTH treatment in humans. This is also seen as reduced plasma apoB by 20-30% and total cholesterol by 30-40%, mostly accounted for by a decrease in LDL-cholesterol. Studies in hepatic cell line (HepG2 cells showed that apoB mRNA expression is reduced in response to ACTH incubation and is followed by a reduced apoB secretion, which may hypothesize that ACTH lowering apoB containing lipoproteins in humans may be mediated by the inhibition of hepatic apoB synthesis. This was recently confirmed in vivo in a human postprandial study, where ACTH reduced transient apoB48 elevation from the small intestine, however, the exogenic lipid turnover seemed unimpaired. In the present study we investigated if lipid synthesis and/or secretion in HepG2 cells were also affected by pharmacological levels of ACTH to accompany the reduced apoB output. HepG2 cells were incubated with radiolabelled precursors ([14C]acetate and [3H]glycerol either before or during ACTH stimuli. Cellular and secreted lipids were extracted with chloroform:methanol and separated by the thin layer chromatography (TLC, and [14C]labelled cholesterol and cholesteryl ester and [3H]labelled triglycerides and phospholipids were quantitated by the liquid scintillation counting. It demonstrated that ACTH administration did not result in any significant change in neither synthesis nor secretion of the studied lipids, this regardless of presence or absence of oleic acid, which is known to stabilize apoB and enhance apoB production. The present study suggests that ACTH lowers plasma lipids in humans mainly mediated by the inhibition of apoB synthesis and did not via the reduced lipid synthesis.

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

    Science.gov (United States)

    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.

  18. ACTH Prevents Deficits in Fear Extinction Associated with Early Life Seizures

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    Andrew T Massey

    2016-05-01

    Full Text Available Early life seizures are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of early life seizures (ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action. We found that while rats with a history of ELS were able to acquire a conditioned fear learning paradigm as well as controls, these rats had significant deficits in their ability to extinguish fearful memories. ACTH treatment did not alter any seizure parameters but nevertheless was able to significantly improve this fear extinction, while dexamethasone treatment during the same period did not. This ACTH effect was specific for fear extinction deficits and not for spatial learning deficits in a water maze. Additionally, ACTH did not alter seizure latency or duration suggesting that cognitive and seizure outcomes may be dissociable. Expression levels of melanocortin receptors, which bind ACTH, were found to be significantly lower in animals that had experienced ELS than in control animals, potentially implicating central melanocortin receptor dysregulation in the effects of ELS and suggesting a mechanism of action for ACTH. Taken together, these data suggest that early treatment with ACTH can have significant long-term consequences for cognition in animals with a history of ELS independently of seizure cessation, and may act in part through a CNS melanocortin receptor pathway.

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

    Science.gov (United States)

    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.

  20. Gene array analysis of adrenal glands in broiler chickens following ACTH treatment

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    Guémené Daniel

    2009-09-01

    Full Text Available Abstract Background Difference in adaptability responses to stress has been observed amongst bird species, strains, and individuals. Components of the HPA axis, one of the internal systems involved in homeostasis re-establishment following stress, could play a role in this variability of responses. The aim of the present study was 1 to identify genes involved in the regulation of adrenal activity following ACTH stimulation and 2 to examine adrenal genes differentially expressed in individuals with high and low plasma corticosterone response following ACTH treatment. Results Analysis with 21 K poultry oligo microarrays indicated that ACTH treatment affected the expression of 134 genes. Several transcripts assigned to genes involved in the adrenal ACTH signaling pathway and steroidogenic enzymes were identified as differentially expressed by ACTH treatment. Real-time PCR on 18 selected genes confirmed changes in transcript levels of 11 genes, including MC2R, CREM, Cry, Bmal1, Sqle, Prax1, and StAR. Only 4 genes revealed to be differentially expressed between higher and lower adrenal responders to ACTH treatment. Conclusion The results from the present study reveal putative candidate genes; their role in regulation of adrenal functions and adaptability to stress should be further investigated.

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

    Science.gov (United States)

    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.

  2. Decrease of N-acetylaspartate after ACTH therapy in patients with infantile spasms.

    Science.gov (United States)

    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.

  3. Catheterization during adrenal vein sampling for primary aldosteronism: failure to use (1-24) ACTH may increase apparent failure rate.

    Science.gov (United States)

    Kline, Gregory A; So, Benny; Dias, Valerian C; Harvey, Adrian; Pasieka, Janice L

    2013-07-01

    "Successful" adrenal vein catheterization in primary aldosteronism (PA) is often defined by a ratio of >3:1 of cortisol in the adrenal vein vs the inferior vena cava. Non-use of corticotropin (ACTH) during sampling may increase the apparent failure rate of adrenal vein catheterization due to lower cortisol levels. A retrospective study was performed on all patients with confirmed unilateral PA between June 2005 and August 2011. Adrenal vein sampling (AVS) included simultaneous bilateral baseline samples with repeat sampling 15 minutes after intravenous infusion of 250 μg of Cortrosyn (ACTH-S). Successful catheter placement was judged as adrenal cortisol:IVC cortisol of >3:1, applied to both baseline and ACTH-S samples and lateralization of aldosteronism was judged as normalized aldosterone/cortisol (A/C) ratio >3 times the contralateral A/C ratio. In ACTH-S samples, 94% of right-sided catheterizations were biochemically successful with 100% success on the left. Among baseline samples, only 47% of right- and 44% of left-sided samples met the 3:1 cortisol criteria. However, 95% of apparent "failed" baseline cortisol sets still showed lateralization of A/C ratios that matched the ultimate pathology. Non-ACTH-stimulated samples may be incorrectly judged as failed catheter placement when a 3:1 ratio is used. ACTH-stimulated sampling is the preferred means to confirm catheterization during AVS.

  4. Response of plasma cortisol and progesterone after ACTH challenge in ovariectomized lactating dairy cows.

    Science.gov (United States)

    Yoshida, Chikako; Nakao, Toshihiko

    2005-02-01

    Shortened and weakened estrous expressions could be one of the causes of poor heat detection rate. Non-specific acute stresses are assumed to depress expression of estrus by an increase of plasma progesterone which may originate from the adrenal cortex. The objective of the present study was to examine whether the adrenal cortex can secrete significant amounts of progesterone in response to exogenous adrenocorticotropic hormone (ACTH) in lactating cows. Four cows had estrus synchronized and were ovariectomized in the luteal phase. The cows were given 25 IU ACTH through an indwelling catheter 5 h after catheterization. Blood samples were collected at an interval of 30 min. In 3 of the 4 cows, plasma progesterone concentrations increased significantly 0.5-1.5 h after the first ACTH challenge with a mean peak value of 4.2 +/- 0.4 (S.D.) ng/ml. A similar response was also observed after the second ACTH challenge. Peak plasma progesterone concentrations in the 3 cows after first ACTH challenge were comparable with the progesterone values in the luteal phase of each cow. The results suggest that lactating cows have the capability to secrete a significant amount of progesterone from the adrenal cortex.

  5. A case of ACTH-independent bilateral macronodular adrenal hyperplasia and severe congestive heart failure.

    Science.gov (United States)

    Suri, D; Alonso, M; Weiss, R E

    2006-11-01

    Cortisol secretion in ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH) can be regulated by aberrant adrenal receptors. We describe a patient with Cushing's syndrome (CS) due to AIMAH and concomitant Class IV congestive heart failure (CHF). Clinical testing for the presence of aberrant receptors revealed a pronounced serum cortisol (257%) and aldosterone response (212%) to the administration of ACTH and a partial serum cortisol (35%) and aldosterone (106%) response to upright posture. This suggested the possible presence of aberrant hormone receptors for ACTH [melanocortin 2 receptor (MC2-R)], vasopressin, catecholamines or angiotensin II (AT-II) on the patient's adrenal glands. Adrenal tissue from the patient demonstrated an eight-fold increased expression of MC2-R compared to normal adrenal tissue. This increased expression was consistent with the increase in cortisol and aldosterone seen in response to exogenous ACTH. We propose that the severe CHF resulted in activation of the renin-angiotensin system, with an increased production of AT-II. The elevated circulating levels of AT-II may have led to increased expression of MC2-R on the patient's adrenal glands and increased responsiveness to ACTH. This unusual case of CS may elucidate a heretofore unknown mechanism for the development of AIMAH.

  6. Beta-endorphin and ACTH in plasma during attacks of common and classic migraine

    DEFF Research Database (Denmark)

    Bach, F W; Jensen, K; Blegvad, N;

    1985-01-01

    Plasma levels of beta-endorphin and ACTH were measured during and outside migraine attacks in 17 patients with common migraine and 11 patients with classic migraine. Specific radioimmunoassays for beta-endorphin and ACTH were used. The beta-endorphin assay did not cross-react with beta......-lipotropin. In common migraine, median plasma beta-endorphin was 3.3 pmol/l (95% confidence limits: 2.5-4.0 pmol/l) during attacks and 2.9 (2.4-3.2) pmol/l in the headache-free period. In classic migraine, plasma beta-endorphin was 3.2 (1.4-4.3) pmol/l during attacks and 2.4 (1.1-3.6) pmol/l outside attacks. ACTH...

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

    Science.gov (United States)

    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).

  8. COMPARATIVE EFFECTS OF NITRAZEPAM AND ACTH ON THE TREATMENT OF INFANTILE SPASM

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    MM. Taghdir

    2007-08-01

    Full Text Available ObjectiveInfantile spasms (IS or West syndrome is a convulsive disease characterizedby brief, symmetric axial muscle contractions (neck, trunk, and/or extremities.The therapy universally recognized as most effective in the treatment of IS,is treatment with the adrenocorticotropic hormone (ACTH or oral corticosteroids.This therapy however has important side effects. Many studies have soughtto find alternative therapies with fewer side effects. Nitrazepam, it has beenproven, can be as effective as ACTH in controlling infantile spasms. The aimof this study was to evaluate and compare the efficacy of Nitrazepam andACTH on the treatment of infantile spasms.Materials & MethodsThis randomized controlled clinical trial, enrolled sixty patients with newlydiagnosed and previously untreated IS; diagnosis was made based on thecriteria of The International Classification of Epilepsies of the InternationalLeague Against Epilepsy (ILAE. Prior to treatment, all patients underwentElectro encephalo graphs (EEGs and CT scans. Patients were randomized toreceive 0.5-1 mg/kg Nitrazpam (NZP in three daily doses or 40 IU DepotACTH in a single morning dose. Complete cessation of spasms was consideredto be as optimal response.ResultsOf the sixty patients studied, 24 (40% were girls and 36(60% were boys. Allpatients in the both groups were matched for age and sex.There were nodifferences between the both groups regarding age and sex (non-significant.Following treatments, at the end of the 6-week duration therapy, optimalresponse (Cessation of spasms was obtained in 19 (63% patients of NZPgroup and 9 (30% patients of ACTH group, (P0.05.ConclusionThis study supports the belief that NZP offers an effective and possibly safertherapy than ACTH, for the management of IS and that the therapeuticresponse, if imminent, can be detected within 4-6 weeks of treatment. Cliniciansshould consider using NZP as a first-line therapy for IS.

  9. Loss of sensitivity to ACTH of adrenocortical cells isolated from maturing domestic fowl.

    Science.gov (United States)

    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.

  10. [1H-NMR studies of the ACTH-like immunoregulatory peptides].

    Science.gov (United States)

    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.

  11. Severe Hypoglycemia due to Isolated ACTH Deficiency in Children: A New Case Report and Review of the Literature

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    Michael Y. Torchinsky

    2011-01-01

    Full Text Available Isolated ACTH deficiency causes life-threatening severe hypoglycemia. A 7-year-old girl with hypoglycemia due to this rare disorder is described. Our patient had undetectable plasma ACTH repeatedly and cortisol 0 mcg/dl before and after ACTH 1-24 stimulation. There was no evidence of other pituitary hormone deficiency. Glucocorticoid replacement therapy resulted in resolution of all symptoms and normalization of blood glucose. Previously published data on isolated ACTH deficiency in children is summarized. Review of the literature showed that the prevalence of this condition could be underestimated in the neonatal period and in Prader-Willi syndrome. Isolated ACTH deficiency occurs in older children as well as in neonates.

  12. Corticotropin (ACTH)-reactive immunoglobulins in adolescents in relation to antisocial behavior and stress-induced cortisol response. The TRAILS study.

    Science.gov (United States)

    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, pantisocial 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.

  13. Beta-endorphin and ACTH in plasma during attacks of common and classic migraine

    DEFF Research Database (Denmark)

    Bach, F W; Jensen, K; Blegvad, N

    1985-01-01

    Plasma levels of beta-endorphin and ACTH were measured during and outside migraine attacks in 17 patients with common migraine and 11 patients with classic migraine. Specific radioimmunoassays for beta-endorphin and ACTH were used. The beta-endorphin assay did not cross-react with beta......-lipotropin. In common migraine, median plasma beta-endorphin was 3.3 pmol/l (95% confidence limits: 2.5-4.0 pmol/l) during attacks and 2.9 (2.4-3.2) pmol/l in the headache-free period. In classic migraine, plasma beta-endorphin was 3.2 (1.4-4.3) pmol/l during attacks and 2.4 (1.1-3.6) pmol/l outside attacks. ACTH...... plasma levels were 15 (10.5-20) pmol/l during and 15.7 (13.4-17) pmol/l outside attacks in common migraine. In classic migraine, plasma ACTH was 16 (7-36) pmol/l and 12.3 (8-28) pmol/l respectively. No significant differences were found between attacks and headache-free periods in common or classic...

  14. Short-term effects of ACTH on protein synthesis in adrenal cortex cells of young rats.

    Science.gov (United States)

    Magalhães, M C; Magalhães, M M; Cimbra, A

    1975-11-19

    Two units of ACTH were administered intraperitoneally to young 20 gm-rats which received an intravenous injection of L-leucine-3H thirteen min later. ACTH-injected rats, and control rats which received the isotope alone, were killed at 2-, 10-, 30- and 60-min intervals. Electron microscope autoradiographs in control animals showed strong amino-acid uptake at pulse time (2-min) in the cytoplasm of adrenal zona fasciculata cells. Label was shared between the endoplasmic reticulum (ER) and mitochondria, and a lower but still considerable uptake was seen in nucleoli. At first chase time interval (10-min) cytoplasmic labelling declined, while nuclear and nucleolar labelling increased, both changing little thereafter, and there was a 10-30 min Golgi peak. ACTH administration provoked an overall increase in amino-acid incorporation into cytoplasm, nucleus and nucleolus at pulse time, with no changes in the distribution of the reactions among organelles. Intensification of labelling was most evident over nucleoli, the grain density of which was four-times as high as in controls. The short-term increase in ER and mitochondrial protein synthesis observed after ACTH injections was considered to be consistent with the hypothesis that most newly-formed proteins in these cells may be involved in the regulation of steroidogenesis. The marked increase in nucleolar labelling suggested the presence of proteins involved in RNA synthesis.

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

    Science.gov (United States)

    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.

  16. Acute effects of ACTH on dissociated adrenocortical cells: quantitative changes in mitochondria and lipid droplets.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

    2015-10-01

    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: O ne 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sarma, Asha, E-mail: ashasarma@gmail.com; Shyn, Paul B., E-mail: pshyn@partners.org [Brigham and Women’s Hospital, Department of Radiology (United States); Vivian, Mark A. [University of Manitoba, Department of Radiology (Canada); Ng, Ju-Mei [Brigham and Women’s Hospital, Department of Anesthesiology (United States); Tuncali, Kemal [Brigham and Women’s Hospital, Department of Radiology (United States); Lorch, Jorchen H. [Dana Farber Cancer Institute, Department of Medicine (United States); Zaheer, Sarah N.; Gordon, Michael S. [Brigham and Women’s Hospital, Department of Endocrinology (United States); Silverman, Stuart G. [Brigham and Women’s Hospital, Department of Radiology (United States)

    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.

  20. Interactions of histaminergic and serotonergic neurons in the hypothalamic regulation of prolactin and ACTH secretion.

    Science.gov (United States)

    Jørgensen, H; Knigge, U; Kjaer, A; Warberg, J

    1996-11-01

    Serotonergic and histaminergic neuronal systems are both involved in mediation of the stress-induced release of the pituitary hormones prolactin (PRL) and ACTH. We investigated the possibility of an interaction between serotonin (5-HT) and histamine (HA) in regulation of PRL and ACTH secretion in conscious male rats. Animals were pretreated systemically with antagonists to 5-HT1, 5-HT2 or 5-HT3 receptors prior to intracerebroventricular (icv) administration of HA. The 5-HT1 + 2 receptor antagonist methysergide prevented and the 5-HT2 receptor antagonist LY 53857 attenuated the HA-induced PRL release while the 5-HT3 receptor antagonist ondansetron had no effect on this response. None of the three 5-HT receptor antagonists affected the ACTH response to HA. Specific blockade of HA synthesis by alpha-fluoromethylhistidine or blockade of postsynaptic HA receptors by icv infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine inhibited the PRL response to 5-HT or to the 5-HT precursor 5-hydroxytryptophan (5- HTP) given in combination with the 5-HT reuptake inhibitor fluoxetine (Flx). Blockade of the histaminergic system had no effect on the ACTH response to serotonergic stimulation. The H3 receptors are inhibitory HA receptors. Systemic pretreatment with the H3 receptor agonist R(alpha)methylhistamine, or the H3 receptor antagonist thioperamide had no effect on the hormone response to activation of the serotonergic system by 5-HTP plus Flx. We conclude that the serotonergic and histaminergic neuronal systems interact in their stimulation of PRL secretion, but not in their stimulation of ACTH secretion. This interaction involves serotonergic 5-HT1 and 5-HT2 receptors and histaminergic H1 and H2 receptors. Furthermore, the previously observed inhibitory effect of the H3 receptor agonist R(alpha)methylhistamine on stress-induced PRL and ACTH release seems not to be exerted by activation of presynaptic H3 receptors located on serotonergic

  1. The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin.

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    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

  2. Clinical, biological and genetic analysis of 8 cases of congenital isolated adrenocorticotrophic hormone (ACTH deficiency.

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    Luu-Ly Pham

    Full Text Available BACKGROUND: Congenital isolated adrenocorticotrophic hormone (ACTH deficiency may be rare, but it could be an underestimated cause of neonatal death. Our objective was to shorten the time between first symptoms and diagnosis. METHODS: This single-centre retrospective case-cohort study was carried out on eight consecutive patients. RESULTS: Two had the neonatal form and 6 the late onset form. Six were admitted to an intensive care unit at least once for seizures with hypoglycemia, major hypothermia, fever, and/or collapsus. The 2 neonatal cases presented with hypoglycemia and in a state of "apparent death" at birth or hypothermia (29°C at 6 days. All 6 late onset cases had also been admitted to an emergency department 1-3 times, but had left hospital incorrectly diagnosed. Their first symptoms were noted at 3-12.3 years, and they were diagnosed at 3.3-14.4 years. All had hypoglycemia, and 4 had had seizures. The presenting symptoms were vomiting and/or abdominal pain, asthenia, irritability, difficulty with physical activities, and anorexia. The school performance of 4 deteriorated. Two underwent psychotherapy and treatment for depression, which was stopped when Hydrocortisone® replacement therapy began. The plasma concentrations in spontaneous hypoglycemia were: ACTH<5 to 17.1 pg/mL, with concomitant cortisol <3.5 to 37 ng/mL. The plasma dehydroepiandrosterone sulfate (DHAS concentrations were low in the 7 evaluated. The coding sequence of TPIT was normal in all. CONCLUSION: Several unexplained symptoms in a child, mainly gastro-intestinal symptoms and seizures due to hypoglycemia, may indicate ACTH deficiency. A low or normal basal plasma ACTH despite concomitant low cortisol at 8 a.m. and/or in spontaneous hypoglycemia, associated with low DHAS, in a patient not given corticosteroids is highly suggestive of ACTH deficiency. The isolated character of ACTH deficiency must be confirmed by determining the other hypothalamic-pituitary functions

  3. COMPARATIVE EFFECTS OF NITRAZEPAM AND ACTH ON THE TREATMENT OF INFANTILE SPASM

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    MM. Taghdiri MD

    2009-01-01

    Full Text Available ObjectiveInfantile spasms (IS or West syndrome is a convulsive disease characterized by brief, symmetric axial muscle contractions (neck, trunk, and/or extremities.The therapy universally recognized as most effective in the treatment of IS, is treatment with the adrenocorticotropic hormone (ACTH or oral corticosteroids. This therapy however has important side effects. Many studies have sought to find alternative therapies with fewer side effects. Nitrazepam, it has been proven, can be as effective as ACTH in controlling infantile spasms. The aim of this study was to evaluate and compare the efficacy of Nitrazepam and ACTH on the treatment of infantile spasms. Materials & MethodsThis randomized controlled clinical trial, enrolled sixty patients with newly diagnosed and previously untreated IS; diagnosis was made based on the criteria of The International Classification of Epilepsies of the International League Against Epilepsy (ILAE. Prior to treatment, all patients underwent Electro encephalo graphs (EEGs and CT scans. Patients were randomized to receive 0.5-1 mg/kg Nitrazpam (NZP in three daily doses or 40 IU Depot ACTH in a single morning dose. Complete cessation of spasms was considered to be as optimal response.ResultsOf the sixty patients studied, 24 (40% were girls and 36(60% were boys. All patients in the both groups were matched for age and sex.There were no differences between the both groups regarding age and sex (non-significant. Following treatments, at the end of the 6-week duration therapy, optimal response (Cessation of spasms was obtained in 19 (63% patients of NZP group and 9 (30% patients of ACTH group, (P0.05.ConclusionThis study supports the belief that NZP offers an effective and possibly safer therapy than ACTH, for the management of IS and that the therapeutic response, if imminent, can be detected within 4-6 weeks of treatment. Clinicians should consider using NZP as a first-line therapy for IS

  4. Comparative effect of ACTH and related peptides on proliferation and growth of rat adrenal gland

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    Claudimara Ferini Pacicco Lotfi

    2016-05-01

    Full Text Available 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.

  5. [Stress hormones liberated by fangotherapy. ACTH and beta-endorphin levels under heat stress].

    Science.gov (United States)

    Giusti, P; Cima, L; Tinello, A; Cozzi, F; Targa, L; Lazzarin, P; Todesco, S

    1990-11-10

    In 6 healthy subjects submitted to fango therapy in the Euganean thermal baths (Italy), the plasma concentrations of beta-endorphin and ACTH increased transitorily but significantly. These results correlate with the release of these peptides by the pituitary in response to thermal stressing. The analgesic and hypothermic action responsible for good toleration of thermal stress induced by fango therapy, can be explained by this increase in plasma beta-endorphin. The repeated brief increases in plasma beta-endorphin during thermal treatment result in progressive improvement in articular and muscular symptomatology. The results of our study on plasma levels of ACTH confirm that the thermal stress associated with fango therapy activates the pituitary gland. Immunomodulatory effects are discussed.

  6. Severe hypokalemia, metabolic alkalosis and hypertension in a 54 year old male with ectopic ACTH syndrome: a case report

    OpenAIRE

    Martínez-Valles, Miguel Angel; Palafox-Cazarez, Asael; Paredes-Avina, Jose Antonio

    2009-01-01

    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. E...

  7. The role of ACTH and adrenal glucocorticoids in the salt appetite of wild rabbits (Oryctolagus cuniculus (L)).

    Science.gov (United States)

    Blaine, E H; Covelli, M D; Denton, D A; Nelson, J F; Shulkes, A A

    1975-10-01

    The selective appetites of wild rabbits for 500 mEq/1 solutions of NaC1, KC1, MgC1(2), and CaC1(2) were studied in intact and adrenalectomized rabbits during daily treatment with either 4 IU long acting ACTH, 1.0 or 2.5 mg cortisol acetate, or 2.5 mg corticosterone. The animals were individually caged and external sodium balances performed. In intact rabbits, cortisol or corticosterone produced a significant stimulation of NaC1 appetite. The response to concurrent dosage of cortisol and corticosterone was less than half of that obtained with ACTH which produced a comparable alteration of blood glucocorticoid levels but a 10-fold increase in NaC1 intake. CaC1(2) intake was increased in intact rabbits by cortisol treatment but not by corticosterone or ACTH. Adrenalectomized rabbits maintained on daily steroid replacement therapy of 0.1 mg deoxycorticosterone acetate and 0.75 mg cortisone acetate showed a normal pattern of electolyte, food, and water intake. Under these conditions ACTH produced a 4-fold increase in NaC1 intake. Further addition of cortisol and corticosterone to steroid replacement therapy produced an increase in NaC1 intake comparable to their effect on normal rabbits. Thereupon supplementation with ACTH resulted in an increase to a level at least as great as that found in ACTH treated, normal rabbits. The effects of ACTH and glucocorticoids on NaC1 appetite were synergistic. Sodium balance showed that increases in NaC1 intake were not the result of the treatment initially producing a body sodium deficit, which was then corrected by increased intake. The results provide further evidence for the hypothesis that NaC1 appetite may be hormonally regulated, and demonstrate that ACTH is capable of stimulating NaC1 intake by a previously unsuspected non-adrenal pathway.

  8. Use of adrenal arterial embolization in severe ACTH-dependent Cushing's syndrome.

    OpenAIRE

    Blunt, S B; Pirmohamed, M.; Chatterjee, V K; Burrin, J. M.; Allison, D J; Joplin, G. F.

    1989-01-01

    The management of a patient with severe Cushing's syndrome due to ectopic ACTH produced by a medullary carcinoma of the thyroid is described. Initial treatment with maximal adrenolytic medical therapy and two attempts at bilateral adrenal venous infarction had failed to control the disease, and she was at that time unfit for surgery. Subsequent use of bilateral adrenal arterial embolization enabled medical therapy to produce sufficient control of the Cushing's syndrome to allow bilateral adre...

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

    Science.gov (United States)

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

    Science.gov (United States)

    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.

  11. Using ACTH Challenges to Validate Techniques for Adrenocortical Activity Analysis in Various African Wildlife Species

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    Diana M. Armstrong

    2012-04-01

    Full Text Available Monitoring adrenocortical activity using fecal hormonal analysis can provide information on how environmental changes are affecting non-domestic species health and success in the field; however, this noninvasive method needs proper validation to ensure that analysis reflects true physiological events. Our objectives were to use adrenocorticotropic hormone (ACTH challenges as a physiological validation method to test the suitability of a new corticosterone enzyme immunoassay (EIA to accurately assess the adrenocortical activity using fecal samples in four African wildlife species-the black rhinoceros (rhino; Diceros bicornis, African elephant (Loxodonta africana, chimpanzee (Pan troglodytes and African lion (Panthera leo krugeri. In the rhino and elephant, fecal Glucocorticoid metabolites (GC surged 75 and 51 h post-ACTH injection, respectively. In the chimpanzee, fecal GC metabolites peaked at 29 h post-injection. And the lion had a peak of fecal GC at 24 h post-ACTH. This study determined that adrenocortical activity was reflected in concentrations of fecal GC metabolites suggesting that this corticosterone EIA is an effective technique for the monitoring stress in four African species.

  12. Tratamento das formas severas de miastenia pelo ACTH por via intravenosa

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    José Lamartine de Assis

    1960-12-01

    Full Text Available O autor inicia o trabalho referindo as bases bioquímicas, fisiopatológicas e anátomo-patológicas do tratamento da miastenia pelo ACTH. Na miastenia grave há diminuição da síntese da acetilcolina no organismo, atuando o ACTH no sentido de aumentar esta síntese seja diretamente, por ativação da colinacetilase, seja indiretamente, mediante a redução da massa dos tecidos linfóides, em particular do timo, responsáveis pela elaboração de substâncias que diminuem a síntese da acetilcolina. O autor empregou o ACTH "Armour" e a Cortrofina "Organon", nas doses de 2,5 a 25 mg, sempre pela via intravenosa, diluídos em 250 a 1.000 ml de soluto glicosado a 5%, administrado gota a gôta, na velocidade média de 20 gôtas por minuto, durante 8 horas. Como medicação associada foi administrada a Prostigmina a todos os pacientes, substituída, depois, em alguns casos, pelo Mestinon ou pela Mytelaze. Como adjuvantes foram empregados o cloreto de potássio (2 a 8 g por dia e o sulfato de efedrina (25 mg 3 vêzes ao dia. Os pacientes foram mantidos em regime hiperprotéico e acloretado, sendo tomados todos os cuidados inerentes ao uso do ACTH. Foram estudados 10 pacientes portadores de miastenia com sintomatologia acentuada (8 casos e média (2 casos. Todos os doentes vinham sendo tratados com drogas anticolinesterásicas em doses adequadas (Prostigmina, Mestinon, Mytelaze e a sua sintomatologia respondia cada vez menos a esta terapêutica. Em alguns casos haviam sido tentados outros tratamentos (timectomia, denervação do seio carotídeo, irradiação da região tímica sem resultado. É de notar que as remissões espontâneas neste grupo de enfermos foram excepcionais e de curta duração. A evolução foi acompanhada do ponto de vista clínico, com a sintomatologia classificada como muito acentuada, acentuada, média e leve. Em todos os casos houve remissão completa ou quase completa da sintomatologia após dosagens variáveis de ACTH; no

  13. The Recombinant ACTH (4-10) -GDNF Fusion Protein and Study ofIts Biological Activity%重组ACTH(4-10)与GDNF融合蛋白及其生物活性研究

    Institute of Scientific and Technical Information of China (English)

    陈哲宇; 张勇; 何成; 路长林; 吴祥甫

    2001-01-01

    通过PCR方法构建了促肾上腺皮质激素4-10(ACTH(4-10))与胶质细胞源性神经营养因子(GDNF)的 融合基因,并将它重组克隆到表达载体pET-28a(+)中,构建表达质粒pET-ACTH(4-10)-GDNF,转化大肠 杆菌BL21(DE3),经IPTG诱导可高效表达ACTH(4-10)-GDNF融合蛋白.用Ni2+-NTA树脂一步法纯化目 的蛋白,纯度达85%以上.纯化和复性的ACTH(4-10)-GDNF融合蛋白能显著促进脊髓神经元存活,作用强 于ACTH(4-10)及GDNF蛋白.%The chimeric gene of ACTH (4-10) with GDNF was constructed by PCR amplification. The fused gene was inserted into the expression vector pET-28a ( + ) and expressed in E. coli . with a level of 30% of the total bacterial proteins. The expressed product was purified by Ni2+ -NTA resin, up to 85% purity. The results of activity assays showed that the chimeric protein could significantly promote the survival of spinal cord neurons and had a higher neurotrophic activity than ACTH (4-10) and GDNF respectively.

  14. Impact of ACTH administration on the oviductal sperm reservoir in sows: the local endocrine environment and distribution of spermatozoa.

    Science.gov (United States)

    Brandt, Y; Lang, A; Madej, A; Rodriguez-Martinez, H; Einarsson, S

    2006-03-01

    The objective of the study was to investigate if short-term stress in sows (simulated by injections of synthetic adrenocorticotrophic hormone (ACTH)) during standing oestrus had a negative effect on the local environment in the utero-tubal junction (UTJ) and isthmus and the distribution of spermatozoa in these segments. Fourteen sows were monitored for ovulation using ultrasonography in two consecutive oestruses. The sows were fitted with jugular catheters and, from onset of the second oestrus, blood samples were collected every second hour. In the 2nd oestrus, seven sows were given ACTH every second hour, from the onset of standing oestrus until the sow ovulated (ACTH-group), whereas the other seven sows remained as controls (C-group) and were given NaCl solution. The sows were artificially inseminated 16-18 h before expected ovulation. Six hours after ovulation the sows were anaesthetised, and blood samples were repeatedly taken from veins draining the uterus and the UTJ-isthmus, respectively. This oviduct was thereafter removed and divided in four adjacent sections consisting of: (i) the UTJ, (ii) the first, and (iii) the second isthmus segment prior to (iv), the ampullary-isthmic junction (AIJ) and the ampulla. The three first-mentioned segments were flushed to retrieve spermatozoa, whereas the last one was flushed to collect oocytes/ova. The number of spermatozoa attached to the zona pellucida was counted. The concentrations of cortisol in jugular blood of the ACTH-group sows during the time of ACTH-injections were significantly higher than of the C-group sows (pAIJ. In conclusion, simulated stress induced by injections of ACTH during standing oestrus results in elevated concentrations of progesterone before ovulation and may interfere with the rise of progesterone after ovulation. However, ACTH-injections appeared to augment transport of spermatozoa through the female genital tract of pigs.

  15. A patient with recurrent hypercortisolism after removal of an ACTH-secreting pituitary adenoma due to an adrenal macronodule.

    Science.gov (United States)

    Timmers, H J L M; van Ginneken, E M; Wesseling, P; Sweep, C G J; Hermus, A R M M

    2006-11-01

    A 41-yr-old female was referred for signs and symptoms of Cushing's syndrome. Cortisol was not suppressed by 1 mg dexamethasone (0.41 micromol/l). Midnight cortisol and ACTH were 0.44 micromol/l and 18 pmol/l, respectively. Urinary cortisol excretion was 250 nmol/24 h (normal between 30 and 150 nmol/24 h). A magnetic resonance imaging (MRI) revealed a pituitary lesion of 7 mm. ACTH and cortisol levels were unaltered by administration of human CRH and high-dose dexamethasone. Inferior sinus petrosus sampling showed CRH-stimulated ACTH levels of 128.4 (left sinus) vs a peripheral level of 19.2 pmol/l, indicating Cushing's disease. After 4 months of pre-treatment with metyrapone and dexamethasone, endoscopic transsphenoidal resection of an ACTH-positive pituitary adenoma was performed. ACTH levels decreased to 2.6 pmol/l and fasting cortisol was 0.35 micromol/l. Despite clinical regression of Cushing's syndrome and normalization of urinary cortisol, cortisol was not suppressed by 1 mg dexamethasone (0.30 micromol/l). Ten months post-operatively, signs and symptoms of Cushing's syndrome reoccurred. A high dose dexamethasone test according to Liddle resulted in undetectable ACTH, but no suppression of cortisol levels, pointing towards adrenal-dependent Cushing's syndrome. Computed tomography (CT)-scanning showed a left-sided adrenal macronodule. Laparoscopic left adrenalectomy revealed a cortical macronodule (3.5 cm) surrounded by micronodular hyperplasia. Fasting cortisol had decreased to 0.02 micromol/l. Glucocorticoid suppletion was started and tapered over 12 months. Symptoms and signs of hypercortisolism gradually disappeared. This case illustrates, that longstanding ACTH stimulation by a pituitary adenoma can induce unilateral macronodular adrenal hyperplasia with autonomous cortisol production.

  16. Comparison of salivary and calculated free cortisol levels during low and standard dose of ACTH stimulation tests in healthy volunteers.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  18. ACTH-Independent Cushing’s Syndrome with Bilateral Micronodular Adrenal Hyperplasia and Ectopic Adrenocortical Adenoma

    Science.gov (United States)

    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

  19. Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH.

    Directory of Open Access Journals (Sweden)

    Amanda E Hernan

    Full Text Available Children with epilepsy often present with pervasive cognitive and behavioral comorbidities including working memory impairments, attention deficit hyperactivity disorder (ADHD and autism spectrum disorder. These non-seizure characteristics are severely detrimental to overall quality of life. Some of these children, particularly those with epilepsies classified as Landau-Kleffner Syndrome or continuous spike and wave during sleep, have infrequent seizure activity but frequent focal epileptiform activity. This frequent epileptiform activity is thought to be detrimental to cognitive development; however, it is also possible that these IIS events initiate pathophysiological pathways in the developing brain that may be independently associated with cognitive deficits. These hypotheses are difficult to address due to the previous lack of an appropriate animal model. To this end, we have recently developed a rat model to test the role of frequent focal epileptiform activity in the prefrontal cortex. Using microinjections of a GABA(A antagonist (bicuculline methiodine delivered multiple times per day from postnatal day (p 21 to p25, we showed that rat pups experiencing frequent, focal, recurrent epileptiform activity in the form of interictal spikes during neurodevelopment have significant long-term deficits in attention and sociability that persist into adulthood. To determine if treatment with ACTH, a drug widely used to treat early-life seizures, altered outcome we administered ACTH once per day subcutaneously during the time of the induced interictal spike activity. We show a modest amelioration of the attention deficit seen in animals with a history of early life interictal spikes with ACTH, in the absence of alteration of interictal spike activity. These results suggest that pharmacological intervention that is not targeted to the interictal spike activity is worthy of future study as it may be beneficial for preventing or ameliorating adverse

  20. Regulation of decoction shugan bushen on testosterone and ACTH in ratswith hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Zhong Pang Fan; Jian Cheng Wu; Xing Zhu; Qian Hong Wan; Ting Zan Li

    2000-01-01

    AIM To observe the regulating effect of decoction shugan bushen (SGBS) on testosterone (Te) andadrenocortiotropin (ACTH).METHODS Fifty wistar male rats divided into four groups randomly, that is, normal group, hepaticfibrosis group, and two Chinese herb medicine treatment groups. The model of toxic hepatic fibrosis wasinduced by 0.5% dimethylnitrosamine (DMN). The decoction SGBS is composed of such herbs as bupleurumRoot. Dodder Seed, curcuma rood indianmulberry etc. According to the different doses of the drugs, ratsare divided into two groups in the treatment groups. The Chinese herb medicine treatment begins in a weekafter the second celiac injection of DMN, lastiong 8 weeks. The rats of normal group and hepatic fibrosisgroup are fed with distilled water once a day. After 11 weeks of Chinese herb medicine treatment, the Teand ACTH were tested insera of rats, and the livers were dissected for the pathology examination.RESULTS The results of pathology examination in rat livers of each group show that the hepatocytes of thenormal group have normal array, no degeneration and fibrosis. Those in the pathology group have obviousdegenerative necrosis and hepatic fibrosis, and in some cases show the evidence of cirrosis. The results intreatment groups are essentially similar to those of normal group. Variance analysis of least significantdifference (LSD) method is employed to compare the hormone level between groups. The serum levels of Teand ACTH in the normal group are 75.30±45.25 ng/dl and 141.02±68.70 ng/L. The levels in hepaticfibrosis group are obviously lower than those of normal group, as 19.77±16.92 ng/dl and 92.85±27.24ng/L, respectivite and with statistically different (P 0.05).Two different doses make no obvious difference between the treatment groups (P>0.05).CONCLUSION SGBS can correct the hormone disturbance and shows the effect of anti-hepatic fibrosis.

  1. Research progress in ectopic ACTH syndrome%异位ACTH综合征研究进展

    Institute of Scientific and Technical Information of China (English)

    宁光

    2006-01-01

    @@ 异位ACTH综合征(EAS)是Cushing综合征的一种特殊类型,是由于垂体以外的肿瘤组织分泌过量有生物活性的促肾上腺皮质激素(ACTH),刺激肾上腺皮质增生,产生过量皮质类固醇引起的临床综合征,占Cushing综合征患者总数的5%~10%.

  2. Clinical features of congenital adrenal insufficiency including growth patterns and significance of ACTH stimulation test.

    Science.gov (United States)

    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 (Pcongenital 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.

  3. Mild Adrenal Steroidogenic Defects and ACTH-Dependent Aldosterone Secretion in High Blood Pressure: Preliminary Evidence

    Directory of Open Access Journals (Sweden)

    João Martin Martins

    2014-01-01

    Full Text Available Introduction. Adrenal glands play a major role in the control of blood pressure and mild defects of steroidogenesis and/or inappropriate control of mineralocorticoid production have been reported in high blood pressure (HBP. Patients and Methods. We used a specific protocol for the evaluation of 100 consecutive patients with inappropriate or recent onset HBP. Specific methods were used to confirm HBP and to diagnose secondary forms of HBP. In addition we tested adrenal steroidogenesis with the common cosyntropin test, modified to include the simultaneous measurement of renin and aldosterone besides 17-hydroxyprogesterone (17OHP and 11-deoxycortisol (S. Results. Secondary forms of HBP were diagnosed in 32 patients, including 14 patients with primary hyperaldosteronism (PA (14% and 10 patients with pheochromocytoma (10%. Mild defects of the 21-hydroxylase (21OHD and 11-hydroxylase (11OHD enzymes were common (42%. ACTH-dependent aldosterone secretion was found in most patients (54% and characteristically in those with mild defects of adrenal steroidogenesis (>60%, PA (>75%, and otherwise in patients with apparent essential HBP (EHBP (32%. Discussion. Mild defects of adrenal steroidogenesis are common in patients with HBP, occurring in almost half of the patients. In those patients as well as in patients with apparent EHBP, aldosterone secretion is commonly dependent on ACTH.

  4. Effects of (+)-8-OH-DPAT on the duration of immobility during the forced swim test and hippocampal cell proliferation in ACTH-treated rats.

    Science.gov (United States)

    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.

  5. Corticotropin (ACTH)-reactive immunoglobulins in adolescents in relation to antisocial behavior and stress-induced cortisol response : The TRAILS study

    NARCIS (Netherlands)

    Schaefer, Johanna M.; Fetissov, Serguei O.; Legrand, Romain; Claeyssens, Sophie; Hoekstra, Pieter J.; Verhulst, Frank C.; Van Oort, Floor V. A.

    2013-01-01

    Elevated levels of corticotropin (ACTH)-reactive immunoglobulins (ACTH IgG) were found in mates 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 studie

  6. A patient with recurrent hypercortisolism after removal of an ACTH-secreting pituitary adenoma due to an adrenal macronodule.

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Ginneken, E.E.M. van; Wesseling, P.; Sweep, C.G.J.; Hermus, A.R.M.M.

    2006-01-01

    A 41-yr-old female was referred for signs and symptoms of Cushing's syndrome. Cortisol was not suppressed by 1 mg dexamethasone (0.41 micromol/l). Midnight cortisol and ACTH were 0.44 micromol/l and 18 pmol/l, respectively. Urinary cortisol excretion was 250 nmol/24 h (normal between 30 and 150 nmol

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

    Science.gov (United States)

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

    Science.gov (United States)

    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.

  9. [Effect of dalargin on the content of endorphins, leucine-enkephalin ACTH and corticosterone of the blood of stressed rats].

    Science.gov (United States)

    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.

  10. The active sequence in the acth molecule responsible for inhibition of the extinction of conditioned avoidance behaviour in rats

    NARCIS (Netherlands)

    Greven, H.M.; Wied, D. de

    1967-01-01

    The effect of structural analogues of the N-terminal decapeptide of ACTH on inhibition of extinction of a conditioned avoidance response in rats has been studied. Studies involving the relation between chain length and behavioural activity revealed that the sequence 4–10 is the shortest peptide whic

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

    Science.gov (United States)

    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.

  12. Burnout and hypocortisolism – a matter of severity? A study on ACTH and cortisol responses to acute psychosocial stress

    Directory of Open Access Journals (Sweden)

    Anna-Karin eLennartsson

    2015-02-01

    Full Text Available Background: Common consequences of long-term psychosocial stress are fatigue and burnout. It has been suggested that burnout could be associated with hypocortisolism, thus, inability to produce sufficient amounts of cortisol. This study aimed to investigate whether patients with clinical burnout exhibit aberrant ACTH and cortisol responses under acute psychosocial stress compared with healthy individuals. Methods: Nineteen patients (9 men and 10 women and 37 healthy subjects (20 men and 17 women, underwent the Trier Social Stress Test. Blood samples and saliva samples were collected before, after and during the stress test for measurements of plasma ACTH, serum cortisol and salivary cortisol. Several statistical analyses were conducted to compare the responses between patients and controls. In addition, in order to investigate the possibility that burnout patients with more severe symptoms would respond differently, sub-groups of patients reporting higher and lower burnout scores were compared. Results: In both patients and healthy controls, we observed elevated levels of ACTH and cortisol after exposure to the stressor. There were no differences in responses of ACTH, serum cortisol or salivary cortisol between patients and controls. Patients reporting higher burnout scores had lower salivary cortisol responses than controls, indicating that patients with more severe burnout symptoms may be suffering from hypocortisolism. In addition patients with more severe burnout symptoms tended to have smaller ACTH responses than the other patients. There was no corresponding difference in serum cortisol however. Conclusion: This study indicates that hypocortisolism is not present in a clinical burnout patient group as a whole but may be present in the patients with more severe burnout symptoms.

  13. Neurotrophic ACTH4-9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis.

    Science.gov (United States)

    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

  14. Optimising glucocorticoid replacement therapy in severely adrenocorticotropin (ACTH) deficient hypopituitary male patients.

    LENUS (Irish Health Repository)

    Behan, Lucy-Ann

    2011-04-18

    Context:  The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15mg to 30mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. Objective:  Primarily to define the hydrocortisone regimen which results in a 24hour cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). Design:  10 male hypopituitary patients with severe ACTH deficiency (basal cortisol <100nM and peak response to stimulation <400nM) were enrolled in a prospective, randomised, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24hour serum cortisol sampling and QoL assessment with the Short Form 36 and the Nottingham Health Profile questionnaires. Free cortisol was calculated using Coolen\\'s equation. All results were compared to those of healthy, matched controls. Results:  CBG was significantly lower across all dose regimens compared to controls (p<0.05). The lower dose regimen C(10mg mane\\/5mg tarde) produced a 24hour free cortisol profile which most closely resembled that of controls. Both regimen A(20mg mane\\/10mg tarde) and B(10mg mane\\/10mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (p<0.001). Conclusions:  The lower dose of HC(10mg\\/5mg) produces a more physiological cortisol profile, without compromising quality of life, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.

  15. Effects of ACTH on RNA synthesis and migration in the adrenal cortex cells of the young rat, as shown by radioautography

    Energy Technology Data Exchange (ETDEWEB)

    Magalhaes, M.C.; Vitor, A.B.; Magalhaes, M.M.

    1986-01-01

    The effect of ACTH on the RNA synthesis in adrenal zona fasciculata cells of the young rat were studied by light and electron microscope radioautography. Two units of ACTH were administered sc to animals and immediately followed by an iv injection of (/sup 3/)uridine. ACTH-injected and control rats, which received the isotope alone, were sacrificed at various time intervals. Labelling over extranucleolar areas was higher in the ACTH-treated animals at 20 min, then becoming lower than in the controls at 60 min and 24 h. Nucleolar radioactivity, however, was consistently decreased by ACTH at all experimental times. Apart from these changes in the rate of synthesis, the over-all curves of labelling were similar to those in the control animals with a striking peak at 1 h. The short-term increase in extranucleolar RNA synthesis observed after ACTH injection was considered to be consistent with the hypothesis that an enhanced extranucleolar synthesis of mRNA takes place early in stimulated animals and is associated with the synthesis of steroidogenic proteins. On the other hand, the relatively decreased uridine uptake of the label by the nucleolus in ACTH-treated animals, suggests an inhibition of nucleolar transcription with diminished pre-rRNA formation in treated animals.

  16. Metabolic effects of cortisol, ACTH, adrenalin and insulin in the marsupial sugar glider, Petaurus breviceps.

    Science.gov (United States)

    Bradley, A J; Stoddart, D M

    1990-11-01

    The effects of cortisol, ACTH, adrenalin and insulin on indices of carbohydrate, fat and protein metabolism were investigated in the conscious marsupial sugar glider Petaurus breviceps. Short-term i.v. infusion of cortisol at dose rates of 0.02, 0.2 and 1.0 mg/kg per h caused the plasma glucose concentration to rise sharply from the normal range of 3.3-4.4 to 8.1-8.7 mmol/l at the end of the infusion period without significant alteration in plasma free fatty acid (FFA), amino acid or urea concentrations. Infusions of ACTH at dose rates of 0.02, 0.06 and 0.45 IU/kg per h caused a similar rise in plasma glucose concentration; however, this was now accompanied by an elevation in plasma FFA concentration, but again without significant changes in either plasma amino acid or urea concentrations. Infusion of adrenalin at 10 micrograms/kg per h caused an increase in the plasma concentrations of both glucose and FFA. Intravenous injections of 0.15 IU insulin/kg caused a rapid and marked decrease in the plasma glucose concentration within 30 min and an increase in the plasma free cortisol concentration. Associated with this change was a marked rise in the plasma concentration of both FFA and free cortisol. The rise in free cortisol was, however, significantly reduced by infusion of glucose. Pretreatment with five daily i.m. injections of 1 mg cortisol acetate/kg, which produced an increase in plasma free cortisol concentration to near the maximum of the physiological range, caused a marked reduction in insulin sensitivity. Cortisol pretreatment caused an increase in the plasma FFA and amino acid concentrations. Petaurus breviceps is highly sensitive to the metabolic effects of glucocorticoids and is similar in this respect to the brush-tailed possum Trichosurus vulpecula. The interactive effects between insulin and glucocorticoids on carbohydrate, fat and protein metabolism in Petaurus breviceps are similar to those shown by Trichosurus vulpecula and some eutherian mammals

  17. Adrenocorticotropin (ACTH) and corticosterone secretion by perifused pituitary and adrenal glands from rodents exposed to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD).

    Science.gov (United States)

    Pitt, J A; Buckalew, A R; House, D E; Abbott, B D

    2000-10-26

    Although in utero maternal stress has been shown to have lasting effects on rodent offspring, fetal effects of chemically-induced alterations of the maternal hypothalamic-pituitary-adrenal axis (HPA) have not been well studied. This study examined the effects of in vivo 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on pituitary-adrenal function in the male rat, pregnant female rat and pregnant female mouse. The secretion of adrenocorticotropin (ACTH) and corticosterone (CORT) in pituitary and adrenal glands, respectively, was assessed in ex vivo perifusion cultures. Male and pregnant female (gestation day 8) Sprague-Dawley rats were gavaged once with 10 microgram/kg TCDD, pregnant female mice once with 24 microgram/kg TCDD, and euthanized 10 days later. Hemi-pituitary (rat) or whole anterior pituitaries (mice) and right adrenal glands from the same animal were quartered, perifused under baseline and stimulated conditions. In both males and pregnant females, TCDD did not affect corticotropin releasing hormone (CRH)-stimulated ACTH secretion. Neither total pituitary ACTH nor plasma ACTH was altered in either sex or species by TCDD treatment. ACTH-stimulated CORT secretion was not affected by TCDD in either sex or species, and adrenal tissue and plasma CORT levels were unchanged in males and pregnant females by TCDD. However, the plasma ACTH:CORT ratio was decreased about 46% in male rats treated with TCDD. Plasma CORT levels were 23-fold higher and plasma ACTH levels were 1.5-fold higher in pregnant females than in male rats. In male versus female rats, adrenal CORT and anterior pituitary ACTH tissue levels were about 7.5- and 1.75-fold higher and ACTH, respectively. Female mouse adrenal tissue CORT was about 4-fold greater than female rat. The reduced plasma ACTH:CORT ratio in the male rat suggests that TCDD disturbs HPA function. Exposure of male rat to a 5-fold higher dose in earlier studies clearly demonstrated effects of TCDD on male rat HPA. The present

  18. Ultrastructural, histochemical, and biochemical studies of two cases with amylase, ACTH, and beta-MSH producing tumor.

    Science.gov (United States)

    Gomi, K; Kameya, T; Tsumuraya, M; Shimosato, Y; Zeze, F; Abe, K; Yoneyama, T

    1976-10-01

    Two cases of intrathoracic tumor, different in histology and accompanied by hyperamylasemia, were studied ultrastructurally, histochemically, and biochemically. The ultrastructure of the tumor cell cytoplasm showed many zymogen granules in case 1 and smaller cored granules in addition to zymogen granules in case 2. Both tumors contained not only a large amount of amylase, which was electrophoretically of saliva type with three components, but also significant amounts of immunoreactive ACTH and beta-MSH. Starch film and immunofluorescence showed that the tumor cells stored amylase. It was concluded from these findings that the tumor cells ectopically producing amylase, which showed differentiation toward the cells with zymogen production, could differentiate toward the cells of ACTH-MSH system at the same time.

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

    Science.gov (United States)

    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.

  20. Pre- and postnatally administered ACTH, Organon 2766 and CRF facilitate or inhibit active avoidance task performance in young adult mice.

    Science.gov (United States)

    Honour, L C; White, M H

    1988-01-01

    This study investigated the effect of learning/memory-related neuropeptides on behavioral task performance in later life. A 1 mg/kg dosage of adrenocorticotropic hormone 4-9, Organon 2766, ACTH/MSH 4-10, ACTH 1-24, CRF, or diluent was subcutaneously injected into either pregnant females or into newborn pups during specific neural developmental windows. Each of the progeny was trained in an active-avoidance task and tested for acquisition on postpartum days 35-37. The mice were then tested for memory task performance and reacquisition on days 42-44 postpartum using the identical experimental paradigm as that used in the training sessions. Prenatal treatment with these memory-related neuropeptides resulted in significant facilitation of learning/memory task performance in male and female mice treated with Organon 2766 (p less than 0.001), and a significant inhibition of learning/memory task performance in males and females treated with ACTH 1-24 (p less than 0.01). Additional sex-specific performance facilitations and inhibitions resulted from the pre- or postnatal administration of the various neuropeptides used in this study. These results suggest that neuropeptides, when available in increased amounts during specific neural developmental windows, can significantly improve or suppress related behavioral performance capability in later life.

  1. Adrenocortical steroid response to ACTH in different phenotypes of non-obese polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Cinar Nese

    2012-12-01

    Full Text Available Abstract 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  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.

  2. Short- and long-term effects of ACTH on the adrenal zona glomerulosa of the rat. A coupled stereological and enzymological study.

    Science.gov (United States)

    Mazzocchi, G; Malendowicz, L K; Rebuffat, P; Robba, C; Gottardo, G; Nussdorfer, G G

    1986-01-01

    Short-term ACTH treatment provoked a decrease in volume of the lipid-droplet compartment in rat zona glomerulosa cells, and a rise in plasma and intracellular concentrations of corticosterone and aldosterone. It enhanced activities of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), 11 beta-hydroxylase (11 beta OH) and 18-hydroxylase (18OH). Long-term ACTH administration produced a hypertrophy of the zona glomerulosa and its parenchymal cells, a result of the increase in volume of the smooth endoplasmic reticulum and the mitochondrial compartment. The surface area per cell of mitochondrial inner membranes increased; the tubular cristae were transformed into a homogeneous population of vesicles. The plasma and intracellular concentrations of corticosterone further increased, whereas those of aldosterone fell below basal levels (the "aldosterone-escape" phenomenon). The activities of 3 beta HSD and 11 beta OH were enhanced, that of 180H decreased. Therefore, ACTH stimulates zona glomerulosa growth and transforms parenchymal elements into zona fasciculata cell-types. Cyanoketone nullified acute ACTH effects on plasma and intracellular concentrations of corticosterone and aldosterone, but did not affect the activities of 11 beta OH and 18OH. Chronic ACTH treatment produced similar results, although 18OH activity was not suppressed. The mechanism underlying the "aldosterone-escape" phenomenon may thus involve a rise in the intracellular concentration of corticosterone, caused by the enhanced synthesis and activation of 3 beta HSD and 11 beta OH.

  3. Ovarian localization of 11β-hydroxysteroid dehydrogenase (11βHSD): effects of ACTH stimulation and its relationship with bovine cystic ovarian disease.

    Science.gov (United States)

    Amweg, A N; Salvetti, N R; Stangaferro, M L; Paredes, A H; Lara, H H; Rodríguez, F M; Ortega, H H

    2013-10-01

    Cystic ovarian disease (COD) is an important cause of infertility in cattle, and ACTH has been involved in regulatory mechanisms related to ovarian function associated with ovulation, steroidogenesis, and luteal function. Here, we examined the localization of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 11βHSD2 proteins in the ovary of healthy cows and animals with spontaneous and ACTH-induced COD and the in vitro response of the follicular wall exposed to ACTH. After stimulation by ACTH, we documented changes in 11βHSD expression and cortisol secretion by the follicular wall of large antral and follicular cysts. Follicular cysts showed a higher constitutive expression of both enzymes, whereas ACTH induced an increase in 11βHSD1 in tertiary follicles and follicular cysts and a decrease in 11βHSD2 in follicular cysts. Moderate expression of 11βHSD1 was observed by immunohistochemistry in granulosa of control animals, with an increase (P cortisol in COD pathogenesis and in regulatory mechanisms of ovarian function.

  4. Using the human melanocortin-2 receptor as a model for analyzing hormone/receptor interactions between a mammalian MC2 receptor and ACTH(1-24).

    Science.gov (United States)

    Liang, Liang; Angleson, Joseph K; Dores, Robert M

    2013-01-15

    When considering the interactions between the melanocortin peptides (i.e., ACTH, α-MSH, β-MSH, γ-MSH) and the melanocortin receptors (i.e., MC1R, MC2R, MC3R, MC4R, MC5R), it appears that the structure/function relationship between ACTH and MC2R is the most complicated. Human ACTH(1-24) and the human melanocortin-2 receptor provide a useful model system for understanding how ACTH emerged as the sole ligand for the melanocortin-2 receptor of bony vertebrates. This review will discuss how studies utilizing analogs of hACTH(1-24) have revealed two critical amino acid motifs in this ligand (HFRW and KKRRP) which are required for activation of the melanocortin-2 receptor. In addition, observations on the unique activation features of the melanocortin-2 receptor, as revealed from studies on Familial Glucocorticoid Deficiency, will be considered. Finally, the evolutionary implications of the relationship between MC2R and MRAP1 will be discussed.

  5. Spectrum of Adrenal Dysfunction in Patients with Acquired Immunodeficiency Syndrome Evaluation of Adrenal and Pituitary Reserve with ACTH and Corticotropin-Releasing Hormone Testing.

    Science.gov (United States)

    Freda, P U; Papadopoulos, A D; Wardlaw, S L; Goland, R S

    1997-07-01

    Patients with acquired immunodeficiency syndrome (AIDS) have been reported to develop abnormalities of the endocrine system and in particular of the hypothalamic-pituitary-adrenal (HPA) axis. To define the abnormalities of HPA function in AIDS patients better, we performed ACTH and ovine corticotropin-releasing hormone (oCRH) testing in a group of AIDS patients and oCRH testing in a group of healthy subjects. Our study found that in AIDS patients with normal ACTH testing, oCRH testing revealed a variety of subclinical abnormalities of ACTH and cortisol responses. Although we did not find frank adrenal insufficiency in any of these AIDS patients, it remains to be determined if any of the subclinical abnormalities we identified are predictive of clinically significant adrenal insufficiency; it may be that as AIDS patients live longer, the subclinical abnormalities will progress to adrenal insufficiency. (Trends Endocrinol Metab 1997;8:173-180). (c) 1997, Elsevier Science Inc.

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

    Science.gov (United States)

    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 (P0.05). 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

  7. Hypothermic and antipyretic effects of ACTH (1-24) and alpha-melanotropin in guinea-pigs

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Jankowski, M.D.; Wittwer, D.J.; Heisey, D.M.; Franson, J.C.; Hofmeister, E.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.

  9. Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test

    Science.gov (United States)

    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

  10. Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test

    Directory of Open Access Journals (Sweden)

    René Rodríguez-Gutiérrez

    2016-01-01

    Full Text Available 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

  11. Lower birth weight and attenuated adrenocortical response to ACTH in offspring from sows that orally received cortisol during gestation.

    Science.gov (United States)

    Kranendonk, Godelieve; Hopster, Hans; Fillerup, Maaike; Ekkel, E Dinand; Mulder, Eduard J H; Wiegant, Victor M; Taverne, Marcel A M

    2006-03-01

    Prenatal stress is known to affect several offspring characteristics, but its effects depend among other factors on the period of gestation in which it is applied. In the present study, oral administration of hydrocortisone-acetate (HCA) was used to elevate cortisol concentrations in pregnant sows to levels also observed after psychological stress. HCA was administered during three different periods of gestation (115 days in pigs): period 1: 21-50 (P1, n = 10), period 2: 51-80 (P2, n = 10) and period 3: 81-110 (P3, n = 10) days after insemination. Control sows (n = 11) received vehicle from 21-110 days after insemination. When P1-, P2- and P3-sows did not receive HCA, they also received vehicle. During gestation, weekly saliva samples were taken from the sows to determine salivary cortisol concentrations. Treatment effects on sow, litter and piglet characteristics were determined. In addition, two female piglets per litter were subjected to an ACTH-challenge test at 6 weeks of age to determine the adrenocortical response to ACTH. Pigs were slaughtered at 6 months of age and slaughter weight, back fat thickness and percentage of lean meat were analysed. During the period of treatment with HCA, salivary cortisol concentrations were increased in P1-, P2- and P3-sows compared to control sows (P 0.30), but pooled HCA-litters had a higher percentage of live born piglets (P Gestation length did not differ among treatment groups (P = 0.21), but did affect treatment effects on birth weight. Overall, HCA-piglets weighed less at birth, and remained lighter until weaning (P < 0.05). The salivary cortisol concentrations after i.m. injection of ACTH (2.5 IU/kg) were lower in P1- and P3-piglets compared to control piglets. At slaughter, HCA-treatment indirectly decreased lean meat percentage and increased back fat thickness. In conclusion, elevated peripheral cortisol concentrations in pregnant sows affect both litter characteristics and piglet physiology, the latter depending on

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

    Directory of Open Access Journals (Sweden)

    Valeria de Miguel

    2010-06-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  14. An ectopic ACTH-producing small cell lung carcinoma associated with enhanced corticosteroid biosynthesis in the peritumoral areas of adrenal metastasis.

    Science.gov (United States)

    Satoh, Hironori; Saito, Ryoko; Hisata, Shu; Shiihara, Jun; Taniuchi, Shinji; Nakamura, Yasuhiro; Nukiwa, Toshihiro; Ebina, Masahito; Sasano, Hironobu

    2012-06-01

    A 60-year-old Japanese male presented with swelling of bilateral cervical lymph nodes was subsequently diagnosed as the late stage of primary small cell lung carcinoma (SCLC). He was then treated with cisplatin and irinotecan as first-line chemotherapy, but hypokalemia with muscle weakness of the bilateral legs became gradually noticeable following two months of effective chemotherapy. A computed tomography (CT) scan revealed enlargement of bilateral adrenal glands and abdominal and mediastinal lymph nodes, though primary lung tumor remained the same in size. An ectopic ACTH-producing syndrome (EAS) was subsequently revealed by the following endocrinological studies. Hypokalemia was clinically improved by the treatment with metyrapone and the second-line chemotherapy with amrubicin for SCLC was started, but the patient died 12 days after the second-line chemotherapy. Post-mortem examination revealed ACTH immunoreactivity in tumor cells of all the metastatic lesions. Non-neoplastic adrenal cortex demonstrated hyperplasia associated with lipid depletion and marked expression of steroidogenic enzymes, especially in cortical cells around tumor infiltration, suggestive of paracrine ACTH stimulation of cortisol production. This is the first report evaluating expression of steroidogenic enzymes in adrenal cortex especially adjacent to the adrenal metastasis in the patients with EAS due to SCLC. These findings suggest that ACTH producing adrenal metastasis can induce EAS more frequently and severely, and that the symptoms and examination of EAS should be monitored carefully in the patients with adrenal metastasis of SCLC.

  15. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P;

    1988-01-01

    Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...

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

    Science.gov (United States)

    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...

  17. Using microarrays to identify positional candidate genes for QTL: the case study of ACTH response in pigs

    DEFF Research Database (Denmark)

    Jouffe, Vincent; Rowe, Suzanne; Liaubet, Laurence

    2009-01-01

    a case study where we explore ways to integrate QTL data and microarray data for the pig, which has only a partial genome sequence. We outline various procedures to localize differentially expressed genes on the pig genome and link this with information on published QTL. The starting point is a set...... of 237 differentially expressed cDNA clones in adrenal tissue from two pig breeds, before and after treatment with adrenocorticotropic hormone (ACTH) Microarray studies can supplement QTL studies by suggesting potential candidate genes in the QTL regions, which by themselves are too large to provide...... a limited selection of candidate genes. Here we provide a case study where we explore ways to integrate QTL data and microarray data for the pig, which has only a partial genome sequence. We outline various procedures to localize differentially expressed genes on the pig genome and link...

  18. A Novel Medical Treatment of Cushing's Due to Ectopic ACTH in a Patient With Neurofibromatosis Type 1.

    Science.gov (United States)

    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 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.

  19. Lycopene and beta-carotene induce growth inhibition and proapoptotic effects on ACTH-secreting pituitary adenoma cells.

    Directory of Open Access Journals (Sweden)

    Natália F Haddad

    Full Text Available Pituitary adenomas comprise approximately 10-15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27(kip1 in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2 and increased expression of p27(kip1 in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27(kip1; and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing's disease.

  20. Resposta do ACTH plasmático ao estímulo com CRH ou CRH + desmopressina em pacientes com síndrome de Cushing ACTH- dependente submetidos a cateterismo bilateral simultâneo dos seios petrosos inferiores Response of plasmatic ACTH to CRH or combined CRH/desmopressin stimulation in patients with ACTHdependent Cushing's syndrome submitted to simultaneous bilateral petrosal sinuses sampling

    Directory of Open Access Journals (Sweden)

    Daniella Maria Carneiro do Rêgo

    2007-12-01

    Full Text Available OBJETIVO: Comparar a resposta do ACTH plasmático após estímulo com CRH ou CRH + desmopressina em pacientes com síndrome de Cushing ACTH-dependente que realizaram cateterismo bilateral simultâneo dos seios petrosos inferiores. MATERIAIS E MÉTODOS: O procedimento foi realizado em 21 pacientes - 14 mulheres e 7 homens - com síndrome de Cushing ACTH-dependente no período de janeiro de 1998 a dezembro de 2003. Após a cateterização de ambos os seios petrosos, amostras de sangue para ACTH foram colhidas, simultaneamente, nos seios petrosos e veia periférica, tanto no estado basal como após três e cinco minutos da administração de CRH humano (100 mg (6 pacientes ou CRH + desmopressina (100 mg + 10 mg (15 pacientes. RESULTADOS: Aos três minutos, houve aumento percentual do ACTH tanto no grupo CRH (257,77 ± 240,36 no seio petroso direito e 718,78 ± 1.358,82 no seio petroso esquerdo [média ± desvio-padrão] como no grupo CRH + desmopressina (1.263,35 ± 1.842,91 no seio petroso direito [p = 0,06] e 583,93 ± 1.020,03 no seio petroso esquerdo [p = 0,83]. Aos cinco minutos houve declínio percentual do ACTH no grupo do CRH (181,07 ± 217,39 no seio petroso direito e 188,25 ± 270,15 no seio petroso esquerdo e aumento progressivo no grupo do CRH + desmopressina (1.365,29 ± 1.832,31 no seio petroso direito [p = 0,03] e 866,43 ± 1.431,72 no seio petroso esquerdo [p = 0,11]. Nos três pacientes com secreção ectópica não houve gradiente. CONCLUSÃO: A estimulação combinada CRH + desmopressina induziu maior produção de ACTH em adenomas corticotróficos em comparação ao CRH, o que pode melhorar a sensibilidade diagnóstica deste procedimento.OBJECTIVE: To compare the responses of plasmatic ACTH to CRH or combined CRH/desmopressin stimulation in patients with ACTH-dependent Cushing's syndrome submitted to simultaneous, bilateral inferior petrosal sinuses sampling. MATERIALS AND METHODS: The procedure was performed in 21 patients - 14

  1. 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.

    Science.gov (United States)

    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.

  2. Blunted ACTH and cortisol responses to systemic injection of corticotropin-releasing hormone (CRH) in fibromyalgia: role of somatostatin and CRH-binding protein.

    Science.gov (United States)

    Riedel, Walter; Schlapp, Ulrike; Leck, Stefanie; Netter, Petra; Neeck, Gunther

    2002-06-01

    Thirteen female patients suffering from fibromyalgia (FM) and thirteen female age-matched controls were intravenously injected with a bolus dose of 100 microg corticotropin-releasing hormone (CRH), and the evoked secretion pattern of ACTH, cortisol, somatostatin, and growth hormone (GH) was followed up for two hours, together with the plasma levels of CRH. The increases of ACTH and cortisol following CRH were not significantly different between controls and FM patients. The increase of plasma CRH following its injection was significantly higher in FM patients and lasted about 45 min, paralleled by an increase of somatostatin with a similar time course. Basal GH levels were significantly lower in FM patients. GH increased in FM patients 90 min after injection of CRH, coincident with decreasing CRH and somatostatin levels, while GH levels in controls rather decreased with the lowest values occurring 90 min after CRH. The results support the concept that the hormonal secretion pattern frequently observed in FM patients is primarily caused by CRH, possibly as a response to chronic pain and stress. The elevated levels of CRH in the circulation of FM patients suggest elevated levels of CRH-binding protein, which could explain why the levels of ACTH and cortisol between controls and FM following CRH do not differ.

  3. Effect of dopamine, dopamine D-1 and D-2 receptor modulation on ACTH and cortisol levels in normal men and women

    DEFF Research Database (Denmark)

    Boesgaard, S; Hagen, C; Andersen, A N;

    1990-01-01

    The regulation of the hypothalamic-pituitary-adrenal axis by dopamine is not fully understood. Therefore, we have studied the effect of dopamine, metoclopramide, a D-2 receptor antagonist, and fenoldopam, a specific D-1 receptor agonist, on ACTH and cortisol levels in normal subjects. Normal women...... received 5-h infusions of either glucose (N = 6) or dopamine at rates of 0.04 (N = 6), 0.4 (N = 6) and 4.0 micrograms.kg-1.min-1 (N = 8). After 3 h, 10 mg metoclopramide was given iv. No intergroup differences regarding ACTH and cortisol levels were observed (p greater than 0.05). In a second study six...... women received dopamine (4.0 micrograms.kg-1.min-1) or glucose for 18 h. During the infusions cortisol and ACTH levels were similar on the two study days. Administration of metoclopramide (10 mg) after 17 h induced a significant increase in cortisol levels during dopamine infusion (p less than 0...

  4. Persistent hypokalemia after successful adrenalectomy in a patient with Cushing's syndrome due to ectopic ACTH secretion: possible role of 11beta-hydroxysteroid dehydrogenase inhibition.

    Science.gov (United States)

    Arteaga, E; Fardella, C; Campusano, C; Cárdenas, I; Martinez, P

    1999-12-01

    Ectopic ACTH secretion is characterized by a high incidence of hypokalemia. The pathophysiology of hypokalemia has not been totally clarified, although it has been postulated that excessive amounts of adrenal steroids may play a role, as well as a possible role of the inhibition of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD). This enzyme normally converts cortisol to cortisone avoiding the mineralocorticoid action of cortisol. We present a patient with ectopic ACTH secretion due to a metastatic carcinoid tumor. The clinical picture was characterized by maintained hypokalemia (1.4 mmol/l) resistant to potassium, spironolactone and ketoconazole administration. A bilateral adrenalectomy was performed but the hypokalemia persisted while he was receiving a physiological dose of cortisol. Eight days after adrenalectomy cortisol was replaced by an equivalent dose of dexamethasone. This change was followed by a rapid and persistent normalization of hypokalemia suggesting a mineralocorticoid effect of cortisol. In conclusion, the origin of hypokalemia in our patient with ectopic ACTH secretion was secondary to cortisol. We postulate that this peculiar effect of cortisol could have happened if an inhibition of 11beta-OHSD occurred.

  5. Analysis of glucose dysbolism in patients with ectopic ACTH syndrome%异位ACTH综合征患者糖代谢异常的特点分析

    Institute of Scientific and Technical Information of China (English)

    赵蕾; 母义明; 窦京涛; 陆菊明; 潘长玉

    2008-01-01

    通过对经病理证实的117例库欣综合征患者临床资料的分析,探讨异位ACTH综合征(EAS)糖代谢异常的特点.117例患者分为3组:EAS组9例,库欣病组(CD)67例,肾上腺皮质腺瘤组(AA)41例.与CD组和AA组相比,EAS组继发性糖尿病发生率高,血糖水平高,HbAlc水平低,原发病灶根治术后,血糖降至正常.%The characteristics of glucose dysbolism in ectopic ACTH syndrome (EAS) were investigated by analysing the clinical data of 117 patients with Cushing syndrome (CS). The patients with CS were divided into 3 groups : EAS group (n = 9) , Cushing's disease (CD) group (n = 67) and adrenocortical adenoma (AA) group (n =41). Retrospective analysis of the data covered the prevalence of secondary diabetes, blood glucose, HbAlc, blood potassium, and blood ACTH and 24 h urinary-free cortisol (UFC) levels. Compared with CD and AA groups, the prevalence of secondary diabetes and blood glucose level were higher in EAS group, while HbAlc level was lower. Blood glucose level in patients with ectopic ACTH syndrome decreased to normal after tumor removal.

  6. Unilateral adrenalectomy can be an alternative therapy for infantile onset Cushing' s syndrome caused by ACTH-independent macronodular adrenal hyperplasia with McCune-Albright syndrome.

    Science.gov (United States)

    Hamajima, Takashi; Maruwaka, Kaori; Homma, Keiko; Matsuo, Kumihiro; Fujieda, Kenji; Hasegawa, Tomonobu

    2010-01-01

    We report herein the case of a 1-year-old boy with McCune-Albright syndrome (MAS) who presented with infantile-onset Cushing' s syndrome caused by ACTH independent macronodular adrenal hyperplasia (AIMAH). Abdominal CT, MRI, and adrenal scintigraphy with (131)I-adosterol identified bilateral adrenal involvement with the left adrenal gland being larger and functionally more active. Unilateral adrenalectomy of the left gland was performed and ameliorated many clinical symptoms, such as Cushingoid appearance and height restriction, and it also normalized many endocrinological data, such as diurnal rhythms of ACTH and cortisol, ACTH and cortisol responses to CRH, and urinary 24 hr free cortisol. Glucocorticoid was replaced for the first 1 year and 6 months after the operation. One adrenal crisis episode occurred at 3 weeks after the operation, but none have occurred since. These results suggest that unilateral adrenalectomy of the larger gland can be an alternative therapy for infantile onset Cushing' s syndrome caused by AIMAH with MAS, when asymmetric involvement is evident and the smaller gland is not markedly enlarged.

  7. Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents.

    Science.gov (United States)

    Eremin, Kirill O; Kudrin, Vladimir S; Saransaari, Pirjo; Oja, Simo S; Grivennikov, Igor A; Myasoedov, Nikolay F; Rayevsky, Kirill S

    2005-12-01

    Corticotrophin (ACTH) and its analogues, particularly Semax (Met-Glu-His-Phe-Pro-Gly-Pro), demonstrate nootropic activity. Close functional and anatomical links have been established between melanocortinergic and monoaminergic brain systems. The aim of present work was to investigate the effects of Semax on neurochemical parameters of dopaminergic- and serotonergic systems in rodents. The tissue content of 5-hydroxyindoleacetic acid (5-HIAA) in the striatum was significantly increased (+25%) 2 h after Semax administration. The extracellular striatal level of 5-HIAA gradually increased up to 180% within 1-4 h after Semax (0.15 mg/kg, ip) administration. This peptide alone failed to alter the tissue and extracellular concentrations of dopamine and its metabolites. Semax injected 20 min prior D: -amphetamine dramatically enhanced the effects of the latter on the extracellular level of dopamine and on the locomotor activity of animals. Our results reveal the positive modulatory effect of Semax on the striatal serotonergic system and the ability of Semax to enhance both the striatal release of dopamine and locomotor behavior elicited by D-amphetamine.

  8. Cerebrospinal fluid rhinorrhea as a complication of ACTH-secreting pituitary macroadenoma in a patient with morbid obesity

    Directory of Open Access Journals (Sweden)

    Dar'ya Viktorovna Petrova

    2014-11-01

    Full Text Available Cushing's disease (CD is a progressive neuroendocrine disease caused by a pituitary tumor producing excessive amounts of ACTH. In most cases (80-85% the cause of the disease is a pituitary corticotroph microadenomas (located within the sella, measuring 3–10 mm, rarely multiple microadenomas and only 15% of cases are presented as corticotroph hyperplasia or pituitary macroadenoma extending beyond the sella. The macroadenomas in CD usually extend suprasellar (10%, infrasellar tumor growth is relatively rare (5%. If the clinical picture is subtle, the symptoms are caused by the development "mass effect" of the tumor as it propagates to the surrounding pituitary structures. Suprasellar growth leads to compression of the optic chiasm with narrowing of visual fields, infrasellar growth destructs the bottom of the sella turcica and may cause nasal cerebrospinal fluid leak, which is dangerous due depressurization of the cranial cavity and its communication with environmental pathogens, development of life-threatening conditions such as meningitis, meningoencephalitis, ventriculitis. Leading life-threatening complications of the CD are infectious and cardiovascular. But in the case of nasal liquorrhea with expansion of the tumor in sphenoid sinus with destruction of the bottom of the sella, there is an immediate threat to the life of the patient. This article presents an example of a patient with morbid obesity and lack of specific clinical manifestations of CD, in whom the diagnosis of disease CD was made on the results of laboratory and instrumental examination, which experienced a spontaneous nasal cerebrospinal fluid leak.

  9. Contagem de células somáticas e produção leiteira em cabras Saanen estressadas via aplicação de ACTH Somatic cell count and milk production of Saanen goats stressed via application of ACTH

    Directory of Open Access Journals (Sweden)

    Ana Paula Rodrigues Gaiato

    2012-05-01

    Full Text Available Avaliou-se neste estudo o efeito do estresse, via administração de ACTH (hormônio adrenocorticotrófico, sobre a quantidade e qualidade do leite produzido e a indicação de estresse pela alteração no nível de cortisol. Assim, 12 cabras lactantes foram distribuídas em dois grupos: seis animais receberam aplicação de 0,06 UI de ACTH/kg de PV (desafiadas e seis receberam solução placebo (controle, todas via intravenosa. O desafio ocorreu ao longo da lactação, com aplicação do protocolo aos 30, 60, 120 e 180 dias do início da lactação, avaliando-se em cada data os níveis de cortisol 30 minutos antes, no ato da aplicação, 60, 120 e 300 minutos depois. A produção leiteira foi mensurada diariamente durante 270 dias e, a cada 20 dias, o leite foi colhido para contagem de células somáticas (CCS pelo método direto. Os teores de cortisol mensurados em -30 e 0 minuto antes da aplicação de ACTH foram baixos e semelhantes entre os grupos. Entretanto, a partir de 60 minutos, constatou-se efeito da aplicação de ACTH, com teor de cortisol de 61,37±6,65 versus 5,47±1,21 ng/mL e de 51,17±10,21 versus 4,67±1,21 ng/mL aos 120 minutos. Aos 300 minutos, o cortisol retornou ao nível basal. Não houve diferença na produção de leite, no teor de proteína e de gordura do leite, cujos valores nos grupos ACTH e Placebo foram 1,37±0,59 e 1,38±0,63 kg de leite, respectivamente. A contagem de células somáticas não foi influenciada pelo estresse e apresentou valores situados na faixa indicada para animais sadios. Constatou-se estresse pontual em decorrência da aplicação de ACTH, porém sem alterações de natureza quantitativa e qualitativa do leite produzido, e isso indica que atividades de manejo que estressam os animais pontualmente não trazem prejuízos ao sistema produtivo.The objective of this study was to analyze the stress effect, via administration of ACTH (adrenocorticotropic hormone, on quantity and quality of milk

  10. An influence of mental stress, related to parachute jumping, on ACTH and cortizol hormones concentration in blood serum [Wpływ stresu związanego ze skokami spadochronowymi na stężenie ACTH i kortyzolu w surowicy krwi

    Directory of Open Access Journals (Sweden)

    Kowalczyk, Edward

    2012-10-01

    Full Text Available Aim. The purpose of this research was to estimate an influence of parachute jumps on the level of ACTH and cortizol hormones among professional soldiers from air-borne forces. Methods. The investigation was carried out on 46 professional soldiers from 16 Air-Borne Battalion, patients of the outpatient department – SPZOZ JW. 4495, men at 20 to 45 age, healthy – admitted to parachute jumping in air-borne forces. They were divided into groups according to their knowledge and an experience in parachuting. Venous blood samples were taken to examine the level of ACTH and cortizol hormones three times during experiment: on a free day, day of parachute jumping and 24hrs after jump. Additionally in order to estimate the level of nervous tension and mental stress, in every stage of the experiment, personal questionnaires in accordance with STAI were carried out. Results. The results show the influence of psychological stress related to parachute jumps on the level of ACTH and cortizol hormones depending on experience in parachuting.

  11. ACTH (Adrenocorticotropic Hormone) Test

    Science.gov (United States)

    ... the arms and legs Fat collection between the shoulders Rounded, red face Fragile and thin skin Purple lines on the abdomen Muscle weakness Acne Skin infections Increased body hair Fatigue These ...

  12. Aberrant expression of glucagon receptors in adrenal glands of a patient with Cushing's syndrome and ACTH-independent macronodular adrenal hyperplasia Expresion aberrante de receptores de glucagón en tejido adrenal de un paciente con síndrome de Cushing e hiperplasia adrenal macronodular indedependiente de ACTH

    Directory of Open Access Journals (Sweden)

    Valeria de Miguel

    2010-06-01

    Full Text Available 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.La hiperplasia adrenal macronodular bilateral independiente de ACTH (HAMIA es una causa infrecuente de Síndrome de Cushing, caracterizada por lesiones adrenales bilaterales, hipercortisolismo y ACTH plasmática suprimida. La síntesis de cortisol estaría regulada a través de ligandos de receptores asociados a proteína G que se expresan en forma aberrante en la corteza de las glándulas adrenales. El objetivo de este trabajo es analizar

  13. ACTH-independent macronodular adrenocortical hyperplasia reveals prevalent aberrant in vivo and in vitro responses to hormonal stimuli and coupling of arginine-vasopressin type 1a receptor to 11 beta-hydroxylase

    NARCIS (Netherlands)

    Hofland, Johannes; Hofland, Leo J.; van Koetsveld, Peter M.; Steenbergen, Jacobie; de Herder, Wouter W.; van Eijck, Casper H.; de Krijger, Ronald R.; van Nederveen, Francien H.; van Aken, Maarten O.; de Groot, Johannes W.; Links, Thera P.; de Jong, Frank H.; Feelders, Richard A.

    2013-01-01

    Background: Adrenal Cushing's syndrome caused by ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) can be accompanied by aberrant responses to hormonal stimuli. We investigated the prevalence of adrenocortical reactions to these stimuli in a large cohort of AIMAH patients, both in viv

  14. An influence of mental stress, related to parachute jumping, on ACTH and cortizol hormones concentration in blood serum [Wpływ stresu związanego ze skokami spadochronowymi na stężenie ACTH i kortyzolu w surowicy krwi

    OpenAIRE

    Kowalczyk, Edward; Kura, Marcin

    2012-01-01

    Aim. The purpose of this research was to estimate an influence of parachute jumps on the level of ACTH and cortizol hormones among professional soldiers from air-borne forces. Methods. The investigation was carried out on 46 professional soldiers from 16 Air-Borne Battalion, patients of the outpatient department – SPZOZ JW. 4495, men at 20 to 45 age, healthy – admitted to parachute jumping in air-borne forces. They were divided into groups according to their knowledge and an experience in par...

  15. Síndrome de Guillain-Barré: a propósito de 5 casos tratados com ACTH e cortisona

    Directory of Open Access Journals (Sweden)

    José Lamartine de Assis

    1953-12-01

    Full Text Available São registrados 5. casos de síndrome de Guillain-Barré (polirradiculoneurite tratados com ACTH ou cortisona. Foi observada melhora rápida em todos êles, em tempo variável de um para outro caso, mas menor que o tempo médio de evolução da moléstia quando tais hormônios não são empregados. Em vista da evolução observada é discutida a teoria da patogenia alérgica da doença e sua inclusão no grupo das doenças desmielinizantes do sistema nervoso.

  16. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P;

    1988-01-01

    determined within 4-8 weeks. The results indicate that serum CK-BB and NSE are potential markers for SCC at the time of diagnosis and that changes in the concentrations during the first course of cytostatic therapy are promising as biochemical tests for early detection of response to chemotherapy.......Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...... stage patients and 71% in limited stage patients. Frequent initial monitoring of the substances showed an increase in the concentrations of pretherapeutic elevated CK-BB and NSE on day 1 or 2 followed by a sharp decrease within 1 week. These changes were correlated to objective clinical response...

  17. An unusual case of an ACTH-secreting macroadenoma with a germline variant in the aryl hydrocarbon receptor-interacting protein (AIP) gene

    DEFF Research Database (Denmark)

    Dinesen, Pia T; Dal, Jakob; Gabrovska, Plamena;

    2015-01-01

    was diagnosed with a large pituitary tumor by magnetic resonance imaging (MRI). His visual fields were intact and he exhibited no features of CD. Owing to an exuberant response to synacthen, an overnight dexamethasone suppression test was performed revealing inadequate suppression of plasma cortisol (419 nmol...... test demonstrated high basal and stimulated cortisol levels; an overnight dexamethasone suppression test showed no suppression (791 nmol/l) and elevated plasma ACTH levels (135 ng/l). A transcranial operation was performed followed by radiotherapy. Two months after radiotherapy, he developed secondary...... growth rather than symptoms of hypersecretion. The particular AIP gene variant identified in our patient is shared by four other reported cases of CD. Future studies are needed to assess whether the reported AIP gene variant is more than just coincidental. LEARNING POINTS: CD is occasionally dominated...

  18. ACTH-producing carcinoma of the pituitary with refractory Cushing's Disease and hepatic metastases: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Sippel Rebecca

    2009-04-01

    Full Text Available Abstract Background Pituitary carcinomas are rare neuroendocrine tumors affecting the adenohypophysis. The hallmark of these lesions is the demonstration of distant metastatic spread. To date, few well-documented cases have been reported in the literature. Case presentation Here, we report the case of a fatal pituitary carcinoma evolving within two years from an adrenocorticotrophic hormone (ACTH-secreting macroadenoma and review the global literature regarding this rare neuroendocrine tumor. Conclusion Pituitary carcinomas are extremely rare neoplasms, representing only 0.1% to 0.2% of all pituitary tumors. To date, little is understood about the molecular basis of malignant transformation. The latency period between initial presentation of a pituitary adenoma and the development of distal metastases marking carcinoma is extremely variable, and some patients may live well over 10 years with pituitary carcinoma.

  19. Cerebellin and des-cerebellin exert ACTH-like effects on corticosterone secretion and the intracellular signaling pathway gene expression in cultured rat adrenocortical cells--DNA microarray and QPCR studies.

    Science.gov (United States)

    Rucinski, Marcin; Ziolkowska, Agnieszka; Szyszka, Marta; Malendowicz, Ludwik K

    2009-04-01

    Precerebellins (Cbln) belong to the C1q/TNF superfamily of secreted proteins which have diverse functions. They are abundantly expressed in the cerebellum, however, three of them are also expressed in the rat adrenal gland. All members of the Cbln family form homomeric and heteromeric complexes with each other in vitro and it was suggested that such complexes play a crucial role in normal development of the cerebellum. The aim of our study was to investigate whether Cbln1-derived peptides, cerebellin (CER) and des-Ser1-cerebellin (desCER) are involved in regulating biological functions of rat adrenocortical cells. In the primary culture of rat adrenocortical cells, 24 h exposure to CER or desCER notably stimulated corticosterone output and inhibited proliferative activity and similar effects were evoked by ACTH. To study gene transcript regulation by CER, desCER and ACTH, we applied Oligo GEArray DNA Microarray: Rat Signal Transduction Pathway Finder. In relation to the control culture, 13 of the 113 transcripts present on the array were differentially expressed. These transcripts were either up- or down-regulated by ACTH and/or CER or desCER treatment. Validation of DNA Microarray data by QPCR revealed that only 5 of 13 genes studied were differentially expressed. Of those genes, Fos and Icam1 were up-regulated and Egr1 was down-regulated by ACTH, CER and desCER. The remaining two genes, Fasn (insulin signaling pathway) and Hspb1 (HSP27) (stress signaling pathway), were regulated only by CER and desCER, but not by ACTH. Thus, both CER and desCER have effects similar to and different from corticotrophin on the intracellular signaling pathway gene expression in cultured rat adrenocortical cells.

  20. Gradual loss of ACTH due to a novel mutation in LHX4: comprehensive mutation screening in Japanese patients with congenital hypopituitarism.

    Science.gov (United States)

    Takagi, Masaki; Ishii, Tomohiro; Inokuchi, Mikako; Amano, Naoko; Narumi, Satoshi; Asakura, Yumi; Muroya, Koji; Hasegawa, Yukihiro; Adachi, Masanori; Hasegawa, Tomonobu

    2012-01-01

    Mutations in transcription factors genes, which are well regulated spatially and temporally in the pituitary gland, result in congenital hypopituitarism (CH) in humans. The prevalence of CH attributable to transcription factor mutations appears to be rare and varies among populations.This study aimed to define the prevalence of CH in terms of nine CH-associated genes among Japanese patients. We enrolled 91 Japanese CH patients for DNA sequencing of POU1F1, PROP1, HESX1, LHX3, LHX4, SOX2, SOX3, OTX2, and GLI2. Additionally, gene copy numbers for POU1F1, PROP1, HESX1, LHX3, and LHX4 were examined by multiplex ligation-dependent probe amplification. The gene regulatory properties of mutant LHX4 proteins were characterized in vitro. We identified two novel heterozygous LHX4 mutations, namely c.249-1G>A, p.V75I, and one common POU1F1 mutation, p.R271W. The patient harboring the c.249-1G>A mutation exhibited isolated growth hormone deficiency at diagnosis and a gradual loss of ACTH, whereas the patient with the p.V75I mutation exhibited multiple pituitary hormone deficiency. In vitro experiments showed that both LHX4 mutations were associated with an impairment of the transactivation capacities of POU1F1 andαGSU, without any dominant-negative effects. The total mutation prevalence in Japanese CH patients was 3.3%. This study is the first to describe, a gradual loss of ACTH in a patient carrying an LHX4 mutation. Careful monitoring of hypothalamic-pituitary -adrenal function is recommended for CH patients with LHX4 mutations.

  1. Síndrome de Guillain-Barré: a propósito de três casos, sendo um tratado pelo ACTH

    Directory of Open Access Journals (Sweden)

    José Lamartine de Assis

    1953-06-01

    Full Text Available O autor tece considerações sôbre a posição atual da síndrome de Guillain-Barré em face dos progressos recentes da virulogia, da experimentação e da terapêutica. Ao mesmo tempo procura justificar a aproximação daquela síndrome do grupo das afecçÕes desmielinizantes do sistema nervoso, com base nas observações próprias e naquelas encontradas na literatura; estas são de ordem clínica, anátomo-clínica e terapêutica, enquanto as primeiras são de ordem clínica e terapêutica. Dos três casos apresentados, os dois primeiros eram crônicos e com seqüelas irreversíveis, enquanto o terceiro era agudo e foi tratado pelo ACTH na dose de 15 mg em sôro glicosado isotônico, em gôta a gôta, por via intravenosa, durante 8 horas, diàriamente. Nos dois primeiros casos foi conseguida a recuperação da marcha sem apôio, sendo que, no primeiro, conseguiu-se, também, a recuperação satisfatória da movimentação ativa dos membros superiores, permitindo ao enfêrmo desincumbir-se sòzinho das suas atividades habituais indispensáveis. No caso 1 havia edema de papila bilateral que regrediu muito lentamente, além de bloqueio parcial transitório do canal raquidiano com líquor xantocrômico ; no caso 2 era de notar uma síndrome cordonal posterior dominante; no caso 3 havia, como fato digno de realce, comprometimento do miocárdio. Neste caso a remissão da sintomatologia clínica e a melhora progressiva das alterações eletrocardiográficas coincidiram com o emprêgo do ACTH.

  2. 促肾上腺皮质激素依赖性库欣综合征的诊断与治疗策略%The strategy for diagnosis and management of ACTH-dependent Cushing's syndrome

    Institute of Scientific and Technical Information of China (English)

    陆召麟

    2010-01-01

    Majority of the patients (about 80% ) with Cushing's syndrome are ACTH-dependent,which including pituitary-dependent Cushing's syndrome and ectopic ACTH syndrome. The diagnosis and treatment of this disease is rather complicated and difficult. A lot of progresses in this field have been made within the recent decades, though there are still many problems. Here introduces and evaluates the methods which are used widely for diagnosis, differential diagnosis and treatment. The strategy of the choice making are discussed. Brief introduction for guideline on the diagnosis of Cushing's syndrome and for the consensus of ACTH-dependent Cushing's syndrome which was published in 2008 is also be made.%促肾上腺皮质激素(ACTH)依赖性库欣综合征占库欣综合征病例总数的80%,主要包括垂体性库欣综合征和异位ACTH综合征.ACTH依赖性库欣综合征的诊断和治疗比较复杂,也比较困难.近年来,本病的诊断和治疗有很大的进步,但还存在不少问题.现对目前广泛应用于ACTH依赖性库欣综合征的各种诊断、鉴别诊断及治疗方法进行介绍和评价,并讨论治疗方法的选择以及治疗效果的评估.还对国际内分泌学会于2008年发表的关于库欣综合征的诊断指南及欧洲神经内分泌学会和垂体学会关于ACTH依赖性库欣综合征治疗的共识作简要介绍.

  3. Activation of the dopamine receptor type-2 (DRD2) promoter by 9-cis retinoic acid in a cellular model of Cushing's disease mediates the inhibition of cell proliferation and ACTH secretion without a complete corticotroph-to-melanotroph transdifferentiation.

    Science.gov (United States)

    Occhi, Gianluca; Regazzo, Daniela; Albiger, Nora Maria; Ceccato, Filippo; Ferasin, Sergio; Scanarini, Massimo; Denaro, Luca; Cosma, Chiara; Plebani, Mario; Cassarino, Maria Francesca; Mantovani, Giovanna; Stalla, Günter K; Pecori Giraldi, Francesca; Paez-Pareda, Marcelo; Scaroni, Carla

    2014-09-01

    Cushing's disease (CD) is a rare condition in which hypercortisolemia is secondary to excessive ACTH release from a pituitary corticotroph adenoma. CD is associated with significant morbidity and mortality, and a safe therapy that effectively targets the pituitary tumor is still lacking. Retinoic acid (RA) and dopamine agonists (DAs) have recently been considered as monotherapy in CD patients, and satisfactory results have been reported, albeit in a limited number of patients. Given the permissive role of RA on the dopamine receptor type-2 (DRD2), the aim of the present study was to see whether a combination of 9-cis RA and the DA bromocriptine (Br) might represent a possible treatment for CD. Here we show that 9-cis RA induces a functional DRD2 in the pituitary corticotroph cell line AtT20, and increases cell sensitivity to Br via a mechanism only partially related to corticotroph-to-melanotroph transdifferentiation. In addition, 9-cis RA and Br act synergistically to modulate cell viability, with favorable implications for clinical use. In nearly 45% of corticotropinoma-derived primary cultures, the combined administration of 9-cis RA and Br lowered the steady-state level of the ACTH precursor proopiomelanocortin (POMC) more efficiently than either of the drugs alone. In conclusion, the effects of a combination of 9-cis RA and Br on ACTH synthesis/secretion and cell viability in AtT20, and on POMC transcriptional activity in human corticotropinomas might represent a suitable starting point for assessing the potential of this treatment regimen for ACTH-secreting pituitary adenomas. This study thus has potentially important implications for novel therapeutic approaches to CD.

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

    Science.gov (United States)

    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.

  5. Complicações neurológicas no decurso de tratamento pelo ACTH: A propósito de um caso de agnosia visual

    Directory of Open Access Journals (Sweden)

    O. Freitas Julião

    1953-12-01

    Full Text Available Os autores relatam a observação de um menino de 8 anos de idade, portador de síndrome nefrótica tratada pelo ACTH e que apresentou uma série de graves distúrbios neurológicos conseqüentes a uma crise hipertensiva (a pressão arterial elevou-se a 220-130 mm Hg, ocorrida por ocasião desse tratamento. Manifestando-se inicialmente por cefaléia intensa, depois por crise convulsiva generalizada, à qual se seguiu estado comatoso e posteriormente síndrome confusional, a encefalopatía hipertensiva condicionou, como seqüelas neurológicas mais importantes, distúrbios visuais. Êstes, que se apresentaram, a princípio, sob a forma de amaurose total, assumiram depois o aspecto de distúrbios da percepção, tipo agnóstico, persistentes ainda hoje. A agnosia visual refere-se aos objetos, pessoas, figuras simbólicas e côres.

  6. Increased anxiety induced by listening to unpleasant music during stress exposure is associated with reduced blood pressure and ACTH responses in healthy men.

    Science.gov (United States)

    Jezova, Daniela; Hlavacova, Natasa; Makatsori, Aikaterini; Duncko, Roman; Loder, Ingrid; Hinghofer-Szalkay, Helmut

    2013-01-01

    The relationship between anxiety and the neuroendocrine response to stress stimuli is still not fully understood. The aim of this study was to evaluate the contribution of an acute increase in state anxiety to neuroendocrine activation under stress conditions. To do so, it was necessary to find a stress condition of the same character and intensity with and without a rise in state anxiety. We decided to examine the effects of listening to music on anxiety and to apply a new methodological approach. A group of 14 healthy volunteers participated in a counterbalanced crossover design study. The stress procedure consisted of mental (Stroop test, mental arithmetic) and physical (handgrip exercise) tasks combined with listening to music played forward (pleasant) or backwards (unpleasant). The results confirmed our hypothesis, namely the condition with listening to unpleasant music was anxiogenic, while the other was not. In case of increased state anxiety, the rise in ACTH concentrations in response to mental challenge and the increase in systolic blood pressure induced by handgrip exercise was reduced compared to the situation with unchanged anxiety. Concentrations of testosterone, oxytocin, vasopressin and aldosterone were slightly increased in response to the stress paradigm accompanied with increased anxiety. In conclusion, the present data demonstrate that an acute increase in state anxiety contributes to neuroendocrine activation under stress conditions. Moreover, the results show that listening to music may both positively and negatively influence the perception of stress and the level of anxiety, which might have functional consequences.

  7. The measurement of glucocorticoid concentrations in the serum and faeces of captive African elephants (Loxodonta africana after ACTH stimulation : research communication

    Directory of Open Access Journals (Sweden)

    S.K. Stead

    2000-07-01

    Full Text Available Conventionally, the assessment of adrenal responses to stress relies on blood sample collection. However, blood collection from animals is impossible without restraint or immobilisation that influences results. This study was undertaken to validate recently established enzyme immunoassays that measure faecal glucocorticoid metabolites in elephants, and to perform a preliminary investigation into the biological relevance of this non-invasive method for use in assessing the degree of stress in this species. Four juvenile African elephants were injected i.m. with 2.15 mg synthetic adrenocorticotrophic hormone (Synacthén, Novartis, Switzerland. Blood and faecal samples were collected over 4 h and 7 d respectively. Concentrations of serum cortisol and faecal cortisol metabolites were determined using immunoassay. Variability of basal and peak values in blood and faeces was observed among the elephants. After ACTH injection, serum cortisol concentrations increased by 400-700 %. An 11-oxoaetiocholanolone enzyme immunoassay (EIA proved best suited to measure cortisol metabolites (11,17-dioxoandrostanes when compared to a cortisol and corticosterone EIA in faecal samples. Concentrations of faecal 11,17-dioxoandrostanes increased by 570-1070 %, reaching peak levels after 20.0-25.5 h. Greater levels of glucocorticoid metabolites were measured in faecal samples from elephants kept in small enclosures compared to levels in the faeces of animals ranging over a larger area. The results of this preliminary study suggest that non-invasive faecal monitoring of glucocorticoid metabolites is useful in investigating adrenal activity in African elephants.

  8. Hiperplasia adrenal congênita: dosagem da 17-hidroxiprogesterona basal para seleção e casos para realização do teste de estímulo com ACTH sintético Congenital adrenal hyperplasia: measurement of basal 17-hydroxyprogesterone as a screening test to select patients for the synthetic ACTH provocative test

    Directory of Open Access Journals (Sweden)

    Lúcia Helena Coelho Nóbrega

    2004-05-01

    Full Text Available OBJETIVOS: avaliar se os níveis de 17-hidroxiprogesterona podem predizer o resultado do teste de estímulo como diagnóstico de hiperplasia adrenal congênita, forma tardia. MÉTODOS: foram incluídas no estudo e avaliadas retrospectivamente 122 pacientes com suspeita clínica de hiperplasia adrenal congênita forma tardia. Essa suspeita clínica incluía sinais e/ou sintomas de hiperandrogenismo (hirsutismo, acne, pele oleosa, irregularidade menstrual, etc.. Todas as pacientes foram submetidas ao teste de estímulo da adrenal com ACTH sintético 0,25 mg (Synacthen®. Após repouso de 60 minutos as amostras foram colhidas nos tempos basal e 60 minutos após a administração de 0,25 mg de ACTH sintético para dosagem de 17-hidroxiprogesterona, sendo mantido o acesso venoso com catéter heparinizado. Foi utilizado o método de radioimunoensaio para realizar as dosagens séricas da 17-hidroxiprogesterona. A sensibilidade e a especificidade da 17-hidroxiprogesterona basal como teste de rastreamento para hiperplasia adrenal congênita foram medidas, avaliando vários pontos de corte. Curvas ROC foram feitas para analisar a performance do teste, utilizando o software Medcalc®. RESULTADOS: a análise por curva ROC mostrou um ponto de corte de 181 ng/dl acima do qual dever-se-ia realizar o teste de estímulo, bem próximo a 200 ng/dl, mais comumente aceito pela literatura. Níveis séricos da 17-hidroxiprogesterona mais altos que 200 ng/dl têm valores preditivo positivo e negativo de 75% e 100% e acurácia de 98,4% como diagnóstico de hiperplasia adrenal não-clássica. CONCLUSÕES: considerando os dados, sugerimos que pacientes com hiperandrogenismo clínico devam iniciar a investigação com 17-hidroxiprogesterona basal e, caso esta se mostre acima de 181 ng/dl, sigam a investigação com o teste de estímulo com ACTH sintético.INTRODUCTION: adrenal hyperplasia is a common genetic disorder and 95% of the cases are due to a 21-hydroxylase

  9. 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.

    Science.gov (United States)

    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.

  10. Distúrbios neurológicos e electrolíticos em nefrótico após diurese rápida provocada pelo ACTH

    Directory of Open Access Journals (Sweden)

    Hedda Arminante de Oliveira Penna

    1960-03-01

    Full Text Available Os autores apresentam o caso de criança de 10 anos, portadora de síndrome nefrótica, que, durante a fase de diurese rápida conseqüente à administração de ACTH, apresentou crises convulsivas, coma, alterações do electrencefalograma, do electrocardiograma, hiponatremia, hipocalemia, hipocloremia e alcalose. Como principais seqüelas, o paciente apresentava, ao ter alta hospitalar, síndrome convulsiva e hemianopsia homônima lateral direita. Os autores comentam o possível mecanismo dessas alterações.

  11. ACTH非依赖性Cushing综合征的分子生物学研究进展%Research advance in molecular biochemistry of ACTH-independent Cushing syndrome

    Institute of Scientific and Technical Information of China (English)

    蒋怡然; 王卫庆

    2010-01-01

    促肾上腺皮质激素(ACTH)非依赖性Cushing综合征包括肾上腺皮质腺瘤、肾上腺皮质癌和肾上腺皮质结节样增生,其发病机制主要与基因突变(GNAS1、PRKAR1A和PDE11A)、异位受体表达、WNT通路异常激活及抑癌基因杂合丢失等诸多因素相关,该文就上述发病机制作一综述.

  12. Tratamento dos casos graves de miastenia: ação do ACTH e cortisona. Considerações a propósito de três casos

    Directory of Open Access Journals (Sweden)

    José Lamartine de Assis

    1956-03-01

    Full Text Available São apresentados 3 casos de miastenia grave em que os recursos terapêuticos clássicos não deram resultado favorável. Os 3 pacientes foram, então, submetidos ao tratamento pelo ACTH e cortisona; em todos houve remissão da sintomatologia, remissão que perdurou até cêrca de um mês após a suspensão da hormonioterapia. O tratamento foi repetido várias vêzes de acôrdo com a evolução da doença. É de notar que em 2 pacientes (casos 1 e 2, foram estabelecidas doses mínimas de manutenção controladas durante cerca de 40 dias. O ACTH foi usado por via intravenosa em doses variáveis de 2,5 a 25 mg, diluído em 250 a 1000 ml de sôro glicosado isotônico, na velocidade de 20 a 25 gotas por minuto. Em todos os casos, durante a hormonioterapia, foi administrada prostigmina em doses muito pequenas.

  13. 非ACTH依赖性双侧肾上腺大结节增生患者的临床特点分析%A study on clinical features of ACTH-independent bilateral macronodular adrenal hyperplasia

    Institute of Scientific and Technical Information of China (English)

    张倩; 巴建明; 母义明; 陆菊明; 潘长玉; 窦京涛; 谷伟军; 杜锦; 王先令; 杨国庆; 郭清华; 杨丽娟; 吕朝晖

    2011-01-01

    Objective To study the clinical features of patients with ACTH-independent bilateral macronodular adrenal hyperplasia(AIMAH).Methods Eighteen cases with AIMAH diagnosed in Chinese PLA General Hospital from 1998 to 2010 were analyzed retrospectively.Results ( 1 ) AIMAH was equally distributed between genders,mean age at diagnosis was ( 51.4 ± 10.7 ) years,and average course was ( 9.9:t:2.7 ) years.( 2 )Most patients visited hospital because of adrenal incidentaloma; hypertension and impaired glucose tolerance/diabetes mellitius were the most common clinical presentations; typical signs of Cushing′s syndrome (CS) such as moon face and central obesity were less frequent.( 3 ) All cases′ laboratory findings met the diagnostic criteria of ACTH-independent CS,some cases with the features of subclinical CS.24 h dynamic plasma ACTH and cortisol monitoring had the advantage of revealing the features of subclinical CS for some AIMAH cases; there was remarkable elevation of plasma cortisol after exogenous ACTH stimulation in AIMAH patients.(4) Bilateral adrenal macronodular changes could be visualized on CT scan.( 5 ) Pathology identified bilateral macronodular adrenal hyperplasia.( 6 ) Bilateral adrenalectomy was the most useful treatment.Conclusions AIMAH is an infrequent cause of CS,and some patients present subclinical CS.Its marked clinical feature is ACTH-independent bilateral macronodular adrenal hyperplasia.%目的 探讨非ACTH依赖性双侧肾上腺大结节增生(AIMAH)患者的临床特点.方法 回顾性分析1998年至2010年解放军总医院内分泌科收治并确诊的18例非ACTH依赖性双侧肾上腺大结节增生患者的临床资料.结果 (1) AIMAH患者男女比例1∶1,平均就诊年龄(51.4±10.7)岁,平均病程(9.9±2.7)年;(2)部分患者因体检意外发现肾上腺占位就诊;高血压、糖代谢异常最常见,满月脸、向心性肥胖等典型的库欣综合征(CS)体征较少见;(3)实验室检查示患者均为非ACTH

  14. 危重症时早产儿促肾上腺皮质激素、皮质醇及醛固酮的变化%ACTH, cortisol and aldosterone level of preterm infants with critical illness

    Institute of Scientific and Technical Information of China (English)

    吴运芹; 薄涛; 李正秋; 高喜容; 黄瑞文; 颜卫群; 肖勇; 马金霞

    2010-01-01

    目的 以血清皮质醇、醛固酮、促肾上腺皮质激素(ACTH)水平作为监测指标,观察危重症对早产儿下丘脑-垂体-肾上腺(HPA)轴相关激素的影响.方法 以出生72 h内的早产儿90例(胎龄0.05).结论 早产儿应激发生时机体已具有调节皮质醇分泌的能力,胎龄越大,这种能力越成熟.危重症时早产儿血清皮质醇浓度增高,血清醛固酮、ACTH浓度与疾病的严重程度无显著相关性.%Objective To investigate the effect of illness severity on preterm infant's hypothalamusputituary-adrenal (HPA) axis, we measured the serum concentration of cortisol,aldosterone and adrenocorticotropic hormone (ACTH). Methods Ninety preterm infants who were transferred to our hospital within 72 hours after birth were involved. These preterm infants were divided into two groups:gestational age (GA) ≥34 weeks' preterm infants and GA <34 weeks' preterm infants. We evaluated these preterm infants at the time of admission,day 7 and day 14 after birth with neonatal critical illness score (NCIS). Then they were divided into mild group and severe group by the lowest score. We measured their serum cortisol,aldosterone and ACTH at the time of admission,day 7 and day l4 after birth. Results (1) The serum cortisol concentration of preterm infants with severe illness was higher than that of preterm infants with mild illness. Among the GA ≥34 weeks' preterm infants,the serum cortisol concentration of preterm infants with severe illness was significandy higher than that of preterm infants with mild illness within 72 hours after birth (t = -2.263,P =0. 029). Among the GA <34 weeks' preterm infants,the serum cortisol concentration of preterm infants with severe illness was significantly higher than that of preterm infants with mild illness on day 14 after birth (t =-2. 913 ,P =0. 006). (2) Among the preterm infants with severe illness,the serum cortisol concentration of the GA≥34 weeks' was significantly higher than that

  15. Study on plasma level of ACTH and cortisol in polycystic ovary syndrome patients with and without hyperandrogenemia%多囊卵巢综合征伴或不伴高雄激素血症患者血浆促肾上腺皮质激素和皮质醇水平研究

    Institute of Scientific and Technical Information of China (English)

    谢艳妮; 王娈; 马瑞欣

    2013-01-01

    Objective To compare plasma level of adrenocorticotropic hormone (ACTH) and cortisol between polycystic ovary syndrome (PCOS) patients with and without hyperandrogenemia.Methods 109 PCOS patients and 36 healthy controls were enrolled in this study.Height,weight,waist circumference,hip circumference were measured and body mass index,waist/hip ratio were calculated.Hirsutism and acne scoring were graded.Fasting blood samples were collected at 8am for measurement of luteinizing hormone (LH),follicular stimulating hormone (FSH),total testosterone,prolactin,estrogen,sex hormone binding globulin (SHBG),dehydroepiandrosterone sulfate (DHEAS),adrenocorticotropic hormone(ACTH)and cortisol.Blood sample was also collected at 4pm on the same day to measure plasma ACTH and cortisol level.LH/FSH ratio,free androgen index(FAI),4pm/8am ratio of ACTH,4pm/8am ratio of cortisol,ACTH and cortisol circadian rhythm disappear rate were calculated.In order to evaluate homeostasis model of insulin resistance (HOMA-IR) and pancreatic β cell function (HOMA-β),fasting blood glucose and serum insulin were measured.All subjects were examined by ultrasound.All the PCOS patients were divided into two groups,hyperandrogenemia group (FAI ≥ 4.5) and non-hyperandrogenemia group (FAI < 4.5).The clinical features,biochemical parameters,plasma levels of ACTH & cortisol and their circadian rhythm were compared between PCOS patients and healthy controls,as well as PCOS patients with and without hyperandrogenemia.To exclude the influence of obesity on ACTH,cortisol results,PCOS patients and healthy controls with normal BMI were further compared.Results (1) Compared with healthy controls,the PCOS patients had significantly higher LH,LH/FSH ratio,total testosterone,DHEAS,FAI,ACTH-8am,ACTH circadian rhythm disappear rate (P < 0.05) and significantly lower SHBG(P < 0.05).The statistical differences of other indexes were not seen between two groups(P >0.05).(2)Total testosterone,FAI,ACTH-8am,ACTH-4

  16. SLE患者血浆β-内啡肽和ACTH水平变化及临床意义%Detection and the significance of beta- endorphin and ACTH in systemic lupus erythematosus

    Institute of Scientific and Technical Information of China (English)

    李久宏; 刘继峰; 李波; 翟宁; 耿龙; 宋芳吉

    2003-01-01

    目的:探讨β-内啡肽(β-endorphin,β-EP)、促肾上腺皮质激素(ACTH)是否与SLE的发病有关.方法:采用放射免疫分析法测定30例SLE患者血浆β-内啡肽、ACTH水平,并与20例正常对照组相比较.结果:SLE患者血浆β-内啡肽水平与正常对照组相比显著降低,P<0.01;ACTH水平与正常对照组相比差异无显著性,P>0.05.结论:结果表明β-内啡肽与SLE发病可能存在一定关系.

  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.

    Science.gov (United States)

    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. Protocolo de investigación de evaluación de niveles de interleucinas en niños con encefalopatía epiléptica candidatos al uso de hormona adrenocorticotropa (ACTH), diagnosticados en la Liga Central Contra la Epilepsia entre los años 2013 y 2014

    OpenAIRE

    Benítez Ramírez, Diana Carol

    2015-01-01

    Objetivo: Realizar un protocolo de investigación que permita determinar la modificación de los valores de interleucinas en niños con encefalopatía epiléptica que reciben tratamiento con ACTH. Métodos: Se realizó una amplia búsqueda de bibliografía en diferentes bases de datos usando términos MESH sobre los temas inflamación, epilepsia y ACTH, se definió la hipótesis de trabajo y los objetivos, posteriormente se definió la población objetivo del estudio, se eligió el esquema de aplicación de A...

  19. 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.

    Science.gov (United States)

    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 sulpiride and TRH injection and were greater (P sulpiride and TRH injection, and the response was greater (P sulpiride; no effect of insulin sensitivity was observed. Plasma thyroid-stimulating hormone (TSH) concentrations responded (P 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 consistent with our previous observation of elevated plasma triiodothyronine concentrations in hyperleptinemic horses (later shown to be insulin insensitive as well).

  20. The value of bilateral inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome%双侧岩下窦静脉采血诊断ACTH依赖性库欣综合征的价值

    Institute of Scientific and Technical Information of China (English)

    周薇薇; 宁光; 王卫庆; 张华; 苏颋为; 蔡剑飞; 蒋怡然; 方文强; 孙青芳; 卞留贯

    2012-01-01

    Objective To evaluate the values of bilateral inferior petrosal sinus sampling ( BIPSS),high dosage dexamethasone suppression test (HDDST) and pituitary image in the differential diagnosis of ACTH-dependent Cushing's syndrome. Methods Totally 87 patients with confirmed pathological diagnosis were recruited in the study.All received the procedure of BLPSS,HDDST,and pituitary MRI with dynamic enhancement.The diagnostic performances of three differential diagnosis methods in ACTH-dependent Cushing's syndrome were evaluated.Results Seventy-eight patients were diagnosed as cases of pituitary ACTH adenoma,and the remaining 9 were confirmed cases of ectopic ACTH syndrome due to the thymic carcinoid.The sensitivity and specificity of HDDST,pituitary MRI,and BIPSS for the diagnosis of ACTH-dependent Cushing's syndrome were 82.1% and 100%,79.5% and 44.4%,92.3% and 100%,respectively.In Cushing's disease,the diagnostic accuracy was 83.9% with HDDST,77.0%with pituitary MRI,and93.1% with BIPSS.In those patients with Cushing's disease,the coincidence of lateralization was 83.9% with BIPSS and 64.5% with MRII.Conclusion BIPSS was better than the other two methods in differential diagnosis of ACTH-dependent Cushing's syndrome.Compared with the pituitary MRI,the concordant rate of BIPSS in lateralization of the tumor is higher,and it is more reliable.%目的 评估双侧岩下窦静脉采血(BIPSS)测定ACTH、垂体MRI动态增强和大剂量地塞米松抑制试验在ACTH依赖性库欣综合征鉴别诊断中的价值.方法 纳入BIPSS并经病理明确诊断的ACTH 依赖性库欣综合征患者87例,行BIPSS、大剂量地塞米松抑制试验和垂体影像学评估.结果 78例病理明确诊断为垂体ACTH瘤,9例为胸腺类癌所致异位ACTH综合征.大剂量地塞米松抑制试验、垂体MRI动态增强和BIPSS诊断敏感性分别为82.1%、79.5%和92.3%,特异性分别为100%、44.4%和100%,诊断准确率分别为83.9%、77.0

  1. Histamine H3 receptors regulate ACTH release by AtT-20 cel ls%组胺H3受体对垂体瘤AtT-20细胞分泌ACTH的调节作用

    Institute of Scientific and Technical Information of China (English)

    谢建军; 罗晓星; 赵德化

    2001-01-01

    AIM To investigate the signal transduction mechanism of histamine H3 r eceptor. METHODS The adrenocorticotropic hormone (ACTH) levels of supernatants on AtT- 20 cells from the pituitary gland tumor were measured by radioimmunoassa y at the given time after histamine agonists were administrated and the effects o f R-(α)-methylhistamine on the cells proliferation were observed. RES ULTS The H3 receptor specific agonist, R-(α)-methylhistamine incre ased the release of A CT H in time-dependent manner. It increased significantly after administrated r e agents 8 h which reached 1920 μg*L-1 compared to the control group 7 80 μg*L-1 . while the H1 receptor agonist 2-methylhistamine and the H2 agonist impro midine were significantly less potent. Furthermore, this response was blocked by thiop eramide, an H3 receptor specific antagonist, but not by the H1 and H2 anta gonist chlorpheniramine and cimetidine. R-(α)- methylhistamine had no significant i nf luence on cell proliferation within 24 h. Pretreatment with N-ethylmaleimide (N EM ) could abolish the effects of R-(α)-methylhistamine on the release of ACTH. CO NCLUSION Specific activation of H3 receptor could evoke the excitatio n-secreti on coupling process, and G protein might be involved in the signal transdu ction.%目的 观察组胺受体激动剂对AtT-20细胞分泌ACTH的影响,并探讨G蛋 白在组胺H3 受体信号转导机制中的作用. 方法 选用文献报道的高表达组胺H3受体 的垂体细胞瘤AtT-20 作为观察系统,用放免分析法测定给予组胺受体激动剂后各时间点细胞上清液中ACTH分泌量 的变化,并观察药物对细胞增殖的影响. 结果 组胺H3受体激动剂R- (α)- MeHA(0.1 μmol*L-1)作用8 h能明显促进ACTH的释放,释放量为1920 μg * L-1,与同时间对照组(780 μg*L-1)相比,明显增高(P<0.01);H 1和H2激动剂则无此作用. 且R-(α)-MeHA引起ACTH分泌 的效应能被H3受体特异

  2. Clinical Significance of Changes on Serum Cortisol and ACTH in Impaired Glucose Regulation and Type 2 Diabetics%血清Cortisol及ACTH在糖调节受损和DM2患者中的变化及意义

    Institute of Scientific and Technical Information of China (English)

    周晓莉; 饶一武

    2013-01-01

    目的:探讨血清皮质醇(Cortisol)及促肾上腺皮质激素(ACTH)在糖调节受损(IGR)和2型糖尿病(DM2)患者中的变化及意义.方法:比较糖调节受损组、DM2组与正常对照组在8:00及24:00两次的血清Cortisol和ACTH水平;并进一步将糖调节受损组分为糖耐量减低(IGT)组和空腹血糖受损(IFG)组分别与DM2组比较8:00及24:00两次的血清Cortisol和ACTH水平.结果:①IGR和DM2组患者8:00及24:00两次的Cortisol和ACTH较正常对照组升高,差异有统计学意义(P<0.01或P< 0.05);②DM2组8:00血清Cortisol和ACTH水平低于IGT组和IFG组,差异有统计学意义(P<0.01或P< 0.05);③IGR和DM2患者血清Cortisol及ACTH水平相关分析显示Cortisol、ACTH间呈正相关(r=0.4002、0.4231,P<0.05).结论:IGR和DM2患者体内存在以血清Cortisol及ACTH分泌增高为主要表现的HPA轴功能紊乱,且随病情进展HPA轴有功能"耗竭"的趋势.

  3. 著しい筋力低下を認めたACTH 非依存性両側副腎皮質大結節性過形成(AIMAH)の一例

    OpenAIRE

    山田 , 穂高; 佐々木, 正美; 浅野 , 智子; 青木  , 厚; 生駒 , 亜希; 豊島 , 秀男; 加計 , 正文; 川上 , 正舒; 石川 , 三衛

    2013-01-01

    68歳男性。入院4年前から両側下肢筋力低下が出現,3年前から近医で糖尿病,高血圧を指摘され加療を受けていた。高血圧のスクリーニングで撮像した腹部CT で両側副腎の多結節状腫大を指摘され,当科を紹介受診した。血清コルチゾール34.9μg/dL,デキサメサゾンでの抑制なく,クッシング症候群が考えられ,精査目的に入院となった。入院時の身体所見では明らかなクッシング兆候は見られなかった。精査の結果ACTH 非依存性両側副腎皮質大結節性過形成(AIMAH)によるクッシング症候群と診断した。バソプレシンによるコルチゾールの分泌亢進が認められ,AIMAH 組織内のバソプレシン受容体発現が強く推察された。...

  4. 成人特发性孤立性ACTH缺乏症三例临床分析并文献复习%Analysis of three patients with adult idiopathic isolated ACTH deficiency and literature review

    Institute of Scientific and Technical Information of China (English)

    郭清华; 陈康; 陆菊明; 母义明; 窦京涛; 吕朝晖; 巴建明; 李江源; 潘长玉

    2014-01-01

    Objective Adult idiopathic isolated ACTH deficiencv(AIIAD) is an underestimated disorder which is frequently misdiagnosed.In this paper,we presented 3 new cases of AIIAD and summarized the clinical characteristics by analyzing these cases and available literature for further understanding this disease.Methods Three cases of AIIAD in our hospital from 1998 to 2003 were retrospectively identified.Data of clinical features,laboratory findings,and response to treatment were collected.The clinical characteristics and pertinent literature were reviewed and analysed.Results These 3 cases of AIIAD aged 52-68 years old were misdiagnosed and incorrectly treated for 7 months to 4 years.All three cases presented the symptoms of fatigue and loss of weight at the onset,and were misdiagnosed as climacteric syndrome,thyroiditis,and gastrointestinal disease.The prevalence of AIIAD was very low,and it was thought to be an underestimated disorder.Through analyzing the 3 cases and literature review,the clinical features of this disease were summarized as follows:(1) Most patients were aged over 40 years and had no history of glucocorticoid medication.(2) Clinical presentations were insidious,with symptoms such as fatigue and weight loss.(3) Patients usually had no excessive pigmentation.(4) Hypogonadism in men and amenorrhea in women could be present.(5) Blood chemistry usually revealed hyponatremia but rarely hyperkalemia.(6) Blood lymphocytosis and eosinophilia were common.(7) Plasma ACTH and cortisol levels markedly decreased with normal secretion of other pituitary hormones.(8) High prevalence of thvroid disorder or positive anti-thyroid autoantibodv.(9) Usually the other accompanied autoimmune diseases might be ameliorated with glucocorticoid replacement.(10) MRI revealed no structural pituitary defects except for empty sella.(11) No evidence of infiltration,trauma,surgery,infection,and radiotherapy of the pituitary gland was found.Conclusions AIIAD is an unspecified and

  5. Comparison of two commercial kits and two extraction methods for fecal glucocorticoid analysis in ocelots (Leopardus pardalis submitted to ACTH challenge Comparação do desempenho de dois conjuntos comerciais e de dois métodos de extração para a análise de glicocorticóides fecais em jaguatiricas (Leopardus pardalis submetidas ao desafio com ACTH

    Directory of Open Access Journals (Sweden)

    Eduardo Antunes Dias

    2008-07-01

    Full Text Available The ocelot (Leopardus pardalis is included in list of wild felid species protected by CITES and is part of conservation strategies that necessarily involve the use of assisted reproduction techniques, which requires practical and minimally invasive techniques of high reproducibility that permit the study of animal reproductive physiology. The objective of this study was to compare and validate two commercial assays: ImmuChem Double Antibody Corticosterone 125I RIA from ICN Biomedicals, Costa Mesa, CA, USA; and Coat-a-Count Cortisol 125I RIA from DPC, Los Angeles, CA, USA, for assessment of fecal glucocorticoid metabolites in ocelots submitted to ACTH (adrenocorticotropic hormone challenge. Fecal samples were collected from five ocelots kept at the Brazilian Center of Neotropical Felines, Associação Mata Ciliar, São Paulo, Brazil, and one of the animals was chosen as a negative control. The experiment was conducted over a period of 9 days. On day 0, a total dose of 100 IU ACTH was administered intramuscularly. Immediately after collection the samples were stored at 20C in labeled plastic bags. The hormone metabolites were subsequently extracted and assayed using the two commercial kits. Previously it was performed a trial with the DPC kit to check the best extraction method for hormones metabolites. Data were analyzed with the SAS program for Windows V8 and reported as means ± SEM. The Schwarzenberger extraction method was slightly better when compared with the Wasser extraction method (103,334.56 ± 19,010.37ng/g of wet feces and 59,223.61 ± 12,725.36ng/g of wet feces respectively; P=0,0657. The ICN kit detected an increase in glucocorticoid metabolite concentrations in a more reliable manner. Metabolite concentrations (ng/g wet feces on day 0 and day 1 were 66,956.28 ± 36,786.93 and 92,991.19 ± 28,555.63 for the DPC kit, and 205,483.32 ± 83,811.32 and 814,578.75 ± 292,150.47 for the ICN kit, respectively. The limit of detection for the

  6. 吸毒人群血清ACTH、5-HT、β-内啡肽和cAMP水平的研究%A CLINICAL RESEARCH ON LEVELS OF ACTH,5-BT,β-ENDORPHIN,cAMP AND OTHER PARAMETERS OF DRUG ADDICTS

    Institute of Scientific and Technical Information of China (English)

    杨朝阳; 李灿东; 黄世庚; 吕京和

    2012-01-01

    Objective: To compare the levels of serum ACTH, 5 - HT, β - endorphin, cAMP among drug addicts and control subjects. Methods: The cases - control comparison between drug addicts and healthy people was adopted. Diagnosis standards of drug addicts conform to the standards in Chinese Classification of Mental Disorders, CCMD - 3. Results: There is a significant difference in cAMP level between drug addict group and healthy group, while no differences in 5 - HT, ACTH, β- endorphin between two groups were observed. Conclusion: The increased serum cAMP may be one of the factors that influence the emotion changes in drug addicts.%目的:研究吸毒人群血清ACTH、5-羟色胺(5-HT)、β-内啡肽和cAMP水平与健康人群的差异.方法:对吸毒者和健康者进行病例一对照研究,吸毒者诊断标准均符合第三版(CCMD-3).结果:吸毒组与健康组血清cAMP水平存在显著性差异;5-HT、ACTH、B-内啡肽水平在两组间无显著性差异.结论:吸毒人群血清cAMP的含量升高可能是影响情志改变的因素之一.

  7. 不同针刺方法对慢性应激抑郁大鼠下丘脑CRH基因表达及血清ACTH、CORT的影响%Influences of different acupuncture methods on hypothalamic CRH mRNA expression and serum ACTH and CORT in rats with chronic stress depression

    Institute of Scientific and Technical Information of China (English)

    梁佳; 卢峻; 王俊仁; 崔善福; 阿英格; 图娅

    2012-01-01

    Objective To compare and observe the differences between the influences of acupuncture and electroacupuncture on the expression of hypothalamic corticotrophin-releasing hormone ( CRH) mRNA and content of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in rat model of chronic stress depression, and investigate the mechanism of acupuncture and electroacupuncture in intervene and treatment of depression. Methods All SD rats were randomly divided into Wank group, model group, acupuncture group and electroacupuncture group. The expression of hypothalamic CRH mRNA was detected by using real-time fluorescence quantitative polymerase chain reaction (RT-PCR), and content of serum ACTH and CORT were detected by applying enzyme-linked immunosorbent assay (ELJSA). Results Compared with blank group, the expression of CRH mRNA and content of serum ACTH and CORT increased significantly in model group (P 0.05) , and ACTH expression decreased significantly (P 0. 05). Conclusion The rat model of chronic stress depression had a hyperactivity of HPA axis. Acupuncture and electroacupuncture can down-regulate the function of HPA axis. It may be one of ways to treat depression with acupuncture and electroacupuncture that they have antagonism to the hyperactivity of HPA axis.%目的 对比观察手针与电针对慢性应激抑郁模型大鼠下丘脑促肾上腺皮质激素释放激素(CRH)mRNA表达及血清促肾上腺皮质激素(ACTH)、皮质酮(CORT)影响的差异,探讨手针与电针干预治疗抑郁症的机制.方法 将SD大鼠随机分为4组:空白组、模型组、手针组、电针组,采用实时荧光定量PCR (RT-PCR)方法检测下丘脑CRH mRNA含量,酶联免疫吸附法(ELISA)检测大鼠血清ACTH、CORT含量.结果 与空白组相比,模型组大鼠下丘脑CRH mRNA的含量显著升高(P<0.01),血清CORT和ACTH含量显著升高(P<0.01).与模型组相比,手针组与电针组大鼠下丘脑CRH mRNA的含量均明显降低(P<0.05

  8. Change of serum ACTH and cortisol levels in Alzheimer disease and mild cognition impairment%阿尔茨海默病及轻度认知障碍患者血清促肾上腺皮质激素和皮质醇的变化

    Institute of Scientific and Technical Information of China (English)

    雷健康

    2010-01-01

    目的 探讨阿尔茨海默病(AD)、轻度认知障碍(MCI)患者早晨(8:00am)血清促肾上腺皮质激素(ACTH)、皮质醇水平变化及与疾病的关系.方法 纳入2007年7月5日至2009年3月31日在广州市天河区红十字会医院门诊或内科住院AD、MCI患者及健康志愿者,用化学发光免疫法检测54例AD患者、41例MCI患者及42名健康对照者早晨(8:00am)血清ACTH、皮质醇水平.结果 早晨血清ACTH水平AD组、MCI组及健康对照组分别为(16±5)、(16±5)、(17±4)ng/L,3组早晨血清ACTH比较差异无统计学意义(P>0.05);早晨血清皮质醇水平AD组、MCI组及健康对照组分别为(595±58)、(568±70)、(410±81)nmol/L,AD组、MCI组早晨血清皮质醇水平显著高于对照组(P<0.01),MCI组早晨血清皮质醇水平比AD组低,但差异无统计学意义(P>0.05);等级相关分析,血清皮质醇水平与AD的严重程度呈正相关(P<0.05);AD组血清皮质醇水平与MMSE评分存在负相关(P<0.05);性别之间比较血清皮质醇水平AD组、MCI组和健康对照组差异均无统计学意义(均P>0.05).结论 AD、MCI患者早晨血清ACTH水平无显著改变,皮质醇水平增高,且与AD严重程度呈正相关,与AD患者的MMSE评分存在负相关,性别与血清皮质醇水平无关.%Objective To characterize the response of adrenocortieotropic hormone(ACTH)and cortisol in the patients with Alzheimer disease(AD)and those with mild cognition impairment(MCI).Methods The AD or MCI patients at our department from July 5, 2007 to August 31,2009 were enrolled.The levels of 8am serum ACTH and cortisol were measured by chemiluminescence in 54 AD patients, 41 MCI patients and 42 age -matched controls. Results The serum ACTH values in 3 groups were(16 ±5),(16 ±5)and(17 ±4)ng/L respectively. The serum ACTH values had insignificant changes in 3 groups(P>0.05). The serum cortisol values were(595 ± 58),(568 ± 70)and(410 ± 81)nmol/L in 3 groups respectively. And the

  9. Adrenal function evaluation using ACTH stimulation test in children with sepsis and septic shock%促肾上腺皮质激素刺激对脓毒症及脓毒性休克患儿肾上腺功能评估的意义

    Institute of Scientific and Technical Information of China (English)

    张育才; 章赛吉; 滕国良; 田国力; 徐梁; 曹瑞芬; 张宇鸣

    2008-01-01

    目的 探讨小剂量(1μg/1.73 m2)促肾上腺皮质激素(ACTH)刺激实验评估儿童脓毒症和脓毒性休克肾上腺功能状态的价值.方法 患儿入院24h内完成基础皮质醇(T0)测定,静脉注射1μg/1.73m2 ACTH,30 min后测定血液皮质醇(T1),根据T0和皮质醇增值(△max=T1-T0)判断肾上腺功能,以△max≤90μg/L为肾上腺功能障碍(AI)指标.结果 62例中,脓毒症53例,脓毒性休克9例,病死率为27.4%(17/62).肾上腺功能障碍(adrenal insufficiency,AI)发生率40.3%(25/62),其中脓毒症和脓毒性休克患儿AI发生率分别是39.6%和44.4%,差异无显著统计学意义(P>0.05).两组脓毒症和脓毒性休克平均T0和T1分别是(318.6±230.4)μg/L、(452.3±230.7)μg/L和(454.7±212.7)μg/L、(579.3±231.9)μg/L,差异无统计学意义(P>0.05).存活组和死亡组患儿T0、T1分别是(320.5±223.9)μg/L、(462.3±212.0)μg/L和(384.3±258.3)μg/L、(500.7±470.6)μg/L,两组AI发生率分别是37.8%和47.1%,差异无统计学意义(P>0.05).T0和T1水平与儿童危重病例评分(PCIS)有关(P0.05).结论 儿童脓毒症和脓毒性休克患儿AI发生率较高.小剂量ACTH刺激实验可以判断严重感染患者肾上腺功能,可为激素治疗提供依据.%Objective Sepsis and septic shock remain a common problem that results in significant mortality and morbidity in pediatric intensive care units(PICU).According to literature,the use of more physiologic steroid replacement therapy is associated with hemodynamic and survival benefits in adult patients with relative adrenal insufficiency (RAI) and catecholamine-resistant septic shock.But little information is available in children.The aim of the current prospective study was to determine the prevalence of adrenal insufficiency in children with sepsis and septic shock using a low-dose adrenocorticotropic hormone(ACTH)stimulation test (1μg/1.73 m2) in children.Methods The authors performed cortisol estimation at baseline and after low-dose (1μg/1

  10. The efficacy and safety of different doses of ACTH therapy for infantile spasms: a meta-analysis%不同剂量促肾上腺皮质激素对婴儿痉挛症疗效和安全性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    崔晨; 王爽; 常杏芝; 秦炯

    2011-01-01

    目的 评价不同剂量促肾上腺皮质激素(ACTH)治疗婴儿痉挛症(IS)的疗效及安全性.方法 检索PubMed、EMBASE、Ovid、ScienceDirect、中国期刊全文数据库、万方数据库、CiNii(国立情報学研究所論文情報ナビゲータ)和Medical Online等数据库,并手工检索会议论文汇编和专题论文集等,收集关于不同剂量ACTH治疗IS的RCT文献.依据随机分配方法、分配隐藏、盲法、结果数据的完整性、选择性报告研究结果及其他偏倚来源进行文献偏倚评价.采用Review Manager 5.0软件进行Meta分析,无法进行合并分析的资料进行描述性分析.结果 共检索到836篇相关文献,符合纳入标准的4篇RCT文献进入Meta分析.文献偏倚评价结果显示,1篇文献存在中度偏倚风险,3篇文献存在高度偏倚风险.Meta分析结果显示,不同剂量ACTH组痉挛发作缓解率(OR=1.09,95%CI:0.54~2.17,P=0.82)、EEG高度失律消失率(OR=1.04,95%CI:0.43~2.51,P=0.94)及复发率(OR=1.27,95%CI:0.64~2.54,P=0.50)差异均无统计学意义.进一步按症状性和隐原性IS行亚组分析,结果显示两亚组不同剂量ACTH上述疗效指标差异均无统计学意义.大剂量ACTH组高血压和体重增加等不良反应的发生率高于小剂量ACTH组.结论 现有证据提示,不同剂量ACTH治疗IS在痉挛发作缓解率、EEG高度失律消失率及复发率方面疗效相近.小剂量 ACTH所致不良反应更少.鉴于纳入Meta分析的RCT文献数量较少且质量较低,明确结论仍需进一步的RCT研究.%Objective To assess the efficacy and adverse effects of different doses of ACTH on infantile spasms( IS ).Methods Systematic review and meta-analysis of RCTs were performed to compare the effects of different doses of ACTH on IS.The standard literature search strategy included electronic literature search and manual literature search.Electronic search was carried out in databases including PubMe.d, EMBASE

  11. 亚硒酸钠对实验性胃癌大鼠垂体 ACTH、GH和 TSH细胞的影响%Effect of sodium selenite on ACTH, GH and TSH positive cells of experimental gastric cancer rat pituitary

    Institute of Scientific and Technical Information of China (English)

    陈瑶瑶; 唐军民; 唐岩; 柯嘉; 毛卓; 孙红亚; 甄昱; 苏衍萍

    2014-01-01

    目的:观察亚硒酸钠在大鼠实验性胃癌发生过程中对垂体远侧部ACTH细胞、GH细胞和TSH细胞的免疫组织化学影响。方法:用断乳雄性Wistar大鼠62只,分正常对照组、N-甲基-N'-硝基-N-亚硝基胍( N-methyl-N'-nitro-N-nitrosoguanidine,MNNG)实验对照组、MNNG低硒组和MNNG高硒组。43周时取大鼠垂体和胃组织。用免疫组织化学ABC法显示垂体ACTH细胞、GH细胞和TSH细胞,结果进行图像分析。结果:MNNG实验对照组和加硒组均有数只大鼠胃浆膜面出现肿块,且光镜下显示为肠上皮化生,其中加硒组的肠化生率明显高于实验对照组(P<0.05)。图像分析结果显示,MNNG实验组、低硒组、高硒组大鼠垂体远侧部ACTH阳性细胞的平均光密度(MOD)分别为0.0623±0.02024、0.0680±0.08948和0.0574±0.01949;GH阳性细胞MOD分别为0.0380±0.01311、0.0415±0.01559和0.0293±0.01323;TSH阳性细胞数MOD分别为0.0943±0.18606、0.1272±0.05389和0.1044±0.04166。结论:在实验性大鼠胃癌形成过程中,低剂量亚硒酸钠组的大鼠腺垂体远侧部ACTH、GH和TSH阳性细胞反应增强;而高剂量亚硒酸钠的作用则完全相反。%Objective:To observe effect of sodium selenite on ACTH, GH and TSH cells in pars distalis of pituitary during the carcinogenesis of gastric cancer in rat. Methods:62 weaning male Wistar rats were divided into 4 groups: normal control group; N-methyl-N'-nitro-N-nitrosoguanidine( MNNG) experimental control group;MNNG low-selenium group;MNNG high-selenium group. At the 43rd weeks, the four groups of rat pituitary and gastric tissue were collected. Changes of ACTH, GH and TSH positive cells were detected using immunohistochemical ABC methods. The results were processed by image analysis. Results:Tumor mass appeared in gastric serosa and were shown intestinal metaplasia in gastric mucosa by light microscope in MNNG experiment control group and se-lenium group. And the intestinal

  12. Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome%精氨酸血管加压素刺激试验与大剂量地塞米松抑制试验在库欣病与异位促肾上腺皮质激素综合征诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    张微微; 余叶蓉; 谭惠文; 王椿; 李建薇; 安振梅; 刘玉平

    2016-01-01

    目的 探讨精氨酸血管加压素(DDAVP)刺激试验与大剂量地塞米松抑制试验(HDDST)在促肾上腺皮质激素(ACTH)依赖性库欣综合征诊断中的临床价值.方法 回顾性收集2010年1月1日至2015年9月30日于华西医院确诊的85例库欣病和10例异位ACTH综合征患者的临床资料,分析DDAVP刺激试验与HDDST诊断库欣病的敏感性、特异性以及联合两试验结果对库欣病诊断的符合率.结果 DDAVP刺激试验的敏感性与特异性为87%(39/45)和5/5,HDDST的敏感性与特异性为79% (67/85)和8/10,标准HDDST的敏感性高于过夜HDDST.上述两试验结果一致时对库欣病诊断的符合率为100%.结论 DDAVP刺激试验与HDDST对库欣病及异位ACTH综合征均有良好的诊断价值,两试验结合可进一步提高诊断的准确性.%Objective Toinvestigate the value of desmopressin (DDAVP)stimulation test and high dose dexamethasone suppression test (HDDST) inestablishing the cause of ACTH dependent Cushing's syndrome.Methods The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1,2010 to September 30,2015 was analyzed.The sensitivity and specificity of DDAVP stimulation test,HDDST,and the diagnostic accordance rate when the two tests were combined,were evaluated based on the diagnostic gold standard.Results A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included.The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5,respectively,whereas those of HDDST were 79% and 8/10,respectively.The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test.When the two tests had consistentresults,the diagnostic accordance rate was 100%.Conclusions DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease andectopic ACTH syndrome.The accuracy of diagnosis

  13. 促肾上腺皮质激素对改进的炎性痛大鼠脑、脊髓内CGRP的影响%Effects of ACTH on CGRP level in the brain and spinal cord in the rats with adjuvant-induced chronic arthritic pains

    Institute of Scientific and Technical Information of China (English)

    徐海伟; 李希成; 阮怀珍; 黎海蒂

    2000-01-01

    目的观察腹腔注射促肾上腺皮质激素(ACTH)对改进的完全佐剂性关节炎慢痛大鼠脊髓腰膨大,海马和纹状体内降钙素基因相关肽(Calcitonin gene-related peptide,CGRP)的影响.方法①肾上腺摘除术.②CGRP放射免疫法.结果①大鼠踝关节周围皮下注射自制的油包水型完全福氏佐剂成功地制备成一种全身反应较轻的慢性疼痛模型.②脊髓腰膨大中的CGRP在关节炎大鼠中升高,腹腔注射ACTH可以抑制关节炎大鼠脊髓腰膨大中CGRP的升高,摘除双侧肾上腺后ACTH的这种抑制作用消失.结论 ACTH通过肾上腺抑制佐剂性关节炎痛敏引起脊髓内CGRP增多而产生镇痛作用.

  14. Effects of Balance-acupuncture Stimulation of“Back Pain” and “Hip Pain”Points on Plasma β-endorphin and ACTH Contents in Rats with Lumbar Disc Herniation%平衡针对腰椎神经根压迫模型大鼠血浆β-内啡肽、促肾上腺皮质激素的影响

    Institute of Scientific and Technical Information of China (English)

    马文珠; 张艺萌; 袁红; 王文远

    2011-01-01

    Objective To observe the effect of balance acupuncture on the thermal pain threshold and plasma β-endor-phin (p-EP) and adrenocorticotrophic hormone (ACTH) levels in lumbar disc herniation rats so as to research its mechanisms underlying improvement of lumbar disc protrusion. Methods A total of 120 male rats were randomly divided into blank control (control) group, model group. Sham-operation(sham)group, and acupuncture group (n = 30) which were further divided into 7-days (d) and 14-d subgroups. Rats in the acupuncture group were treated with balance acupuncture of "Back Pain" point (the midpoint between two eyes) and "Hip Pain"point (the midpoint between the acromial process and the axillary furrow). Thermal pain threshold was detected by using radiant heat detector. Plasma p-EP and ACTH levels were determined by radioimmunoassay. Results Compared with the control group and pre-operation and sham group, the thermal pain reaction was increased significantly in the model group (P0. 05). Conclusion Balance acupuncture treatment can lower plasma ACTH level in lumbar disc herniation rats, which may contribute to its effect in easing lumbar disc herniation pain in clinic practice.%目的:初步探求平衡针治疗腰椎间盘突出神经根压迫症状的作用机制.方法:将SD雄性大鼠随机分为空白组、假手术组、模型组、治疗组,每组30只,各组中又分为7d取材组和14d取材组各15只.用肠线环扎L4神经根造模.治疗组针刺“腰痛穴”“臀痛穴”,每日2次.用热痛测试仪检测各组大鼠造模前及造模后第4、7、10、14天的缩爪潜伏期,采用放射免疫分析法测定血浆β-内啡肽(EP)及促肾上腺皮质激素(ACTH)的变化.结果:模型组大鼠痛敏现象明显增强(P<0.05),血浆β-EP、ACTH的含量呈增高趋势;经过平衡针治疗,治疗组痛敏现象至治疗第10天起较模型组明显降低(P<0.05),血浆中β-EP的含量第7天时就较模型组显著降低(P<0.05),

  15. 快眼动睡眠剥夺对抑郁模型大鼠行为学及血清COR和ACTH的影响%The effects of REM sleep deprivation on praxiology and COR/ACTH in rats treated with chronic stress

    Institute of Scientific and Technical Information of China (English)

    刘海静; 何新芳; 陈兴华

    2009-01-01

    目的 通过观察抑郁模型大鼠剥夺快速动眼相睡眠后的行为学及血清皮质醇(COR)和促肾上腺皮质激素(ACTH)含量的变化,探讨睡眠剥夺的抗抑郁机制.方法 30只成年雌雄各半的SD大鼠随机分为健康对照组、抑郁模型组和睡眠剥夺组,每组10只.后2组采用孤养和长期不可预见的中等强度应激制作大鼠抑郁模型,睡眠剥夺组又采用小平台水环境法进行72 h快眼动睡眠剥夺,比较各组大鼠自主活动及血清COR和ACTH含量的变化.结果 抑郁模型组大鼠血清COR和ACTH含量均较健康对照组有显著升高(P<0.01),而睡眠剥夺组大鼠较抑郁模型组血清中COR和ACTH含量均显著下降(P<0.01),而与健康对照组无显著差异(P>0.05).结论 快眼动睡眠剥夺可逆转抑郁模型大鼠的抑郁样行为,其抗抑郁作用与其对下丘脑-垂体-肾上腺系统(HPA轴)的调整相关.

  16. Effects of Suyu capsule on ACTH, cortisol in plasma and immune function in depression rats%苏郁胶囊对抑郁模型大鼠血浆ACTH、皮质醇和免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    钟晓明; 毛庆秋; 黄真; 魏佳平; 梁泽华

    2006-01-01

    目的:研究苏郁胶囊对慢性应激抑郁模型大鼠的血浆促肾上腺皮质激素(ACTH)、皮质醇及免疫功能的影响.方法:将72只成年SD雄性大鼠随机分为正常组、模型组、苏郁胶囊高、中、低剂量组(22.8,11.4,5.7 g·kg-1)及氯米帕明组(0.02 g·kg-1).采用长期不可预见性中等强度应激结合孤养造成大鼠抑郁模型,造模同时各组ig给药,正常组及模型组给予等量的生理氯化钠溶液,qd,共21 d.测定各组大鼠体重变化、糖水消耗量及强迫游泳不动时间;采用放射免疫方法检测大鼠血浆ACTH和皮质醇含量;测定各组大鼠的淋巴细胞增殖及自然杀伤细胞(NK)活性.结果:与模型组比较,苏郁胶囊高剂量组的体重增长明显加快(P<0.05),游泳不动时间明显缩短(P<0.05);苏郁胶囊3个剂量组的总液体消耗量及糖水消耗量均明显增加(P<0.01或P<0.05);高、中剂量组血浆中ACTH和皮质醇含量均明显降低(P<0.01或P<0.05),脾淋巴细胞增殖和NK细胞杀伤活性显著增加(P<0.01或p<0.05).结论:苏郁胶囊具有抗抑郁作用,其作用机制可能与抑制神经内分泌异常改变及促进机体的免疫机能相关.

  17. Effect of preoperative nursing care on the negative mood of patients with AIMAH%术前护理干预对ACTH-非依赖性双侧肾上腺大结节增生症腹腔镜手术患者负性情绪的影响

    Institute of Scientific and Technical Information of China (English)

    武晓

    2012-01-01

    目的 探讨护理干预减轻ACTH-非依赖性双侧肾上腺大结节增生症(AIMAH)患者负性情绪的效果.方法 对40例预行腹腔镜手术治疗的(AIMAH)患者,应用术前健康教育、心理干预等措施进行干预,采用焦虑自评量表(SAS)和抑郁自评量表(SDS)在干预前后进行心理评估,并测定睡眠时间.结果 40例AIMAH患者入院初期均存在不同程度的消极情绪.实施护理干预后,患者SAS及SDS得分较干预前明显降低[(40.68±7.42)分比(51.56±10.16)分;(42.63±7.98)分比(58.64±11.14)分],干预前后比较,差异有统计学意义(t=4.212,P<0.05);实施护理干预后,患者睡眠时间延长[(6.96±0.42)h比(5.82±0.31)h].干预前后比较,差异有统计学意义(t=3.305,P<0.01).结论 对AIMAH患者实施有针对性的护理干预,可减轻患者焦虑、抑郁、恐惧等负性情绪,可提高患者的依从性,使其更好的配合治疗,促进其早日康复.%Objective To discuss the effect of preoperative nursing care on the patients with AIMAH.Methods Totals of 40 patients with AIMAH received the nursing intervention such as health education,psychological nursing,etc.They were investigated with SAS and SDS,and sleep time was measured before and after the intervention.Results Totals of 40 patients were in different degree of negative mood when enrolled to hospital.Before and after nursing intervention,the SAS and SDS scores of patients were lower [(51.56±10.16) vs (40.68±7.42),(58.64±11.14) vs (42.63±7.98)],and their sleep time was extended [(5.82±0.31 ) h vs (6.96±0.42) h],and the difference was statistically significant ( t=4.212,3.305,respectively ;P<0.05).Conclusions Nursing intervention for the patients with AIMAH is very useful,it can improve the patients' negative mood,compliance,and promote their recovery.

  18. Neurotrophic ACTH4-9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis

    OpenAIRE

    Gispen, W. H.; Duckers, H.J.; van Dokkum, R.P.; Verhaagen, J; Luijtelaar, E.L.; Coenen, A.M.; Lopes da Silva, F.H.

    1998-01-01

    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 famil...

  19. Neurotrophic ACTH4-9 analogue therapy normalizes electroencephalographic alterations in chronic experimental allergic encephalomyelitis

    NARCIS (Netherlands)

    Gispen, W.H.; Duckers, H.J.; Dokkum, R.P. van; Verhaagen, J.; Luijtelaar, E.L.; Coenen, A.M.; Lopes da Silva, F.H.

    1998-01-01

    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 de

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

    Science.gov (United States)

    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.

  1. CHANNEL CATFISH, ICTALURUS PUNCTATUS, LEUKOCYTES SECRETE IMMUNOREACTIVE ADRENAL CORTICOTROPIN HORMONE (ACTH). (R823881)

    Science.gov (United States)

    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...

  2. Amygdaloid lesions block the effect of neuropeptides (vasopressin, ACTH4–10) on avoidance behavior

    NARCIS (Netherlands)

    Wimersma Greidanus, T.B. van; Croiset, G.; Bakker, E.; Bouman, H.

    1979-01-01

    Lesions in the amygdaloid complex result in an increased activity of rats in open field behavior in that generally more exploration and rearing is observed as compared with sham-operated animals. No effect of the lesion was observed on acquisition and extinction of an active avoidance response, but

  3. Molecular pharmacology of cell receptors for cardiac glycosides, opiates, ACTH and ion channel modulators

    Energy Technology Data Exchange (ETDEWEB)

    Hnatowich, M.R.

    1986-01-01

    The influence of light and oxygen on molecular interactions between the artificial food dye, erythrosine (ERY), and (/sup 3/H)ouabain ((/sup 3/H)OUA) binding sites on (Na/sup +/ + K/sup +/)-ATPase in rat brain and guinea pig heart was investigated. Putative endogenous digitalis-like factors (DLF's) were studied in four in vitro assays for cardiac glycosides. (/sup 3/H)Etorphine binding was characterized in rat brain homogenates, depleted of opioids, from animals acutely and chronically treated with morphine and naloxone, and either unstressed or cold-restraint-stressed. Binding sites for the ion channel modulators (/sup 3/H)verapamil ((/sup 3/H)VER) and (/sup 3/H) phencyclidine ((/sup 3/H)PCP) were characterized in rat brain.

  4. Neurotrophic peptide ACTH-(4–10) permits glucocorticoid-facilitated retention of acquired immobility response of hypophysectomized rats

    NARCIS (Netherlands)

    Kock, S. de; Kloet, E.R. de

    1987-01-01

    The Porsolt swimming test, which was originally designed as an experimental model to screen potential antidepressants demands that rats be forced to swim for 15 min in a narrow cylinder. Twenty four hours later they are retested for 5 min during which they stay immobile for approximately 70% of the

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

    Science.gov (United States)

    2015-09-30

    National Marine Mammal Foundation, USA), Dr. Bjarne Styrishave (Copenhagen University, Denmark), and Dr. Andrew J. Wright (George Mason University, USA...using skin samples collected from bottlenose dolphins (Tursiops truncatus). The dolphins will be sampled as part of an ongoing out-of water stress test ...and stress hormones study conducted by Dr. Dorian Houser in collaboration with the U.S. Navy Marine Mammal Program (MMP) under ONR project

  6. Permanent upregulation of hippocampal mineralocorticoid receptors after neonatal administration of ACTH-(4-9) analog ORG 2766 in rats

    NARCIS (Netherlands)

    Nyakas, C; Felszeghy, K; Bohus, B; Luiten, PGM

    1997-01-01

    The development of brain corticosteroid receptors may be permanently modified by perinatal hormone treatments, in particular by hormones of the hypothalamic-pituitary-adrenal axis. Changes in binding characteristics of corticosteroid receptors were investigated in rats treated subcutaneously with 1

  7. The effect of isoflurane anaesthesia and vasectomy on circulating corticosterone and ACTH in BALB/c mice

    DEFF Research Database (Denmark)

    Jacobsen, Kirsten Rosenmaj; Kalliokoski, Otto; Teilmann, Anne Charlotte;

    2012-01-01

    The use of blood corticosterone and faecal corticosterone metabolites as biomarkers of post-surgical stress and pain in laboratory animals has increased during the last decade. However, many aspects of their reliability in laboratory mice remain uninvestigated. This study investigated serum...... compared to anaesthetised mice not treated with dexamethasone. Thus, dexamethasone effectively inhibited the corticosterone response in the anaesthetised-only mice, but not in the mice subjected to surgery. In conclusion, both isoflurane anaesthesia and vasectomy during isoflurane anaesthesia resulted...... in an increase in serum glucocorticoids, but the negative feedback mechanism of newly operated mice, was altered. This may have consequences for the interpretation of glucocorticoids measurements as a biomarker of post-surgical stress in mice....

  8. Lower birth weight and attenuated adrenocortical response to ACTH in offspring from sows that orally received cortisol during gestation

    NARCIS (Netherlands)

    Kranendonk, G.; Hopster, H.; Fillerup, M.; Ekkel, E.D.; Mulder, E.J.H.; Wiegant, V.M.; Taverne, M.A.M.

    2006-01-01

    Prenatal stress is known to affect several offspring characteristics, but its effects depend among other factors on the period of gestation in which it is applied. In the present study, oral administration of hydrocortisone-acetate (HCA) was used to elevate cortisol concentrations in pregnant sows t

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

    Science.gov (United States)

    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.

  10. Exponentially Distributed Outages of Decreased ACTH and Cortisol Responses to Stress in Healthy Adults with Childhood Maltreatment

    Directory of Open Access Journals (Sweden)

    Geetha. T

    2014-11-01

    Full Text Available Preclinical research findings suggest that exposure to stress and concomitantly hypothalamus-pituitary-adrenal (HPA axis activation during early development can have permanent and potentially deleterious effects. A history of early-life abuse or neglect appears to increase risk for mood and anxiety disorders. Abnormal HPA response to stress challenge has been reported in adult patients with Major Depressive Disorder and PostTraumatic Stress Disorder. This paper discussed the constant stress level of adult patients with times to damage of stress effect and recoveries. Also In adults without diagnosable psychopathology, childhood maltreatment is associated with diminished HPA axis response to a psychosocial stressor.

  11. ACTH deficiency, higher doses of hydrocortisone replacement, and radiotherapy are independent predictors of mortality in patients with acromegaly.

    LENUS (Irish Health Repository)

    Sherlock, M

    2009-11-01

    A number of retrospective studies report that patients with acromegaly have increased morbidity and premature mortality, with standardized mortality ratios (SMR) of 1.3-3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or therapies such as surgery and radiotherapy. Pituitary radiotherapy and hypopituitarism have also been associated with an increased SMR.

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

    Science.gov (United States)

    2014-09-30

    SEP 2014 2. REPORT TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Validating the Novel Method of Measuring Cortisol...hours, in addition to other manipulations (e.g. blubber biopsies ). This process has shown to significantly raise both cortisol and aldosterone above

  13. alpha-Melanocyte-stimulating-hormone precursors in the pig pituitary

    DEFF Research Database (Denmark)

    Fenger, M

    1986-01-01

    The occurrence of intermediates from the processing of ACTH-(1-39) [adrenocorticotropic hormone-(1-39)] to alpha-melanocyte-stimulating hormone was investigated in normal pig pituitaries by the use of sensitive and specific radioimmunoassays for ACTH-(1-13), ACTH-(1-14), ACTH-(1-13)-NH2 and ACTH-(1...

  14. Cushing disease

    Science.gov (United States)

    ... much ACTH. ACTH stimulates production and release of cortisol, a stress hormone. Too much ACTH causes the adrenal glands to make too much cortisol. Cortisol is normally released during stressful situations. It ...

  15. Histological effects of co-administration of an ACTH((4-9)) analogue, ORG 2766, on cisplatin ototoxicity in the albino guinea pig

    NARCIS (Netherlands)

    Cardinaal, RM; de Groot, JCMJ; Huizing, EH; Veldman, JE; Smoorenburg, GF

    2000-01-01

    Cisplatin is one of the most potent antineoplastic drugs presently known, but its therapeutic efficacy is seriously limited by several side effects such as ototoxicity. Several compounds that are known for their nephroprotective effects also seem to reduce the incidence and severity of cisplatin-ind

  16. Somatotropin as the non-ACTH factor of anterior pituitary origin for the maintenance of enhanced aldosterone secretory responsiveness of dietary sodium restriction in chronically hypophysectomized rats

    NARCIS (Netherlands)

    Lee, T.C.; Wied, D. de

    1968-01-01

    Somatotropin treatment in chronically hypophysectomized, sodium-deprived rats effectively restored to treated animals the distinct and enhanced aldosterone secretory responsiveness of the adrenal which characterizes the adrenals of intact rats subjected to dietary sodium restriction, but absent in c

  17. 高位颈内静脉血ACTH/外周血ACTH对Cushing病的诊断价值研究

    Institute of Scientific and Technical Information of China (English)

    黄玮; 罗佐杰; 刘爱华

    2005-01-01

    Cushing病(Cushing disease,CD)与其他原因引起的库欣综合征(Cushing syndrome,CS)症状类似,病灶隐匿、且多为微腺瘤,往往术前难以准确地诊断。现代内分泌技术发展提高了CD定性与定位诊断的准确性,作者联合内分泌科、核医学科对25例确诊为CS的患者应用高位颈内静脉血样和大剂量地塞米松抑制试验(high dose suppress test,HDST)进行诊断试验,

  18. 胸腺类癌致异位ACTH综合征一例报告%Ectopic ACTH syndrome due to thymic carcinoid:one case report

    Institute of Scientific and Technical Information of China (English)

    毕宇芳; 孙首悦; 陈中元; 金晓龙; 王卫庆; 顾卫琼; 赵咏桔; 宁光

    2004-01-01

    @@ 异位ACTH综合征约占库欣综合征病因的10%左右,其中胸腺类癌所致者约占异源病因的2%~4%.1972年由Rosai和Higa首次报告以来,在英文文献中报告的共约有25例[1-7].现报告一例引起异位ACTH综合征的胸腺类癌.

  19. Imaging in Cushing's syndrome; Imagem em sindrome de Cushing

    Energy Technology Data Exchange (ETDEWEB)

    Sahdev, Anju; Evanson, Jane [St. Bartholomew' s Hospital, London (United Kingdom). Dept. of Diagnostic Imaging; Reznek, Rodney H. [St. Bartholomew' s Hospital, London (United Kingdom). Institute of Cancer. Cancer Imaging; Grossman, Ashley B. [St. Bartholomew' s Hospital, London (United Kingdom). Dept. of Endocrinology]. E-mail: anju.sahdev@bartsandthelondon.nhs.uk

    2007-11-15

    Once the diagnosis of Cushing's syndrome (CS) has been established, the main step is to differentiate between ACTH dependent and independent disease. In adults, 80% of CS is due to ACTH-dependent causes and 20% due to adrenal causes. ACTH-secreting neoplasms cause ACTH-dependent CS. These are usually anterior pituitary microadenomas, which result in the classic Cushing's disease. Non-pituitary ectopic sources of ACTH, such as a small-cell lung carcinoma or carcinoid tumours, are the source of the remainder of ACTH-dependent disease. In the majority of patients presenting with clinical and biochemical evidence of CS, modern non-invasive imaging can accurately and efficiently provide the cause and the nature of the underlying pathology. Imaging is essential for determining the source of ACTH in ectopic ACTH production, locating the pituitary tumours and distinguishing adrenal adenomas, carcinomas and hyperplasias. In our chapter we review the adrenal appearances in ACTH-dependent and ACTH-independent CS. We also include a discussion on the use of MRI and CT for the detection and management of pituitary ACTH secreting adenomas. CT of the chest, abdomen and pelvis with intravenous injection of contrast medium is the most sensitive imaging modality for the identification of the ectopic ACTH source and detecting adrenal pathology. MRI is used for characterising adrenal adenomas, problem solving in difficult cases and for detecting ACTH-secreting pituitary adenomas. (author)

  20. Synthesis and sup 11 C-labelling of the ACTH fragment analogue H-Met(O sub 2 )-Glu-His-Phe-D-Lys-Phe-OH (Org 2766) via its homocystine-containing precursor

    Energy Technology Data Exchange (ETDEWEB)

    Nispen, J.W. van; Janssen, W.P.A.; Melgers, P.A.T.A.; Janssen, P.S.L. (Organon Scientific Development Group, Oss (Netherlands)); Jansen, J.F.G.A.; Vaalburg, W. (Dept. of Nuclear Medicine, University Hospital Groningen, Groningen (Netherlands))

    1990-01-01

    The hexapeptide dimer (H-Hcy-Glu-His-Phe-D-Lys-Phe-OH){sub 2} was synthesized using solution methods and characterized. Its conversion into H-Met(O{sub 2})-Glu-His-Phe-D-Lys-Phe-OH, Org 2766, was studied on a small scale in as short a time as possible; reduction of the disulfide bond using Na/NH{sub 3}, reaction with CH{sub 3}I, oxidation with H{sub 2}O{sub 2} and catalyst and purification by HPLC were carried out starting with 2 mg of the dimer in a total preparation time of approximately 22 min, starting with the addition of CH{sub 3}I. The preparation of the {sup 11}C-labelled analogue was carried out by methylation with {sup 11}CH{sub 3}I. Restrictions imposed by working with carbon-11 will be discussed. (author).

  1. Recent developments in canine Cushing`s syndrome

    NARCIS (Netherlands)

    Galac, S.

    2010-01-01

    Cushing`s syndrome or hypercortisolism is one of the most common endocrinopathies in dogs. Besides the ACTH or pituitary-dependent and adrenal or ACTH-independent hypercortisolism, ectopic ACTH secretion and food-dependent hypercortisolism are described in the dog for the very first time. Ectopic AC

  2. A rare cause of Cushing's syndrome

    DEFF Research Database (Denmark)

    Folkestad, Lars; Andersen, Marianne Skovsager; Nielsen, Anne Lerberg;

    2014-01-01

    Excess glucocorticoid levels cause Cushing's syndrome (CS) and may be due to pituitary, adrenal or ectopic tumours. Adrenocorticotropic hormone (ACTH) levels are useful in identifying adrenal tumours. In rare cases, ACTH-producing phaeochromocytomas are the cause of CS. We present two cases of ACTH...

  3. Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism

    Directory of Open Access Journals (Sweden)

    Wen-Bo Wang

    2016-01-01

    Conclusions: The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.

  4. Immunoglobulin changes in boars exposed to administration of levamisole and exogenous adrenocorticotropic hormone

    Directory of Open Access Journals (Sweden)

    Bilandžić Nina

    2012-01-01

    Full Text Available The objective of this paper was to determine the effect of levamisole (LEV on immunoglobulin concentration in the serum of boars exposed to 3-day stress induced by exogenous ACTH. Boars were assigned to 4 groups (n=7. The first group received LEV for 3 days (2.5 mg/kg BW, the second group received ACTH (10 μg/kg BW for 3 days and the third group received LEV for 3 consecutive days and ACTH for the following 3 days (2.5 mg/kg BW; ACTH 10 μg/kg BW. The control group received saline solution during the 6 days. Concentrations of cortisol, total protein, globulin, albumin and immunoglobulin (IgG, IgA and IgM were determined during treatments and on the 16th day post-administration. Cortisol concentration was increased in both ACTH treated groups during all three days of administration and the day after the last ACTH treatment (p<0.05. ACTH increased total protein levels during the stress period and over the next 16 days (p<0.05. However, in the LEV+ACTH group total protein levels were elevated only on day 1 and 2 of ACTH injection (p<0.05 and after the end of treatment on day 11 and 22 (p<0.05. LEV stimulated the increase of protein concentrations compared to control values after LEV treatment, on days 5, 14, 18 and 22 (p<0.05. Serum albumins were not affected by LEV or ACTH treatment. Globulin concentrations were increased throughout and on the 16th day after administration of ACTH in the ACTH and LEV+ACTH groups (p<0.05. Globulin concentrations did not differ between LEV and control groups of boars. ACTH treatment elevated serum IgG concentration during the stress period (p<0.05 and over the next 16 days (p<0.05. However, in the LEV+ACTH group of boars, IgG levels were elevated on days 1 and 3 after ACTH injection (p<0.05 and days 1 and 5 in the post-treatment period (p<0.05. LEV had no impact on IgG levels compared to the control boars. However, increased IgA concentrations in boars treated with LEV were determined on day 2 (p<0.05 and day 11 (p

  5. Effects of intracerebroventricular injection of histamine and related compounds on corticosterone release in rats.

    OpenAIRE

    Tsujimoto, S.; Okumura, Y.; Kamei, C.; Tasaka, K.

    1993-01-01

    1. The effects of intracerebroventricular (i.c.v.) injection of histamine and related compounds on plasma adrenocorticotrophic hormone (ACTH) and corticosterone concentrations were studied in conscious rats. 2. Histamine at doses of 5-20 micrograms kg-1 rapidly increased plasma ACTH and corticosterone concentrations almost simultaneously, and subsequent courses were also similar to each other. However, in the case of CRF-41 (i.v.), the plasma ACTH concentration first increased followed by an ...

  6. Evaluation of adrenocortical function in Florida manatees (Trichechus manatus latirostris).

    Science.gov (United States)

    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.

  7. Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in a Novartis-sponsored Study.

    Science.gov (United States)

    2016-10-10

    Cushing's Disease,; Acromegaly,; Neuroendocrine Tumors,; Pituitary Tumors; Ectopic ACTH Secreting (EAS) Tumors,; Dumping Syndrome,; Prostate Cancer,; Melanoma Negative for bRAF,; Melanoma Negative for nRAS

  8. Failure of adrenal corticosterone production in POMC-deficient mice results from lack of integrated effects of POMC peptides on multiple factors.

    Science.gov (United States)

    Karpac, Jason; Czyzewska, Katarzyna; Kern, Andras; Brush, Richard S; Anderson, Robert E; Hochgeschwender, Ute

    2008-08-01

    Production of corticosteroids from the adrenal gland is a multistep process in which corticosterone is enzymatically processed from its precursor cholesterol. The main hormone regulating the production of corticosterone is the proopiomelanocortin (POMC)-derived adrenocorticotropic hormone (ACTH). Adrenals of POMC-deficient (POMC(-/-)) mice do not produce corticosterone either at basal levels or in response to acute stimulation with ACTH. However, pharmacological amounts of ACTH delivered continuously elicit corticosterone production over time. To define the relative effects of ACTH on individual factors involved in corticosterone production, parameters of adrenal cholesterol metabolism and steroidogenesis were examined in POMC(-/-) mice compared with wild-type and ACTH-treated mutant mice. POMC(-/-) adrenals lack cholesterol esters (CE); adrenal CE is restored with ACTH treatment. However, discontinuation of ACTH treatment stops corticosterone production despite the presence of adrenal CE. Failure of corticosterone production by POMC(-/-) adrenals occurs despite the constitutive presence of transcripts of genes required for cholesterol metabolism and steroidogenesis. Levels of key proteins involved in selective cholesterol uptake and steroidogenesis were attenuated; ACTH treatment increased these protein levels, most significantly those of the receptor responsible for selective uptake of CE, scavenger receptor class B, type I (SR-BI). Our studies reveal that failure of corticosterone production of POMC(-/-) adrenal glands and its pharmacological reconstitution by ACTH are not mediated by any one individual protein, but rather as an integrated effect on multiple factors from import of the substrate cholesterol to its conversion to corticosterone.

  9. Pubertal Shifts in Adrenal Responsiveness to Stress and Adrenocorticotropic Hormone in Male Rats

    Science.gov (United States)

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

    2014-01-01

    Summary Studies have indicated significant pubertal-related differences in hormonal stress reactivity. We report here that prepubertal (30d) male rats display a more protracted stress-induced corticosterone response than adults (70d), 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 9.375 μg/kg of exogenous rat ACTH and measured their hormone levels 30 and 60 min 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 30 min time point. However, 60 min 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. PMID:24636511

  10. 重楼皂甙对急性吗啡耐受大鼠痛反应及海马ACTH和β-EP含量的影响%Effects of Rhizoma Paridis saponins on the pain threshold and Ir-ACTH and Ir-β-EP contents in hippocampus of acute morphine tolerant rats

    Institute of Scientific and Technical Information of China (English)

    王建; 黎海蒂; 徐海伟; 方勇飞; 龚发云; 李希成

    2000-01-01

    目的探讨大鼠急性吗啡镇痛耐受时,痛行为和海马ACTH和β-内啡肽(β-EP)含量变化及重楼皂甙对其影响.方法本实验采用大鼠急性吗啡镇痛耐受模型,运用热测痛法观察重楼皂甙对其痛阈的作用,并用放射免疫法测定海马ACTH和β-EP含量变化.结果在急性单次皮下注射盐酸吗啡(6 mg/kg)后,海马ACTH和β-EP含量升高,而当连续5次皮下注射盐酸吗啡(6 mg/kg,间隔2 h)后,海马ACTH和β-EP含量回降.重楼皂甙对这一回降过程有抑制作用,并增强吗啡对急性吗啡耐受大鼠痛阈的提高作用.结论重楼皂甙在吗啡急性耐受形成后可能有增强吗啡镇痛的作用,并可能通过影响脑内ACTH和β-EP等因素影响耐受形成.

  11. 短跑运动员比赛前后血清β-内啡肽、促肾上腺皮质激素和血清皮质醇的变化%Research on the Changes of β-endorphin, ACTH and Serum Cortisol of Sprinters before and after Competitions

    Institute of Scientific and Technical Information of China (English)

    谭永洁

    2006-01-01

    为了观察短跑运动员比赛前后血清β-内啡肽、促肾上腺皮质激素和血清皮质醇的变化.应用放射免疫分析法(RIA)检测100 m比赛前后专业组和业余组运动员血清β-内啡肽、促肾上腺皮质激素以及血清皮质醇含量.结果发现:100 m比赛前后专业组和业余组运动员血清β-内啡肽、促肾上腺皮质激素以及血清皮质醇含量均较安静状态增高,但专业组的增高幅度较业余组低.表明:运动锻炼可以提高运动员应激能力,减少应激损害,提高应变能力.

  12. Hyperadrenocorticism in a dog due to ectopic secretion of adrenocorticotropic hormone

    NARCIS (Netherlands)

    Galac, S; Kooistra, HS; Voorhout, G; van den Ingh, TSGAM; Mol, JA; van den Berg, G; Meij, BP

    2005-01-01

    Spontaneous hyperadrenocorticism in dogs is known to be the result of excessive secretion of adrenocorticotropic hormone (ACTH) by the pituitary gland or excessive autonomous glucocorticoid secretion by an adrenocortical tumor. Here, we report on an 8-year-old German shepherd dog in which ACTH-depen

  13. Disease: H01011 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ted adrenocorticotropic hormone deficiency (IAD) is a rare disease characterized by low plasma ACTH and cortisol...e TBX19 [HSA:9095] [KO:K10184] Low plasma ACTH [CPD:C02017] and cortisol [CPD:C00735] levels ICD-10: E23.6 M

  14. A novel homozygous insertion and review of published mutations in the NNT gene causing familial glucocorticoid deficiency (FGD)

    NARCIS (Netherlands)

    Jazayeri, Omid; Liu, Xuanzhu; van Diemen, Cleo C.; Bakker-van Waarde, Willie M.; Sikkema-Raddatz, Birgit; Sinke, Richard J.; Zhang, Jianguo; van Ravenswaaij-Arts, Conny M. A.

    2015-01-01

    Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder characterized by low levels of cortisol despite high adrenocorticotropin (ACTH) levels, due to the reduced ability of the adrenal cortex to produce cortisol in response to stimulation by ACTH. FGD is a heterogeneous disorder

  15. New developments in the medical treatment of Cushing's syndrome

    NARCIS (Netherlands)

    R. van der Pas (Rob); W.W. de Herder (Wouter); L.J. Hofland (Leo); R.A. Feelders (Richard)

    2012-01-01

    textabstractCushing's syndrome (CS) is a severe endocrine disorder characterized by chronic cortisol excess due to an ACTH-secreting pituitary adenoma, ectopic ACTH production, or a cortisol-producing adrenal neoplasia. Regardless of the underlying cause, untreated CS is associated with considerable

  16. [Corticotropic macroadenoma: clinical, hormonal, radiological and immunocytochemical study of 6 cases].

    Science.gov (United States)

    Maréchaud, R; Humbert, C; Bonneau, F; Saint-André, J P; Bataille, B; Fieuzal, S; Prono, C; Vandermarcq, P

    1993-01-01

    We report 6 cases of corticotroph macroadenomas which show heterogeneity of clinical and biological features (from Cushing's syndrome to silent adenoma) and heterogeneity of immunocytochemical staining. One patient reported on had skin hyperpigmentation and ACTH hypersecretion without clear abnormal adrenocortical function; we believe that this patient's plasma contained ACTH with very low bioactivity.

  17. A Vessel Class Comparison of Physiological, Affective State and Psychomotor Performance Changes in Men at Sea

    Science.gov (United States)

    1980-08-01

    are released in proportion to their rate of synthesis. Control of synthesis appears to be largely controlled by ACTH release from the adenohypophysis ...releasing hormone (CRF). This hormone stimulates release of ACTH from the adenohypophysis which, in turn, acts upon the adrenal cortex to stimulate

  18. Beclomethasone dipropionate enema in ulcerative colitis: Is it safe?

    Science.gov (United States)

    Luboshitzky, Rafael; Rachelis, Zoia; Nussensone, Elchanan; Ishay, Avraham

    2009-06-02

    Objective: To evaluate the pituitary-adrenal axis (PA axis) reserve in patients with ulcerative colitis (UC) treated with steroid enemas, we performed 1mug ACTH test.Methods: Patients with UC (n=8) given beclomethasone dipropionate enema (Betnesol) for 4 weeks. Fasting serum cortisol and the response at 30 and 60 minutes following an IV 1mug ACTH injection were determined after 2 weeks of Betnesol enemas. Patients were retested, one month after discontinuation of enemas.Results: Fasting and peak cortisol responses to ACTH were suppressed in six patients. Additional patient had suppressed fasting cortisol and another patient had blunted response to ACTH. One month off Betnesol enema, basal and peak cortisol response to ACTH were normal in all but one patient.Conclusion: Betnesol enemas are associated with severe suppression of the PA axis in almost all patients. Caution is required in patients with UC after withdrawal of rectal steroids as adrenal insufficiency can occur.

  19. Effects of Imipramine and Lithium on the Suppression of Cell Proliferation in the Dentate Gyrus of the Hippocampus in Adrenocorticotropic Hormone-treated Rats

    Directory of Open Access Journals (Sweden)

    Doi,Maho

    2010-08-01

    Full Text Available We examined the influence of chronic adrenocorticotropic hormone (ACTH treatment on the number of Ki-67-positive cells in the dentate gyrus of the hippocampus in rats. ACTH treatment for 14 days decreased the number of such cells. The administration of imipramine or lithium alone for 14 days had no effect in saline-treated rats. The effect of ACTH was blocked by the administration of imipramine. Furthermore, the coadministration of imipramine and lithium for 14 days significantly increased the number of Ki-67-positive cells in both the saline and ACTH-treated rats. The coadministration of imipramine and lithium normalized the cell proliferation in the dentate gyrus of the hippocampus in rats treated with ACTH.

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

    Science.gov (United States)

    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

  1. Noninvasive monitoring of adrenocortical function in captive jaguars (Panthera onca).

    Science.gov (United States)

    Conforti, Valéria A; Morato, Ronaldo G; Augusto, Anderson M; de Oliveira e Sousa, Lúcio; de Avila, David M; Brown, Janine L; Reeves, Jerry J

    2012-01-01

    Jaguars are threatened with extinction throughout their range. A sustainable captive population can serve as a hedge against extinction, but only if they are healthy and reproduce. Understanding how jaguars respond to stressors may help improve the captive environment and enhance their wellbeing. Thus, our objectives were to: (1) conduct an adrenocorticotrophic hormone (ACTH) challenge to validate a cortisol radioimmunoassay (RIA) for noninvasive monitoring of adrenocortical function in jaguars; (2) investigate the relationship between fecal corticoid (FCM) and androgen metabolite (FAM) concentrations in males during the ACTH challenge; and (3) establish a range of physiological concentrations of FCMs for the proposed protocol. Seven jaguars (3 M, 4 F) received 500 IU/animal of ACTH. Pre- and post-ACTH fecal samples were assayed for corticoid (M and F) and androgen metabolites (M) by RIA. Concentrations of FCMs increased (P80.01) after ACTH injection (pre-ACTH: 0.90 ± 0.12 µg/g dry feces; post-ACTH: 2.55 ± 0.25 µg/g). Considering pre- and post-ACTH samples, FCM concentrations were higher (P80.01) in males (2.15 ± 0.20 µg/g) than in females (1.30 ± 0.20 µg/g), but the magnitude of the response to ACTH was comparable (P>0.05) between genders. After ACTH injection, FAMs increased in two (of 3) males; in one male, FCMs and FAMs were positively correlated (0.60; P80.01). Excretion of FCMs was assessed in 16 jaguars (7 M, 9 F) and found to be highly variable (range, 80.11-1.56 µg/g). In conclusion, this study presents a cortisol RIA for monitoring adrenocortical function in jaguars noninvasively.

  2. Coordinate control of corticotropin, β-lipotropin, and β-endorphin release in mouse pituitary cell cultures

    Science.gov (United States)

    Allen, Richard G.; Herbert, Edward; Hinman, Michael; Shibuya, Haruo; Pert, Candace B.

    1978-01-01

    Hypothalamic extract stimulates the release of corticotropin (ACTH) and endorphins 2.5- to 30-fold in mouse pituitary tumor cell cultures (AtT-20/D16v line) and primary cell cultures from mouse anterior pituitary. ACTH and endorphin activities were measured by radioimmunoassay and immunoprecipitation. Pretreatment of tumor cell cultures with 1 μM dexamethasone reduced the stimulatory effect of the extract on release of ACTH and endorphins. Pretreatment of primary cell cultures with 10-6 M dexamethasone reduced the stimulatory effect of both vasopressin and the extract on the release of ACTH and endorphins. Release of ACTH and endorphin was coupled in both kinds of cultures in the basal, stimulated, and inhibited states. The molecular weight forms of ACTH and endorphin in tumor cell culture medium were analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Radioimmunoassay and immunoprecipitation show that the 13,000-dalton and 4500-dalton forms of ACTH were present in about equal amounts in medium from cultures incubated with or without hypothalamic extract for 15 min, 30 min, or 2 hr. Smaller amounts of the high molecular weight forms of ACTH (20,000- to 23,000-dalton and 31,000-dalton ACTH) were observed in the culture medium at these times. The predominant forms of endorphin released after 20 min or 3 hr of incubation had molecular weights of 31,000, 11,700 (β-lipotropic hormone-size material) and 3500 (β-endorphin-size material). No degradation of the forms of endorphin released into the culture medium was observed after incubating the culture medium for 1.5 hr in the absence of cells. The proportions of the different forms of endorphin and ACTH present in the culture medium resembles that seen in cell extracts. PMID:217008

  3. Adrenocorticotropin receptors: Functional expression from rat adrenal mRNA in Xenopus laevis oocytes

    Energy Technology Data Exchange (ETDEWEB)

    Mertz, L.M.; Catt, K.J. (National Inst. of Health, Bethesda, MD (United States))

    1991-10-01

    The adrenocorticotropin (ACTH) receptor, which binds corticotropin and stimulates adenylate cyclase and steroidogenesis in adrenocortical cells, was expressed in Xenopus laevis oocytes microinjected with rat adrenal poly(A){sup +} RNA. Expression of the ACTH receptor in individual stage 5 and 6 oocytes was monitored by radioimmunoassay of ligand-stimulated cAMP production. Injection of 5-40 ng of adrenal mRNA caused dose-dependent increases in ACTH-responsive cAMP production. Size fractionation of rat adrenal poly(A){sup +}RNA by sucrose density-gradient centrifugation revealed that mRNA encoding the ACTH receptor was present in the 1.1-to 2.0-kilobase fraction. These data indicate that ACTH receptors can be expressed from adrenal mRNA in Xenopus oocytes and are fully functional in terms of ligand specificity and signal generation. The extracellular cAMP response to ACTH is a sensitive and convenient index of receptor expression. This system should permit more complete characterization and expression cloning of the ACTH receptor.

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

    Science.gov (United States)

    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. Analyzing the activation of the melanocortin-2 receptor of tetrapods.

    Science.gov (United States)

    Dores, Robert M; Liang, Liang

    2014-07-01

    Following the biochemical characterization of the pituitary hormone, adrenocorticotropin (ACTH), in the 1950's, a number of structure/function studies were done which identifies two amino acid motifs in ACTH, the HFRW motif and KKRR motif, as critical for the activation of the "ACTH" receptor on adrenal cortex cells. In the 1990's the "ACTH" receptor was identified as a member of the melanocortin receptor gene family, and given the name melanocortin-2 receptor (MC2R). Since that time a number of studies on both tetrapod and teleost MC2R orthologs have established that these orthologs can only be activated by ACTH, but not by any of the MSH-sized melanocortin ligands, and these orthologs require interaction with the melanocortin-2 receptor accessory protein (MRAP) for functional expression. This review summarizes recent structure/function studies on human ACTH, and points out the importance of the GKPVG motif in ACTH for the activation of the receptor. In this regard, a multiple-step model for the activation of tetrapod and teleost MC2R orthologs is presented, and the evolution of gnathostome MC2R ligand selectivity and the requirement for MRAP interaction is discussed in light of a recent study on a cartilaginous fish MC2R ortholog. This review contains excerpts from the Gorbman/Bern Lecture presented at the Second Meeting of the North American Society for Comparative Endocrinology (NASCE).

  6. Direct measurement of the precursors of adrenocorticotropin in human plasma by two-site immunoradiometric assay

    Energy Technology Data Exchange (ETDEWEB)

    Crosby, S.R.; Stewart, M.F.; Ratcliffe, J.G.; White, A.

    1988-12-01

    An immunoradiometric assay (IRMA) for the direct measurement of the precursors of ACTH in unextracted human plasma has been developed and evaluated clinically in normal subjects and patients with disorders of the hypothalamic-pituitary-adrenal axis. The IRMA is based on an iodinated monoclonal antibody to ACTH and a monoclonal antibody to gamma MSH coupled to Sephacryl S300. The assay detects only peptides containing both epitopes, i.e. POMC (31K) and pro-ACTH (22K). The reference standard was partially purified POMC from culture medium of human corticotroph adenoma cells. The detection limit (greater than +2.5SD of the 0 standard) was 2.0 pmol/L and the within-assay coefficient of variation was less than 10% between 29 and 2600 pmol/L. Plasma concentrations of ACTH precursor peptides in 11 normal subjects sampled at 0930 h ranged from 5-34 pmol/L. The concentrations in the patient groups studied were: 260-2300 pmol/L in 5 patients with the ectopic ACTH syndrome associated with small cell lung cancer, less than 2.0-104 pmol/L in 10 patients with pituitary-dependent Cushing's disease, 23 pmol/L in a patient with Nelson's syndrome, and 3.0-230 pmol/L in 5 patients with Addison's disease. We conclude that this IRMA offers a simple and reliable method for measuring ACTH precursors in unextracted plasma. The proportionately greater elevation of ACTH precursors compared to ACTH in patients with the ectopic ACTH syndrome associated with small cell lung cancer but not in pituitary-dependent Cushing's syndrome, suggests that this assay may be clinically useful.

  7. Adrenocorticotropin hormone 1-39 promotes proliferation and differentiation of oligodendroglial progenitor cells and protects from excitotoxic and inflammation-related damage.

    Science.gov (United States)

    Benjamins, Joyce A; Nedelkoska, Liljana; Lisak, Robert P

    2014-10-01

    Oligodendroglia (OL) are highly susceptible to damage and, like neurons, are terminally differentiated. It is important to protect OL precursors (OPC) because they are reservoirs of differentiating cells capable of myelination following perinatal insult and remyelination in white matter diseases, including multiple sclerosis (MS). Patients with relapsing-remitting MS are commonly treated with high-dose corticosteroids (CS) when experiencing an exacerbation. Adrenocorticotropin hormone (ACTH), a primary component of another approved MS exacerbation treatment, is a melanocortin peptide that stimulates production of CS by the adrenals. Melanocortin receptors are also found in the central nervous system (CNS) and on immune cells. ACTH is produced within the CNS and may have CS-independent effects on glia. We found that ACTH 1-39 stimulated proliferation of OPC, and to a lesser extent astroglia (AS) and microglia (MG), in rat glial cultures. ACTH accelerated differentiation of PDGFRα(+) OPC to a later stage marked by galactolipid expression and caused greater expansion of OL myelin-like sheets compared with untreated cells. Protective effects of ACTH on OPC were assessed by treating cultures with selected toxic agents, with or without ACTH. At 200 nM, ACTH protected OPC from death induced by staurosporine, glutamate, NMDA, AMPA, kainate, quinolinic acid, H2 O2 , and slow NO release, but not against kynurenic acid or rapid NO release. These agents and ACTH were not toxic to AS or MG. Our findings indicate that ACTH 1-39 provides benefits by increasing the number of OPC, accelerating their development into mature OL, and reducing OPC death from toxic insults.

  8. Acute inhibition of corticosteroidogenesis by inhibitors of calmodulin action.

    Science.gov (United States)

    Carsia, R V; Moyle, W R; Wolff, D J; Malamed, S

    1982-11-01

    To identify the possible role of calmodulin in ACTH function, we tested the ability of chlorpromazine (CP) and other calmodulin antagonists to inhibit steroidogenesis of isolated adrenocortical cells of the rat. CP reversibly inhibited maximal ACTH-induced corticosterone (B) production. The presence of the drug did not alter the ED50 of ACTH stimulation (3.2 X 10(3) pg/ml), suggesting that it inhibited ACTH-induced steroidogenesis in a noncompetitive manner. The CP concentration required for half-maximal inhibition was 8.2 microM, a value close to the dissociation constant of the CP-calmodulin complex (5.3 microM). Concentrations greater than 40 microM resulted in complete inhibition. Similar concentrations of CP inhibited ACTH-induced cAMP accumulation in a dose-dependent manner, indicating an effect of the drug on early events in ACTH action. In addition, CP also apparently acted at a site distal to the point of cAMP formation, as shown by the finding that it inhibited cAMP-induced B production. CP inhibition of ACTH-induced B production was independent of the Ca2+ concentration, suggesting that the drug did not compete with Ca2+ directly. Concentrations of CP greater than 20 microM inhibited protein synthesis as measured by leucine incorporation into cellular proteins. Thus, although the inhibitory effect of high concentrations of CP on steroidogenesis might be explained by an effect on protein synthesis, the inhibition seen at 10 microM appeared to be independent of protein synthesis. Other antagonists of calmodulin action inhibited maximal ACTH-induced B production with the following relative potencies: trifluoperazine greater than CP greater than haloperidol greater than chlordiazepoxide. This order is similar to that reported for inhibition of calmodulin-activated phosphodiesterase and for binding to calmodulin. These findings suggest that calmodulin may modulate the effect of ACTH on steroidogenesis at multiple sites.

  9. Participation of endocannabinoids in rapid suppression of stress responses by glucocorticoids in neonates.

    Science.gov (United States)

    Buwembo, A; Long, H; Walker, C-D

    2013-09-26

    In adult rodents, endocannabinoids (eCBs) regulate fast glucocorticoid (GC) feedback in the hypothalamus-pituitary adrenal (HPA) axis, acting as retrograde messengers that bind to cannabinoid receptors (CB1R) and inhibit glutamate release from presynaptic CRH neurons in the paraventricular nucleus of the hypothalamus (PVN). During the first two weeks of life, rat pups exhibit significant CRH and ACTH responses to stress although the adrenal GC output remains reduced. At the same time, pups also display increased sensitivity to GC feedback, but it is unclear whether eCBs play a role in mediating fast GC feedback in neonatal life. In our studies, we examined the role of eCBs in the rapid suppression of anoxia-induced ACTH release and determined whether eCB action could be modulated by the levels of circulating GCs present at the time of stress. PND8 pups were subjected to 3-min anoxia with AM251, a CB1R blocker, injected 30 min prior to stress onset. The effects of either metyrapone (MET) (a steroidogenic 11 beta-hydroxylase blocker) or methylprednisolone (PRED) (a synthetic GC) pretreatment on AM251 effect and the stress response were evaluated. Treatment with AM251 before stress onset tended to increase overall ACTH and CORT secretion, and also delayed the return to baseline ACTH. The AM251 effect on ACTH in PND8 pups was lost in MET-treated pups, who exhibited high basal and stimulated ACTH release and no CORT response to stress. Methylprednisolone suppressed ACTH stress responses although AM251 still delayed restoration of ACTH levels to the baseline. This suggests that the eCB effect on ACTH secretion in neonates is most evident when there is a dynamic fluctuation of corticosterone levels. Interestingly, AM251 increased basal and stimulated corticosterone secretion in all treatments including MET, suggestive of a direct action of CB1R blockade on adrenal steroidogenesis.

  10. Electroacupuncture activates corticotrophin-releasing hormone-containing neurons in the paraventricular nucleus of the hypothalammus to alleviate edema in a rat model of inflammation

    Directory of Open Access Journals (Sweden)

    Berman Brian M

    2008-05-01

    Full Text Available Abstract Background Studies show that electroacupuncture (EA has beneficial effects in patients with inflammatory diseases. This study investigated the mechanisms of EA anti-inflammation, using a rat model of complete Freund's adjuvant (CFA-induced hind paw inflammation and hyperalgesia. Design Four experiments were conducted on male Sprague-Dawley rats (n = 6–7/per group. Inflammation was induced by injecting CFA into the plantar surface of one hind paw. Experiment 1 examined whether EA increases plasma adrenocorticotropic hormone (ACTH levels. Experiments 2 and 3 studied the effects of the ACTH and corticotropin-releasing hormone (CRH receptor antagonists, ACTH(11–24 and astressin, on the EA anti-edema. Experiment 4 determined whether EA activates CRH neurons in the paraventricular nucleus of the hypothalammus. EA treatment, 10 Hz at 3 mA and 0.1 ms pulse width, was given twice for 20 min each, once immediately post and again 2 hr post-CFA. Plasma ACTH levels, paw thickness, and paw withdrawal latency to a noxious thermal stimulus were measured 2 h and 5 h after the CFA. Results EA significantly increased ACTH levels 5 h (2 folds after CFA compared to sham EA control, but EA alone in naive rats and CFA alone did not induce significant increases in ACTH. ACTH(11–24 and astressin blocked EA anti-edema but not EA anti-hyperalgesia. EA induced phosphorylation of NR1, an essential subunit of the N-methyl-D-aspartic acid (NMDA receptor, in CRH-containing neurons of the paraventricular nucleus. Conclusion The data demonstrate that EA activates CRH neurons to significantly increase plasma ACTH levels and suppress edema through CRH and ACTH receptors in a rat model of inflammation.

  11. Metabolic complications of endogenous Cushing: patient selection for screening

    Directory of Open Access Journals (Sweden)

    Zh E Belaya

    2013-03-01

    Full Text Available Aims: this study evaluates the most common associations of symptoms and complications in patients with Cushing’s syndrome (CS in order to choose a potential population to be screened for CS and estimates the diagnostic accuracy of first line screening tests (cortisol, ACTH to differentiate ACTH-ectopic CS from Cushing’s disease. Materials and Methods: The clinical data of 259 patients with proven CS during 2001–2011 was analyzed. The clinical presentations of 197 patients (159 Cushing’s disease, 28 ACTH-ectopic CS and 10 cases of benign cortisol-secreting adrenal adenoma were compared according to the cause of hypercortisolism. ROC-analysis was performed to estimate the diagnostic accuracy of the first line tests (cortisol, ACTH to suggest ACTH-ectopic CS. A threshold for the test with the highest area under the curves was chosen based on the maximum sum of the sensitivity and specificity. Results: The most frequent complaints were related to fatigue, muscle weakness, weight gain and changes in appearance (facial plethora and fullness, striae. Among the complications of CS the most frequent were being overweight or obese (71%, hypertension (63%, dislipoproteinemia (41%, low traumatic fractures (43% and steroid-induced diabetes (31%. In women, 16% were older than 50, in those who were younger amenorrhea was registered in 43%. The patients with ACTH-ectopic CS had higher rate of low traumatic fractures (p=0.04, increased serum late-night cortisol, 24 hours urinary free cortisol, morning and evening ACTH and lower levels of potassium (p<0.01 for all parameters. Plasma late-night ACTH measurements showed the highest AUC (0,811 (95% CI 0,712–0,909 to differentiate ACTH-ectopic CS from Cushing’s disease. A cut off value of 108.9 pg/ml for late-night ACTH yielded a sensitivity of 60,7% and a specificity of 79%. Conclusions: patients with a coexistence of obesity, muscle weakness, fatigue, some components of metabolic syndrome and especially

  12. Complete adrenocorticotropin deficiency after radiation therapy for brain tumor with a normal growth hormone reserve

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Haruna; Yoshioka, Katsunobu; Yamagami, Keiko [Osaka City General Hospital (Japan)] (and others)

    2002-06-01

    A 34-year-old man with neurofibromatosis type 1, who had received radiation therapy after the excision of a brain tumor 5 years earlier, was admitted to our hospital with vomiting and weight loss. Cortisol and adrenocorticotropin (ACTH) were undetectable before and after administration of 100 {mu}g corticotropin releasing hormone. The level of growth hormone without stimulation was 24.7 ng/ml. We diagnosed him to have complete ACTH deficiency attributable to radiation therapy. This is the first known case of a patient with complete ACTH deficiency after radiation therapy and a growth hormone reserve that remained normal. (author)

  13. Hormonal secretion and quality of life in Nelson syndrome and Cushing disease after long acting repeatable octreotide: a short series and update.

    Science.gov (United States)

    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. Concentração plasmática do hormônio adrenocorticotrófico de parturientes submetidas a método não farmacológico de alívio da ansiedade e dor do parto Concentración de la hormona adrenocorticotrófica en parturientas sometidas a un método no farmacológico de alivio de ansiedad y el dolor durante el parto Corticotrophin hormone serum levels of parturients submitted to nonpharmacologic anxiety and pain relief method during labor

    Directory of Open Access Journals (Sweden)

    Nilza Alves Marques Almeida

    2005-04-01

    Full Text Available Objetivo: analisar os níveis séricos do hormônio adrenocorticotrófico (ACTH e a correlação entre esses níveis, a ansiedade e a dor na parturição. Dezessete parturientes (grupo controle - GC receberam assistência de enfermagem de rotina, e dezenove (grupo experimental - GE foram estimuladas e orientadas a realizar técnicas de respiração e relaxamento. Os níveis plasmáticos do ACTH, o traço e estado de ansiedade e a intensidade de dor foram avaliados. Os níveis de ACTH foram baixos no início do trabalho de parto, com pico no final e regressão no pós-parto imediato, sem diferença estatisticamente significativa entre os grupos. A redução do ACTH com alívio parcial do estresse do GE, sugere a interferência das técnicas de respiração e relaxamento. Os níveis do ACTH, não se correlacionaram à ansiedade e à dor, em ambos os grupos.La finalidad de este estudio fue analizar los niveles séricos de la hormona adrenocorticotrófica (ACTH, la correlación entre esos niveles, la ansiedad y el dolor en el parto. Diecisiete parturientas (grupo control - GC recibieron atención de enfermería de rutina y diecinueve (grupo experimento - GE fueron preparadas y orientadas a realizar técnicas de respiración y relajación. Los niveles de la ACTH, el trazo y estado de ansiedad y la intensidad del dolor fueron evaluados. Los niveles de la ACTH fueron bajos en el inicio del trabajo de parto, con elevación en el final y regresión en el postparto inmediato, sin diferencia estadísticamente significativa entre los grupos. La reducción de la ACTH con alivio parcial del stress del GE, sugiere la interferencia de las técnicas de respiración y relajación. Los niveles de la ACTH no se correlacionaron ni con la ansiedad ni con el dolor, en ambos grupos.This study aimed to analyze the plasma ACTH levels and the correlation between the ACTH levels and pain and anxiety during the parturition. Seventeen parturients received routine nursing

  15. Reversible posterior encephalopathy syndrome associated with micronodular adrenocortical disease and Cushing syndrome.

    Science.gov (United States)

    Lodish, Maya; Patronas, Nicholas J; Stratakis, Constantine A

    2010-01-01

    We report a 6-year-old girl with ACTH-independent Cushing syndrome secondary to bilateral adrenal hyperplasia; she presented with hypertension and seizures, and magnetic resonance imaging shows changes consistent with posterior reversible encephalopathy syndrome.

  16. Medline Plus

    Full Text Available ... stimulates breast tissue in nursing mothers to produce milk ACTH (adrenocorticotropic hormone) - causes the adrenal glands to ... less urine Oxytocin - initiates labor, uterine contractions and milk ejection in mothers

  17. Prognosis of Cyclic Vomiting Syndrome

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2016-03-01

    Full Text Available Investigators from Teikyo University School of Medicine, Tokyo, Japan, evaluated the clinical features, prognosis, and prophylaxis of cyclic vomiting syndrome and the relationship between the syndrome and levels of adrenocorticotropic/antidiuretic hormones (ACTH/ADH.

  18. Whole blood samples for adrenocorticotrophic hormone measurement can be stored at room temperature for 4 hours

    DEFF Research Database (Denmark)

    Christensen, Mette; Madsen, Rikke Fogt; Møller, Line Rosengreen

    2016-01-01

    INTRODUCTION: The aim of this study was to investigate and compare the stability of adrenocorticotrophic hormone (ACTH) in whole blood stored on ice and at room temperature for up to 48 hours. This study differs from previous studies by a larger data material. MATERIALS AND METHODS: EDTA......-blood samples from 30 patients were collected, aliquoted and stored on ice or at room temperature for 0, 2, 4, 24, or 48 h before centrifugation, and the plasma was stored frozen until analysis. All samples were analyzed using an automated electrochemiluminescence immunoassay on cobas 6000 e601. The change...... in ACTH concentration was illustrated as ACTH recovery compared to standard conditions defined as samples stored immediately on ice, centrifuged and plasma frozen within 1 h. A change in ACTH concentration of more than 10% was considered to be of clinical relevance. RESULTS: The results showed...

  19. Disease: H00256 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ndromes. Endocr Dev 13:99-116 (2008) PMID:17161331 Metherell LA, Chan LF, Clark AJ The genetics of ACTH resistance syndromes. Best Pract Res Clin Endocrinol Metab 20:547-60 (2006) ...

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

    Science.gov (United States)

    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...

  1. Excessive or unwanted hair in women

    Science.gov (United States)

    ... present) 17-hydroxyprogesterone blood test ACTH stimulation test Treatment Hirsutism is generally a long-term problem. There are many ways to remove or treat unwanted hair. Some treatment effects last longer than others. Medicines. Drugs such ...

  2. Hypokalemia associated with a solitary pulmonary nodule

    Science.gov (United States)

    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

  3. Addison’s Disease Patient Presenting with Cushing’s Syndrome Findings

    Directory of Open Access Journals (Sweden)

    Aslı Doğruk Ünal

    2013-03-01

    Full Text Available A 24-year-old man with Addison’s disease, who was receiving replacement therapy with prednisolone, was admitted to our hospital due to findings of both hypocortisolism and hypercortisolism. Plasma adrenocorticotropic hormone (ACTH was found to be high during and after withdrawal of prednisolone therapy. ACTH was not suppressed with 2 mg or 8 mg of dexamethasone. Gadolinium-diethylene triamine penta-acetic acid (Gd-DTPA-enhanced magnetic resonance imaging of the pituitary showed hyperplasia or adenoma. Pituitary hyperplasia or adenoma with high ACTH level was considered to be the result of the insufficient therapy. The combination of hydrocortisone and bedtime dexamethasone reduced plasma ACTH levels and improved imaging findings. Since a reliable biomarker for monitoring the adequacy of replacement therapy has not yet been identified and current glucocorticoid replacement regimens do not mimic normal diurnal biorhythm of cortisol, some patients may require different glucocorticoid replacement regimens or formulas. Turk Jem 2013; 17: 15-8

  4. What Are Pituitary Tumors?

    Science.gov (United States)

    ... grow and to make steroid hormones (such as cortisol). Too much ACTH from the pituitary causes Cushing’s ... Cancer Atlas Press Room Cancer Statistics Center Volunteer Learning Center Follow Us Twitter Facebook Instagram Cancer Information, ...

  5. THE ROLE OF CORTISOL IN SKIN-DISXROMY

    OpenAIRE

    Ismailov, R.

    2009-01-01

    Cortisol is a corticosteroid hormone or glucocor ticoid produced by the adrenal gland. Cortisol can weaken the activity of the immune system. The primary control of cortisol is the primary gland, peptide, ACTH.

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

    NARCIS (Netherlands)

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

    2010-01-01

    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 repor

  7. Stages of Pituitary Tumors

    Science.gov (United States)

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... hormone that causes a woman’s breasts to make milk during and after pregnancy . Adrenocorticotropic hormone (ACTH): A ...

  8. Treatment Option Overview (Pituitary Tumors)

    Science.gov (United States)

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... hormone that causes a woman’s breasts to make milk during and after pregnancy . Adrenocorticotropic hormone (ACTH): A ...

  9. General Information about Pituitary Tumors

    Science.gov (United States)

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... hormone that causes a woman’s breasts to make milk during and after pregnancy . Adrenocorticotropic hormone (ACTH): A ...

  10. No evidence for oncogenic mutations in the adrenocorticotropin receptor gene in human adrenocortical neoplasms

    Energy Technology Data Exchange (ETDEWEB)

    Latronico, A.C.; Reincke, M.; Mendonca, B.B. [National Inst. of Child Health and Human Development, Bethesda, MD (United States)] [and others

    1995-03-01

    The mechanism(s) of tumorigenesis for the majority of adrenocortical neoplasms remain unknown. G-Protein-coupled receptors were recently proposed as candidate protooncogenes. That activating mutations of this class of receptors might be important for tumor induction or progression of endocrine neoplasms was strengthened by the recent identification of such mutations in hyperfunctioning thyroid adenomas. To examine whether the ACTH receptor (ACTH-R) gene could be an oncogene in human adrenocortical tumors, we amplified by the polymerase chain reaction and directly sequenced the entire exon of the ACTH-R gene in 25 adrenocortical tumors (17 adenomas and 8 carcinomas) and 2 adrenocortical cancer cell lines. We found no missense point mutations or even silent polymorphisms in any of the tumors and cell lines studied. We conclude that activating mutations of the ACTH-R gene do not represent a frequent mechanism of human adrenocortical tumorigenesis. 15 refs., 2 tabs.

  11. Government Ideology, Economic Pressure, and Risk Privatization. How Economic Worldviews Shape Social Policy in Times of Crisis

    DEFF Research Database (Denmark)

    Horn, Alexander

    2017-01-01

    presented with symptoms of hypercortisolism such as progressive weight gain, Cushingoid appearance, proximal myopathy, easy bruising, and amenorrhea. Blood testing including inferior petrosal sinus sampling uncovered an ACTH-producing microadenoma in the right aspect of the anterior pituitary gland...

  12. Biobehavioral Correlates of Depression in Reaction to Mental and Physical Challenge

    Science.gov (United States)

    2007-03-07

    catecholamines in response to intense exercise will diminish ( Wilmore & Costill, 2001). Acute exercise also increases ACTH and subsequently cortisol (Deuster...cortisol attenuates after an individual becomes more fit ( Wilmore & Costill, 2001). Neurohormonal response to physical challenge in depression

  13. Ontogenic development of corticotrophs in fetal buffalo (Bubalus bubalis pituitary gland

    Directory of Open Access Journals (Sweden)

    M. A. Sandhu

    2014-01-01

    Full Text Available To evaluate the subpopulation of corticotrophs in developing buffalo (Bubalus bubalis fetus, recovered pituitary glands (n=6 per group from late first, second and third gestational female buffalo dams. The corticotrophs were identified by using specific antibodies against proopiomelanocortin (POMC and adrenocorticotrophic hormone (ACTH through immunohistochemistry. There was a significant (P≤0.05 increase of immunoreactive (ir ir-ACTH cells during late 2nd trimester while, ir-POMC cells were more (P≤0.05 at late 3rd trimester of gestation as compared to other age groups. The quantity of co-localized cells for POMC and ACTH was significantly (P≤0.05 greater at the end of 1st gestation rather than 2nd and 3rd gestational fetal adenohypophyseal cells. This study is the first to demonstrate co-localization of POMC+ACTH and the affect of gestational age on the expression of these cells in buffalo fetus adenohypophysis.

  14. Serum cortisol level and adrenal reserve as a predictor of patients’ outcome after successful cardiopulmonary resuscitation

    Directory of Open Access Journals (Sweden)

    Reza Mosaddegh

    2016-06-01

    Conclusion: Current study could not show the statistically significant difference in initial and post-ACTH serum cortisol levels between survivor and non-survivor patients with cardiac arrest who had initial successful CPR, except to that of minute 60.

  15. Dexamethasone suppression test

    Science.gov (United States)

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

  16. Polyhormonal regulation of avian and mammalian corticosteroidogenesis in vitro.

    Science.gov (United States)

    Carsia, R V; Scanes, C G; Malamed, S

    1987-01-01

    1. The combined actions of ACTH, corticosterone and prolactin (PRL) in the acute regulation of corticosteroidogenesis were investigated using isolated adrenocortical cells from intact and hypophysectomized (hypox) rats (Rattus norvegicus) and from intact male domestic fowl (Gallus gallus domesticus). 2. Exogenous corticosterone suppressed to about 50% ACTH-induced corticosterone production of cells from either species. This suppression, in part, was due to corticosterone degradation. 3. oPRL, in the presence or absence of ACTH, raised corticosterone production of hypox rat cells, but not intact rat and domestic fowl cells. 4. In addition, oPRL counteracted the corticosterone-induced suppression of net ACTH-stimulated corticosterone production of hypox rat and intact domestic fowl cells, but not intact rat cells. 5. The potency of oPRL with domestic fowl cells was 4 times that with hypox rat cells. 6. Furthermore, in domestic fowl cells, the effect of oPRL was Ca2+-dependent.

  17. Tritiation of protein hormones. Progress report. [Stability of tritium-labelled protein hormones

    Energy Technology Data Exchange (ETDEWEB)

    1977-01-01

    A non-catalytic tritium exchange system using a microwave discharge technique was bult and calibrated in order to optomize the labelling of small organic molecules such as benzoic acid. Analytical and preparative chromatographic procedures, including ion exchange and molecular sieve chromatography and polyacrylamide gel electrophoresis, were standardized for use in the publication of tritium and labelled bovine ACTH. Results are reported from extensive studies of the control of chemical and biologic stability of labelled and unlabelled ACTH were carried out.

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

    Science.gov (United States)

    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.

  19. Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery

    DEFF Research Database (Denmark)

    Berg, Christian; Meinel, Timo; Lahner, Harald;

    2009-01-01

    OBJECTIVE: The glucagon stimulation test (GST) like the insulin tolerance test (ITT) stimulates both ACTH and GH secretion. However, there are limited data with modern assays on sensitivity and specificity for GST in comparison to ITT. The aim of this study was to evaluate the diagnostic utility...... alternative test for the assessment of GH reserve, but is a poor test for ACTH reserve. Test-specific cut-offs should be applied to avoid misinterpretation....

  20. Pituitary tumors containing cholecystokinin

    DEFF Research Database (Denmark)

    Rehfeld, J F; Lindholm, J; Andersen, B N

    1987-01-01

    We found small amounts of cholecystokinin in the normal human adenohypophysis and therefore examined pituitary tumors from 87 patients with acromegaly, Cushing's disease, Nelson's syndrome, prolactinoma, or inactive pituitary adenomas. Five adenomas associated with Nelson's syndrome contained......'s disease and 7 acromegaly with adenomas containing ACTH. The cholecystokinin peptides from the tumors were smaller and less sulfated than cholecystokinin from normal pituitary glands. We conclude that ACTH-producing pituitary cells may also produce an altered form of cholecystokinin....

  1. Physiological Basis for the Etiology, Diagnosis, and Treatment of Adrenal Disorders: Cushing’s Syndrome, Adrenal Insufficiency, and Congenital Adrenal Hyperplasia

    OpenAIRE

    Raff, Hershel; Sharma, Susmeeta T.; Nieman, Lynnette K.

    2014-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a classic neuroendocrine system. One of the best ways to understand the HPA axis is to appreciate its dynamics in the variety of diseases and syndromes that affect it. Excess glucocorticoid activity can be due to endogenous cortisol overproduction (spontaneous Cushing’s syndrome) or exogenous glucocorticoid therapy (iatrogenic Cushing’s syndrome). Endogenous Cushing’s syndrome can be subdivided into ACTH-dependent and ACTH-independent, the latt...

  2. Relation of addiction genes to hypothalamic gene changes subserving genesis and gratification of a classic instinct, sodium appetite

    OpenAIRE

    Liedtke, Wolfgang B.; McKinley, Michael J; Walker, Lesley L.; Zhang, Hao; Pfenning, Andreas R.; Drago, John; Hochendoner, Sarah J.; Hilton, Donald L.; Lawrence, Andrew J.; Denton, Derek A.

    2011-01-01

    Sodium appetite is an instinct that involves avid specific intention. It is elicited by sodium deficiency, stress-evoked adrenocorticotropic hormone (ACTH), and reproduction. Genome-wide microarrays in sodium-deficient mice or after ACTH infusion showed up-regulation of hypothalamic genes, including dopamine- and cAMP-regulated neuronal phosphoprotein 32 kDa (DARPP-32), dopamine receptors-1 and -2, α-2C- adrenoceptor, and striatally enriched protein tyrosine phosphatase (STEP). Both DARPP-32 ...

  3. Glucocorticoid control of steroidogenesis in isolated rat adrenocortical cells.

    Science.gov (United States)

    Carsia, R V; Malamed, S

    1983-08-17

    The role of end-product glucocorticoids in the regulation of corticosteroidogenesis in isolated adrenocortical cells was investigated. Trypsin-isolated cells from male rat adrenal glands were incubated with or without corticotropin (ACTH) and with or without corticosterone. Endogenous corticosterone production was determined by radioimmunoassay at the end of incubation. Cessation of ACTH-induced corticosterone production was apparent after 2-4 h of incubation. The suppression occurred later with lower cell concentrations. Corticosterone production was partially restored after washing the suppressed cells. Supernatant fluid from suppressed cell suspensions also suppressed steroidogenesis of a fresh population of cells. However, the suppressing property of the supernatant fluid was abolished after the removal of corticosterone by charcoal-dextran treatment, suggesting that corticosterone or other steroids caused the suppression. Exogenous corticosterone induced suppression over a wide range of ACTH concentrations, but did not change the half-maximal steroidogenic concentration of ACTH, indicating that the suppression does not change the sensitivity of the cells to ACTH. Suppression occurred within 30-60 min after corticosterone had been added to the incubation medium either at the start of incubation or while steroidogenesis was in progress. Suppression varied directly with the concentration of exogenous corticosterone. These data indicate that glucocorticoids can directly and acutely suppress corticosteroidogenesis and thus control adrenocortical function in concert with other regulators such as ACTH and Ca2+.

  4. Basal and Adrenocorticotropic Hormone Stimulated Plasma Cortisol Levels Among Egyptian Autistic Children: Relation to Disease Severity

    Directory of Open Access Journals (Sweden)

    Hewedi Doaa H

    2010-10-01

    Full Text Available Abstract Background Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism. Aim To assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH levels in autistic children and their relationship to disease characteristics. Methods Fifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated and ACTH. In addition, electroencephalography (EEG and intelligence quotient (IQ assessment were done for all autistic children. Results Sixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032 and stimulated cortisol (p = 0.04 and higher ACTH (p = 0.01 than controls. Childhood Autism Rating Scale (CARS score correlated positively with ACTH (r = 0.71, p = 0.02 and negatively with each of basal (r = -0.64, p = 0.04 and stimulated cortisol (r = -0.88, p Conclusions The observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism.

  5. A Challenging Case of an Ectopic Cushing Syndrome

    Directory of Open Access Journals (Sweden)

    Joana Menezes Nunes

    2014-01-01

    Full Text Available Bronchopulmonary carcinoids are rare pulmonary neoplasms although they account for most cases of ectopic ACTH syndromes. When feasible, the mainstay treatment is surgical resection of the tumor. We report the case of a 52-year-old woman with signs and symptoms suggestive of hypercortisolism for 12 months, admitted to our department because of community acquired pneumonia. Blood hormone analysis showed increased levels of ACTH and urinary free cortisol and nonsuppressibility to high- and low-dose dexamethasone tests. Pituitary MRI showed no lesion and no central-to-peripheral ACTH gradient was present in bilateral inferior petrosal sinus sampling. CRH stimulation test suggested an ectopic ACTH source. Thoracic CT scan revealed a nodular region measuring 12 mm located in the inferior lingular lobule of the left superior lung with negative uptake by 18-FDG-PET scan and negative SRS. The patient was successfully treated with an atypical lung resection and histology revealed an atypical bronchial carcinoid tumor with positive ACTH immunoreactivity. This was an interesting case because the patient was admitted due to pneumonia that may have been associated with her untreated and chronic hypercortisolism and a challenging case of ectopic ACTH syndrome due to conflicting results on the diagnostic exams.

  6. Differential gene expression by fiber-optic beadarray and pathway in adrenocorticotrophin-secreting pituitary adenomas

    Institute of Scientific and Technical Information of China (English)

    JIANG Zhi-quan; GUI Song-bo; ZHANG Ya-zhuo

    2010-01-01

    Background Adrenocorticotrophin (ACTH)-secreting pituitary adenomas account for approximately 7%-14% of all pituitary adenomas, but its pathogenesis is still enigmatic. This study aimed to explore mechanisms underlying the pathogenesis of ACTH-secreting pituitary adenomas.Methods We used fiber-optic beadarray to examine gene expression in three ACTH-secreting adenomas compared with three normal pituitaries. Four differentially expressed genes from the three ACTH-secreting adenomas and three normal pituitaries were chosen randomly for validation by reverse transcriptase-real time quantitative polymerase chain reaction (RT-qPCR). We then analyzed the differentially expressed gene profile with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway.Results Fiber-optic beadarray analysis showed that the expression of 28 genes and 8 expressed sequence tags (ESTs)were significantly increased and the expression of 412 genes and 31 ESTs were significantly decreased. Bioinformatic and pathway analysis showed that the genes HIGD1B, EPS8, HPGD, DAPK2, and IGFBP3 and the transforming growth factor (TGF)-β signaling pathway and extracellular matrix (ECM)-receptor interaction pathway may play important roles in tumorigenesis and progression of ACTH-secreting pituitary adenomas.Conclusions Our data suggest that numerous aberrantly expressed genes and several pathways are involved in the pathogenesis of ACTH-secreting pituitary adenomas. Fiber-optic beadarray combined with pathway analysis of differential gene expression appears to be a valid method of investigating tumour pathogenesis.

  7. Some dipeptides reverse the inhibitory effect of GABA on /sup 35/S-TBPS binding

    Energy Technology Data Exchange (ETDEWEB)

    Squires, R.F.; Saederup, E.

    1987-05-01

    All known GABA-A receptor blocker reverse the inhibitory effect of GABA on /sup 35/S-t-butylphosphorothionate (TBPS) binding to rat brain membranes in vitro. This system has already been used to identify several novel GABA antagonists. The authors now report that 12 out of 52 dipeptides tested (all containing L-amino acids), at 1 mM, significantly reverse the inhibitory effect of 1 ..mu..M GABA, which inhibits specific /sup 35/S-TBPS binding about 60%. Most of the active dipeptides contain an aromatic and a basic amino acid. Tryptophan usually conferred greater activity than phe or tyr, while arg usually conferred greater activity than lys or his. Several larger peptides containing the HFRW sequence found in ACTH were also GABA antagonists; ACTH(1-24), ACTH(1-18), ACTH(1-13), ACTH(4-10) and ..gamma..-MSH while ACTH(11-24) was inactive. The excitatory effects of these later peptides may be in part due to blockade of GABA-A receptors.

  8. Type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog.

    Directory of Open Access Journals (Sweden)

    L Insabato

    2010-11-01

    Full Text Available The Silent Corticotroph Adenoma (SCA is a pituitary adenoma variant characterized by the immunoreactivity for adrenocorticotropic hormone (ACTH and related peptides, without the clinical signs of Cushing's disease. SCA has been postulated to either secrete structurally abnormal ACTH that is inactive but detectable by immunohistochemistry or radioimmunoassay, or to secrete ACTH intermittently or at low levels continuously. Excess of ACTH has been associated to type II muscle atrophy. We describe a case of type II muscle fibers atrophy associated with silent corticotroph adenoma in a dog. The dog showed moderate to severe proximal muscle wasting and weakness with normal levels of muscle-associated enzymes. In the limb muscle biopsies, type II fibers were uniformly smaller than type I fibers. In temporalis muscles, there were few atrophic fibers, and several irregular areas of loss of enzymatic activity observed in NADH, SDH and COX stains. The tumour showed a trabecular growth pattern and immunohistochemical analysis demonstrated the presence of cytoplasmic immunoreactivity for ACTH. The muscle atrophy was considered to be related to an excess of inactive ACTH. Studying spontaneous occurring rare diseases in animals could help to understand the mechanism of similar diseases in human has well.

  9. Assessment of adrenocortical activity by non-invasive measurement of faecal cortisol metabolites in dromedary camels (Camelus dromedarius).

    Science.gov (United States)

    Sid-Ahmed, Omer-Elfaroug; Sanhouri, Ahmed; Elwaseela, Badr-Eldin; Fadllalah, Imad; Mohammed, Galal-Eldin Elazhari; Möstl, Erich

    2013-08-01

    The aim of this study was to determine whether glucocorticoid production could be monitored non-invasively in dromedary camels by measuring faecal cortisol metabolites (FCMs). Five Sudanese dromedaries, two males and three females, were injected with a synthetic adrenocorticotropic hormone (ACTH) analogue. Blood samples were collected pre- and post-ACTH injection. Faeces were sampled after spontaneous defecation for five consecutive days (2 days before and 3 days after ACTH injection). Baseline plasma cortisol values ranged from 0.6 to 10.8 ng/ml in males and from 1.1 to 16.6 ng/ml in females, while peak values after ACTH injection were 10.9-41.9 in males and 10-42.2 ng/ml in females. Peak blood cortisol values were reached between 1.5 and 2.0 h after ACTH injection. The concentration of FCMs increased after ACTH injection in the faeces of both sexes, although steroid levels peaked earlier in males [24 h; (286.7-2,559.7 ng/g faeces)] than in females [36-48 h; (1,182.6-5,169.1 ng/g faeces)], reflecting increases of 3.1-8.3- and 4.3-8-fold above baseline levels. To detect chromatographic patterns of immunoreactive FCMs, faecal samples with high FCM concentrations from both sexes were pooled and subjected to reverse phase high performance liquid chromatography (RP-HPLC). RP-HPLC analysis revealed sex differences in the polarity of FCMs, with females showing more polar FCMs than males. We concluded that stimulation of adrenocortical activity by ACTH injection resulted in a measurable increase in blood cortisol that was reliably paralleled by increases in FCM levels. Thus, measurement of FCMs is a powerful tool for monitoring the adrenocortical responses of dromedaries to stressors in field conditions.

  10. Gene array and real time PCR analysis of the adrenal sensitivity to adrenocorticotropic hormone in pig

    Directory of Open Access Journals (Sweden)

    SanCristobal Magali

    2008-02-01

    Full Text Available Abstract Background Variability in hypothalamic-pituitary-adrenal (HPA axis activity has been shown to be influenced by genetic factors and related to great metabolic differences such as obesity. The aim of this study was to investigate molecular bases of genetic variability of the adrenal sensitivity to ACTH, a major source of variability, in Meishan (MS and Large White (LW pigs, MS being reported to exhibit higher basal cortisol levels, response to ACTH and fatness than LW. A pig cDNA microarray was used to identify changes in gene expression in basal conditions and in response to ACTH stimulation. Results Genotype and/or ACTH affected the expression of 211 genes related to transcription, cell growth/maintenance, signal transduction, cell structure/adhesion/extra cellular matrix and protein kinase/phosphatase activity. No change in the expression of known key regulator proteins of the ACTH signaling pathway or of steroidogenic enzymes was found. However, Mdh2, Sdha, Suclg2, genes involved in the tricarboxylic acid (TCA pathway, were over-expressed in MS pigs. Higher TCA cycle activity in MS than in LW may thus result in higher steroidogenic activity and thus explain the typically higher cortisol levels in MS compared to LW. Moreover, up-regulation of Star and Ldlr genes in MS and/or in response to ACTH suggest that differences in the adrenal function between MS and LW may also involve mechanisms requisite for cholesterol supply to steroidogenesis. Conclusion The present study provides new potential candidate genes to explain genetic variations in the adrenal sensitivity to ACTH and better understand relationship between HPA axis activity and obesity.

  11. The Effect of Alpha-Lipoic Acid on Mitochondrial Superoxide and Glucocorticoid-Induced Hypertension

    Directory of Open Access Journals (Sweden)

    Sharon L. H. Ong

    2013-01-01

    Full Text Available Aims. To examine the effect of alpha-lipoic acid, an antioxidant with mitochondrial superoxide inhibitory properties, on adrenocorticotrophic hormone- (ACTH-HT and dexamethasone-induced hypertensions (DEX-HT in rats and if any antihypertensive effect is mediated via mitochondrial superoxide inhibition. Methods. In a prevention study, rats received ground food or alpha-lipoic-acid-laced food (10 mg/rat/day for 15 nights. Saline, adrenocorticotrophic hormone (ACTH, 0.2 mg/kg/day, or dexamethasone (DEX, 10 μg/rat/day was injected subcutaneously from day 5 to day 11. In a reversal study, rats received alpha-lipoic-acid-laced food 4 days after commencement of saline or DEX. Tail-cuff systolic blood pressure (SBP was measured second daily. Kidney mitochondrial superoxide was examined using (MitoSOX Red (MitoSOX via flow cytometry. Results. SBP was increased by ACTH (P<0.0005 and DEX (P<0.0005. Alpha-lipoic acid alone did not alter SBP. With alpha-lipoic acid pretreatment, SBP was increased by ACTH (P′<0.005 but not by DEX. Alpha-lipoic partially prevented ACTH-HT (P′<0.0005 and fully prevented DEX-HT (P′<0.0005 but failed to reverse DEX-HT. ACTH and DEX did not increase MitoSOX signal. In ACTH-hypertensive rats, high-dose alpha-lipoic acid (100 mg/rat/day did not decrease SBP further but raised MitoSOX signal (P<0.001, suggesting prooxidant activity. Conclusion. Glucocorticoid-induced hypertension in rats is prevented by alpha-lipoic acid via mechanisms other than mitochondrial superoxide reduction.

  12. Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism

    Institute of Scientific and Technical Information of China (English)

    Wen-Bo Wang; Fei She; Li-Fang Xie; Wen-Hua Yan; Jin-Zhi Ouyang; Bao-An Wang; Hang-Yun Ma

    2016-01-01

    Background:Prolonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism (IHH) may produce adverse effects on the endocrine homeostasis and metabolism.This study aimed to compare basal serum adrenocorticotropic hormone (ACTH) and cortisol levels between male IHH patients and healthy controls.Moreover,this study compared the basal hypothalamic-pituitary-adrenal (HPA) axis in patients with and without nonalcoholic fatty liver disease (NAFLD),and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients.Methods:This was a retrospective case-control study involving 75 Chinese male IHH patients (mean age 21.4 ± 3.8 years,range 17-30 years) and 135 healthy controls after matching for gender and age.All subjects underwent physical examination and blood testing for serum testosterone,luteinizing hormone,follicle-stimulating hormone,ACTH,and cortisol and biochemical tests.Results:Higher basal serum ACTH levels (8.25 ± 3.78 pmol/L vs.6.97 ± 2.81 pmol/L) and lower cortisol levels (366.70 ± 142.48 nmol/L vs.452.82 ± 141.53 nmol/L) were observed in male IHH patients than healthy subjects (all P < 0.05).IHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD (34.9% vs.4.4%) than the controls (all P < 0.05).Basal serum ACTH (9.91 ± 4.98 pmol/L vs.7.60 ± 2.96 pmol/L) and dehydroepiandrosterone sulfate (2123.7 ± 925.8 μg/L vs.1417.1 ± 498.4 μg/L) levels were significantly higher in IHH patients with NAFLD than those without NAFLD (all P < 0.05).We also found that basal serum ACTH levels were positively correlated with NAFLD (r =0.289,P < 0.05) and triglyceride levels (r =0.268,P < 0.05) in male IHH patients.Furthermore,NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis.Conclusions:The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls.NAFLD was

  13. Impaired adrenergic- and corticotropic-axis outflow during exercise in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Iranmanesh, Ali; Rochester, Dudley F; Liu, Jing; Veldhuis, Johannes D

    2011-11-01

    Exercise stimulates coordinated release of the sympathoadrenal hormones adrenocorticotropic hormone (ACTH), cortisol, norepinephrine (NE), and epinephrine (Epi). The study hypothesis was that chronic obstructive pulmonary disease (COPD) is marked by heightened sympathoadrenal outflow at comparable relative workloads. The location of the study was at a clinical research unit. Eight healthy men and 9 men with stable COPD (forced expiratory volume at 1 second exercised at individual submaximal (35% ± 5%) or maximal oxygen consumption. Blood was sampled every 2 minutes for 40 minutes concurrently. Two-way analysis of covariance was applied to examine group (healthy/COPD) and exercise (3 levels) effects on ACTH, cortisol, NE, and Epi release and regularity (estimable by approximate entropy). The timing of peak hormone concentrations was Epi, 14 minutes; NE, 16 minutes; ACTH, 22 minutes; and cortisol, 34 minutes in both cohorts. Type of exercise regimen influenced all 4 hormones (each P COPD) affected cortisol (P Exercise regimen and group together controlled ACTH, cortisol, and Epi (each P COPD compared with control subjects. Approximate entropy analysis also identified loss of maximal exercise-induced ACTH-secretory regularity in COPD patients (P = .042). These outcomes demonstrate impaired rather than augmented exercise-associated sympathocorticotropic-axis outflow in patients with COPD even when outcomes are normalized to maximal oxygen consumption, suggesting that factors other than fitness are at work.

  14. Glucagon-like peptide-2-induced memory improvement and anxiolytic effects in mice.

    Science.gov (United States)

    Iwai, Takashi; Jin, Kazushi; Ohnuki, Tomoko; Sasaki-Hamada, Sachie; Nakamura, Minami; Saitoh, Akiyoshi; Sugiyama, Azusa; Ikeda, Masaatsu; Tanabe, Mitsuo; Oka, Jun-Ichiro

    2015-02-01

    We investigated the effectiveness of glucagon-like peptide-2 (GLP-2) on memory impairment in lipopolysaccharide (LPS)-treated mice, and anxiety-like behavior in adrenocorticotropic hormone (ACTH)-treated mice. In the Y-maze test, LPS (10 µg/mouse, i.c.v.) significantly decreased spontaneous alternation, which was prevented by pretreatment with GLP-2 (0.01-0.3 µg/mouse, i.c.v.). The GLP-2 treatment just before the Y-maze test also improved LPS-induced memory impairment. Continuous treatment with GLP-2 (3 µg/mouse, i.c.v.) had no effect on the open-field test in saline-treated or ACTH-treated mice. Chronic ACTH treatment did not cause anxiogenic effects in the elevated plus-maze test. GLP-2 showed weak anxiolytic-like effects in the elevated plus-maze test in ACTH-treated, but not saline-treated mice. Moreover, GLP-2 increased 5-HT, but not 5-HIAA and tryptophan hydroxylase 2 levels in the amygdala of ACTH-treated mice. Pharmacological depletion of 5-HT prevented the anxiolytic effects of GLP-2. These results suggest that GLP-2 protected and improved memory function in LPS-treated mice, and also had anxiolytic effects due to changes in the 5-HT system.

  15. Steroid control of steroidogenesis in isolated adrenocortical cells: molecular and species specificity.

    Science.gov (United States)

    Carsia, R V; Macdonald, G J; Malamed, S

    1983-06-01

    The molecular and species specificity of glucocorticoid suppression of corticosteroidogenesis was investigated in isolated adrenocortical cells. Trypsin-isolated cells from male rat, domestic fowl and bovine adrenal glands were incubated with or without steroidogenic agents and with or without steroids. Glucocorticoids were measured by radioimmunoassay or fluorometric assay after 1-2 h incubation. Glucocorticoids suppressed ACTH-induced steroidogenesis of isolated rat cells with the following relative potencies: corticosterone greater than cortisol = cortisone greater than dexamethasone. The mineralocorticoid, aldosterone did not affect steroidogenesis. Suppression by glucocorticoids was acute (within 1-2 h), and varied directly with the glucocorticoid concentration. Testosterone also suppressed ACTH-induced steroidogenesis. Glucocorticoid-type steroids have equivalent suppressive potencies, thus suggesting that these steroids may induce suppression at least partly by a common mechanism. Although corticosterone caused the greatest suppression, testosterone was more potent. The steroid specificity of suppression of cyclic AMP (cAMP)-induced and ACTH-induced steroidogenesis were similar, suggesting that suppression is not solely the result of interference with ACTH receptor function or the induction of adenylate cyclase activity. Exogenous glucocorticoids also suppressed ACTH-induced steroidogenesis of cells isolated from domestic fowl and beef adrenal glands, thus suggesting that this observed suppression may be a general mechanism of adrenocortical cell autoregulation.

  16. Hypothalamus-pituitary-adrenal axis suppression following induction chemotherapy in children with acute lymphoblastic leukemia

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    Perdomo-Ramírez, Iván

    2016-01-01

    Full Text Available Background: Adrenal insufficiency has been reported in 46 % to 81.5 % of children receiving corticosteroids for acute lymphoblastic leukemia (ALL. Methodology: To assess the frequency of such insufficiency, 40 patients under 18 years (mean: 8.5 years with new diagnosis of ALL were studied. Base-line cortisol and adrenocorticotropin (ACTH levels were measured, and they received 5-week therapy with prednisolone. After 3 days off-steroid therapy, a stimulation test with ACTH 1 μg was done. In patients with abnormal cortisol (<18 μg/dL new ACTH tests were done and cortisol levels were determined at days 7, 14 and 30 until cortisol post-stimulation levels were normal. Results: Three days after the last steroid dose 29/40 (72.5 % had adrenal insufficiency after ACTH stimulus. At day 30 no one had abnormal cortisol levels after ACTH stimulus. All patients with adrenal suppression were over 5 years (HR 4.69; CI95 %: 1.44-15.32; p = 0.011. Conclusion: Steroids used during ALL treatment may cause adrenal insufficiency. Patients over 5 years are at high risk of developing adrenal suppression. We suggest to follow-up those patients with stress episodes after induction chemotherapy as steroid supplementation may be indicated.

  17. New insights into the controversy of adrenal function during critical illness.

    Science.gov (United States)

    Boonen, Eva; Bornstein, Stefan R; Van den Berghe, Greet

    2015-10-01

    Critical illness represents a life-threatening disorder necessitating recruitment of defence mechanisms for survival. Herein, the hypothalamic-pituitary-adrenal axis is essential. However, the relevance of a relative insufficiency of the hypothalamic-pituitary-adrenal axis in critical illness, which is diagnosed by a suppressed cortisol response to exogenous adrenocorticotropic hormone (ACTH) irrespective of the plasma cortisol concentration, is controversial. Findings from several studies have provided insights that clarify at least part of this controversy. Rather than an activated hypothalamic-pituitary-adrenal axis, ACTH-independent regulators have been reported to contribute to increased cortisol availability during critical illness. One of these regulators is reduced cortisol breakdown, mediated by suppressed expression and activity of cortisol metabolising enzymes in the liver and kidneys. This downstream mechanism increases concentrations of plasma cortisol, but the ensuing feedback-inhibited ACTH release, when sustained for more than 1 week, has been shown to negatively affect adrenocortical integrity and function. Reduced adrenocortical ACTH signalling could explain reduced cortisol responses to exogenous ACTH. Whether such reduced cortisol responses in the presence of raised plasma (free) cortisol identifies adrenal failure needing treatment is unlikely. Additionally, reduced cortisol breakdown affects the optimum dose of hydrocortisone treatment during critical illness. Identification of patients with an insufficient hypothalamic-pituitary-adrenal axis response and the optimum treatment for this disorder clearly need more well designed preclinical and clinical studies.

  18. Forced desynchrony reveals independent contributions of suprachiasmatic oscillators to the daily plasma corticosterone rhythm in male rats.

    Science.gov (United States)

    Wotus, Cheryl; Lilley, Travis R; Neal, Adam S; Suleiman, Nicole L; Schmuck, Stefanie C; Smarr, Benjamin L; Fischer, Brian J; de la Iglesia, Horacio O

    2013-01-01

    The suprachiasmatic nucleus (SCN) is required for the daily rhythm of plasma glucocorticoids; however, the independent contributions from oscillators within the different subregions of the SCN to the glucocorticoid rhythm remain unclear. Here, we use genetically and neurologically intact, forced desynchronized rats to test the hypothesis that the daily rhythm of the glucocorticoid, corticosterone, is regulated by both light responsive and light-dissociated circadian oscillators in the ventrolateral (vl-) and dorsomedial (dm-) SCN, respectively. We show that when the vlSCN and dmSCN are in maximum phase misalignment, the peak of the plasma corticosterone rhythm is shifted and the amplitude reduced; whereas, the peak of the plasma adrenocorticotropic hormone (ACTH) rhythm is also reduced, the phase is dissociated from that of the corticosterone rhythm. These data support previous studies suggesting an ACTH-independent pathway contributes to the corticosterone rhythm. To determine if either SCN subregion independently regulates corticosterone through the sympathetic nervous system, we compared unilateral adrenalectomized, desynchronized rats that had undergone either transection of the thoracic splanchnic nerve or sham transection to the remaining adrenal. Splanchnicectomy reduced and phase advanced the peak of both the corticosterone and ACTH rhythms. These data suggest that both the vlSCN and dmSCN contribute to the corticosterone rhythm by both reducing plasma ACTH and differentially regulating plasma corticosterone through an ACTH- and sympathetic nervous system-independent pathway.

  19. Regulation of corticosterone production by vasopressin during water restriction and after drinking in rats.

    Science.gov (United States)

    Wotus, Cheryl; Osborn, John W; Nieto, Pilar Ariza; Engeland, William C

    2003-12-01

    Plasma vasopressin (VP) and corticosterone have each been shown to be rapidly suppressed after drinking in different models of osmotic stimulation in rats; however, no causal relationship between these responses has been investigated. Studies were performed to determine if plasma VP and corticosterone are reduced in parallel after drinking and if manipulation of plasma VP affects plasma, ACTH corticotropins and corticosterone in a model of water restriction. A strong correlation between changes in plasma VP and corticosterone, but not between plasma ACTH and corticosterone, was observed after drinking induced by 6 days of water restriction. Similarly, ingestion of isotonic saline resulted in a biphasic VP response that was paralleled by adrenal and plasma corticosterone, but not by plasma ACTH. Administration of an immunoneutralizing antibody directed against VP resulted in a rapid decrease in plasma corticosterone, but not ACTH, in water-restricted rats, but not in rats receiving water ad libitum. These data suggest that during dehydration, elevated plasma VP can stimulate the production of corticosterone by the adrenal, independently of ACTH. Moreover, they support the hypothesis that the decline in corticosterone after restriction-induced drinking is due, in part, to a decline in plasma VP.

  20. Forced desynchrony reveals independent contributions of suprachiasmatic oscillators to the daily plasma corticosterone rhythm in male rats.

    Directory of Open Access Journals (Sweden)

    Cheryl Wotus

    Full Text Available The suprachiasmatic nucleus (SCN is required for the daily rhythm of plasma glucocorticoids; however, the independent contributions from oscillators within the different subregions of the SCN to the glucocorticoid rhythm remain unclear. Here, we use genetically and neurologically intact, forced desynchronized rats to test the hypothesis that the daily rhythm of the glucocorticoid, corticosterone, is regulated by both light responsive and light-dissociated circadian oscillators in the ventrolateral (vl- and dorsomedial (dm- SCN, respectively. We show that when the vlSCN and dmSCN are in maximum phase misalignment, the peak of the plasma corticosterone rhythm is shifted and the amplitude reduced; whereas, the peak of the plasma adrenocorticotropic hormone (ACTH rhythm is also reduced, the phase is dissociated from that of the corticosterone rhythm. These data support previous studies suggesting an ACTH-independent pathway contributes to the corticosterone rhythm. To determine if either SCN subregion independently regulates corticosterone through the sympathetic nervous system, we compared unilateral adrenalectomized, desynchronized rats that had undergone either transection of the thoracic splanchnic nerve or sham transection to the remaining adrenal. Splanchnicectomy reduced and phase advanced the peak of both the corticosterone and ACTH rhythms. These data suggest that both the vlSCN and dmSCN contribute to the corticosterone rhythm by both reducing plasma ACTH and differentially regulating plasma corticosterone through an ACTH- and sympathetic nervous system-independent pathway.

  1. Linking disease symptoms and subtypes with personalized systems-based phenotypes: a proof of concept study.

    Science.gov (United States)

    Aschbacher, Kirstin; Adam, Emma K; Crofford, Leslie J; Kemeny, Margaret E; Demitrack, Mark A; Ben-Zvi, Amos

    2012-10-01

    A dynamic systems model was used to generate parameters describing a phenotype of Hypothalamic-Pituitary-Adrenal (HPA) behavior in a sample of 36 patients with chronic fatigue syndrome (CFS) and/or fibromyalgia (FM) and 36 case-matched healthy controls. Altered neuroendocrine function, particularly in relation to somatic symptoms and poor sleep quality, may contribute to the pathophysiology of these disorders. Blood plasma was assayed for cortisol and ACTH every 10 min for 24h. The dynamic model was specified with an ordinary differential equation using three parameters: (1) ACTH-adrenal signaling, (2) inhibitory feedback, and (3) non-ACTH influences. The model was "personalized" by estimating an individualized set of parameters from each participant's data. Day and nighttime parameters were assessed separately. Two nocturnal parameters (ACTH-adrenal signaling and inhibitory feedback) significantly differentiated the two patient subgroups ("fatigue-predominant" patients with CFS only versus "pain-predominant" patients with FM and comorbid chronic fatigue) from controls (all p'sdecreased when more cortisol was produced per unit ACTH, is consistent with cortisol's anti-inflammatory and sleep-modulatory effects. Patients' HPA systems may compensate by promoting more rapid or sustained cortisol production. Mapping "behavioral phenotypes" of stress-arousal systems onto symptom clusters may help disentangle the pathophysiology of complex disorders with frequent comorbidity.

  2. Ectopic corticotroph syndrome

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    Penezić Zorana

    2004-01-01

    Full Text Available INTRODUCTION Endogenous Cushing's syndrome is a clinical state resulting from prolonged, inappropriate exposure to excessive endogenous secretion of Cortisol and hence excess circulating free cortisol, characterized by loss of the normal feedback mechanisms of the hypothalamo-pituitary-adrenal axis and the normal circadian rhythm of cortisol secretion [2]. The etiology of Cushing's syndrome may be excessive ACTH secretion from the pituitary gland, ectopic ACTH secretion by nonpituitary tumor, or excessive autonomous secretion of cortisol from a hyperfunctioning adrenal adenoma or carcinoma. Other than this broad ACTH-dependent and ACTH-independent categories, the syndrome may be caused by ectopic CRH secretion, PPNAD, MAH, ectopic action of GIP or catecholamines, and other adrenel-dependent processes associated with adrenocortical hyperfunction. CASE REPORT A 31 year-old men with b-month history of hyperpigmentation, weight gain and proximal myopathy was refereed to Institute of Endocrinology for evaluation of hypercortisolism. At admission, patient had classic cushingoid habit with plethoric face, dermal and muscle atrophy, abdominal strie rubrae and centripetal obesity. The standard laboratory data showed hyperglycaemia and hypokaliemia with high potassium excretion level. The circadian rhythm of cortisol secretion was blunted, with moderately elevated ACTH level, and without cortisol suppression after low-dose and high-dose dexamethason suppression test. Urinary 5HIAA was elevated. Abdominal and sellar region magnetic resonance imaging was negative. CRH stimulation resulted in ACTH increase of 87% of basal, but without significant increase of cortisol level, only 7%. Thoracal CT scan revealed 14 mm mass in right apical pulmonary segment. A wedge resection of anterior segment of right upper lobe was performed. Microscopic evaluation showed tumor tissue consisting of solid areas of uniform, oval cells with eosinophilic cytoplasm and centrally

  3. Hipofunción glucocorticoide en la distrofia miotónica Glucocorticoid hypofunction in myotonic dystrophy

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    L. Forga

    2007-08-01

    Full Text Available Introducción. La distrofia miotónica (DM1 es una enfermedad autonómica dominante cuyo defecto genético consiste en una expansión por repeticiones del triplete CTG en un gen que codifica una proteín-kinasa serina-treonina AMPc dependiente llamada DMPK. Se trata de una enfermedad multisistémica con conocida repercusión endocrinológica. En cuanto a la función suprarrenal, los resultados descritos han sido variables aunque últimamente se interpretan como indicadores de una hiperactividad del eje hipotálamo-hipófiso-adrenal. Material y métodos. Se han estudiado 25 pacientes (13 hombres y 12 mujeres afectos de DM1 a los que se ha analizado: cortisol y ACTH basales, test de estímulo con 0,25 mg de ACTH para cortisol y test de CRH para cortisol y ACTH. Asimismo se valoró el grado de expansión de CTG por Southern blot y PCR. Como grupo control para basales se estudiaron 25 individuos sanos equiparables por edad y sexo, a 11 de los cuales se realizó test de CRH. Resultado. Se diagnosticó a un paciente de insuficiencia suprarrenal primaria no autoinmune. En el resto de casos no hubo diferencias entre la ACTH basal de pacientes y controles, y la respuesta de cortisol a ACTH fue normal. Los pacientes presentaron un nivel de cortisol basal más bajo (pIntroduction. Myotonic dystrophy (DM1 is an autosomal dominant disorder whose genetic defect consists of the amplification of an unstable CTG trinucleotide repeat in the 3’ untranslated region of the dystrophia myotonica protein kinase gene (DMPK. This is a multi-systemic disease with a well-known endocrinological repercussion. With respect to the adrenal function variable results have been described, although lately they are interpreted as indicators of a hyperactivity of the hypothalamic-pituitary-adrenal (HPA axis Material and methods. Twenty-five patients (13 men and 12 women with DM1 were recruited. They were analysed for: basal cortisol and ACTH, stimulus test with 0.25 mg of ACTH for

  4. Immunocytochemical demonstration of proopiomelanocortin- and other opioid-related substances and a CRF-like peptide in the gut of the american cockroach, Periplaneta americana L.

    Science.gov (United States)

    Schols, D; Verhaert, P; Huybrechts, R; Vaudry, H; Jégou, S; De Loof, A

    1987-01-01

    Using the peroxidase-antiperoxidase technique, we showed the presence of peptides which are immunologically resembling mammalian corticotropin releasing hormone (CRF)-, adrenocorticotropic hormone (ACTH)-, beta-endorphin (beta-END)-, alpha-melanocyte stimulating hormone (alpha-MSH)-, methionine-enkephalin (met-ENK)- and leucine enkephalin (leu-ENK)- like immunoreactivity in hundreds to thousands of endocrine cells and nerve fibers in the midgut of the American cockroach Periplaneta americana. In the cockroach hindgut no immunoreactive cell bodies could be observed, although nerve fibers were clearly noticed to be recognized by antisera to CRF, ACTH1-24, ACTH11-24 and beta-END. Nothing is exactly known as to the function(s) of the demonstrated materials, but one can speculate that these numerous immunoreactive cells, might have important paracrine and/or endocrine functions in the insect physiology.

  5. Pituitary hormone responses to meta-chlorophenylpiperazine in panic disorder and healthy control subjects.

    Science.gov (United States)

    Kahn, R S; Wetzler, S; Asnis, G M; Kling, M A; Suckow, R F; van Praag, H M

    1991-04-01

    The present study reports adrenocorticotropic hormone (ACTH) and prolactin responses after oral administration of 0.25 mg/kg of the serotonin agonist, meta-chlorophenylpiperazine (MCPP), in patients with panic disorder (PD) and in healthy subjects. MCPP blood levels were similar for the two groups, but almost twice as high in males as in females. Female patients had augmented ACTH and prolactin release as compared to healthy females, while ACTH and prolactin release in male patients was similar to that of male controls. These results suggest that female PD patients have hypersensitive serotonin receptors. Moreover, they indicate that pharmacokinetic gender differences may affect challenge studies, and that different doses may be required to study neuroendocrine responses in males and females.

  6. Plasma cortisol activity in rats under conditions of chronic stress supplemented with resveratrol

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    Miryam Vélez-Marín

    2012-09-01

    Full Text Available Normal 0 21 false false false ES-CO X-NONE X-NONE Objective: Determine the activity of cortisol in rats treated with exogenous ACTH and a resveratrol supplement. Methodology; Forty-eight adult male rats and 16 adult female rats (Rattus norvegicus three months old with a body weight of 200 to 250g and 300 to 350g for both male and female were used and kept in controlled environmental conditions, temperature of 20±2°C and light-dark cycles of 14 and 10 hours. They were fed with balanced food and had free access to water. The rats were randomly divided into four groups: group 1, was treated with 5 µg/kg of ACTH i.p. every twelve hours; group 2, received the same treatment with ACTH plus a grape extract supplementation of 40 mg/Kg; group 3, only received grape extract and group 4, served as control and only received saline solution (0,9% i.p. The experimental was designed as a 2×2 factorial with two ACTH levels and two extract grape levels. Results:  Significant differences were not found in cortisol concentrations for day, gender or treatment effects (0.75ug/dl ± 0.11; p Conclusion: Results suggest that chronic stress and consume of resveratrol did not produce any effect in the activity of plasmatic cortisol, in stressed and unstressed rats stressed. In the same way, possibly, dose of ACTH did not produce stimulation of the suprarenal gland for these animals. Key words: ACTH, adrenal, cortisol, stress, rat wistar, resveratrol.RESUMEN Objetivo: Determinar la actividad de cortisol en ratas tratadas con ACTH exógena y un suplemento de resveratrol. Metodología: Se utilizaron 48 ratas hembras adultas y 16 machos de la cepa wistar (Rattus norvegicus de tres meses de edad y con un peso corporal de 200-250g y 300-350, para hembras y machos, respectivamente, los cuales permanecieron bajo condiciones ambientales controladas, temperatura 20±2°C de ciclos de luz-oscuridad de 14 y 10 horas, respectivamente. Se les proporcionó alimento balanceado con

  7. Factors influencing the adrenocorticotropin test: role of contemporary cortisol assays, body composition, and oral contraceptive agents

    DEFF Research Database (Denmark)

    Klose, Marianne; Lange, Martin; Rasmussen, Aase Krogh

    2007-01-01

    CONTEXT: The normal cortisol response to an ACTH test remains inconsistently defined, possibly caused by various subject- and test- condition-related factors. OBJECTIVE: Our objective was to evaluate the impact of newer automated immunoassays; gender, age, body composition, and endogenous sex......-hormone levels; corticosteroid-binding globulin levels; and test conditions (fasting/nonfasting, rest/intermittent exercise). METHODS: A 250-microg ACTH test (0800-1000 h) was performed in 100 unmedicated subjects, 13 women taking oral contraception (OC), and six men with nephrotic syndrome. Tests were performed...... cortisol (P>0.1). CONCLUSION: The normal response to an ACTH test is assay specific, even with newer methods, and this also applies to calculated free cortisol. Both total cortisol and calculated free cortisol were severely affected by OC, and the test is therefore only reliable if OC has been discontinued...

  8. Effect of cortisol on muscle sympathetic nerve activity in Pima Indians and Caucasians

    DEFF Research Database (Denmark)

    Vozarova, Barbora; Weyer, Christian; Snitker, Soren

    2003-01-01

    . Although glucocorticoids inhibit SNS activity, Pima Indians are not hypercortisolemic compared with Caucasians. This does not exclude the possibility that the SNS is more responsive to an inhibitory effect of cortisol in the former than in the latter group. We measured fasting plasma ACTH and cortisol...... (metyrapone) followed by cortisol replacement (hydrocortisone) on plasma ACTH, cortisol, and MSNA. There were no ethnic differences in fasting plasma ACTH or cortisol, but MSNA adjusted for percent body fat was lower in Pimas than in Caucasians (P cortisol...... to a tonic inhibitory effect of cortisol. However, an acute release of cortisol is likely to more effectively contain sympathoexcitation during stress in Pima Indians than in Caucasians, which may be an important mechanism of cardioprotection in this Native American population....

  9. A morphometric analysis of adrenocortical actin localized by immunoelectron microscopy: the effect of adrenocorticotropin.

    Science.gov (United States)

    Loesser, K E; Malamed, S

    1987-10-01

    The localization of actin and the effect of ACTH on its concentration was examined in freshly isolated rat adrenocortical cells. Lowicryl K4M-embedded cells were used for the immunoelectron localization of actin; gold was used as a label for immunoreactive sites. Actin was at least 4 times as concentrated at the cortical cytoplasm as in the lipid droplets and at least 5 times as concentrated in the microvilli as in the lipid droplets. ACTH stimulation approximately doubled the concentration of actin in the cortical cytoplasm and increased by 50% the concentration of actin in the microvilli. The microvillar contribution to the cell surface area was 40% higher in ACTH-stimulated cells than it was in unstimulated cells. These results provide quantitative evidence suggesting that actin and the microvilli participate in steroid secretion by the adrenocortical cell.

  10. Isolated adrenocorticotropin deficiency presenting as primary infertility.

    Science.gov (United States)

    Atkin, S L; Masson, E A; White, M C

    1995-06-01

    A 31 year old female presented with primary infertility and gave a two year history of amenorrhea without symptoms or signs of endocrine dysfunction. Examination was normal and investigation showed low oestradiol and progesterone levels with decreased LH pulsatility. The cortisol responses were impaired following hypoglycaemic stress and a short synacthen test, but the cortisol response to a prolonged synacthen test was normal. An inadequate ACTH response to CRF testing confirmed the diagnosis of isolated ACTH deficiency. Hydrocortisone therapy was followed by an ovulatory menstrual cycle. Amenorrhea again ensued following the reduction of the steroid dose and normal menses resumed on normal steroid replacement therapy. Six hourly gonadotrophin pulsatility showed a significant increase in both pulse amplitude and mean LH and FSH levels following steroid treatment. Isolated ACTH deficiency is a rare but treatable cause of hypogonadism and infertility, and this case gives further insight on the role of cortisol on the hypothalamo-pituitary gonadal axis.

  11. How should we interrogate the hypothalamic-pituitary-adrenal axis in patients with suspected hypopituitarism?

    Science.gov (United States)

    Garrahy, Aoife; Agha, Amar

    2016-06-17

    Hypopituitarism is deficiency of one or more pituitary hormones, of which adrenocorticotrophic hormone (ACTH) deficiency is the most serious and potentially life-threatening. It may occur in isolation or, more commonly as part of more widespread pituitary failure. Diagnosis requires demonstration of subnormal cortisol rise in response to stimulation with hypoglycemia, glucagon, ACTH(1-24) or in the setting of acute illness. The choice of diagnostic test should be individualised for the patient and clinical scenario. A random cortisol and ACTH level may be adequate in making a diagnosis in an acutely ill patient with a suspected adrenal crisis e.g. pituitary apoplexy. Often however, dynamic assessment of cortisol reserve is needed. The cortisol response is both stimulus and assay- dependent and normative values should be derived locally. Results must be interpreted within clinical context and with understanding of potential pitfalls of the test used.

  12. Observations on the ligand selectivity of the melanocortin 2 receptor.

    Science.gov (United States)

    Veo, Kristopher; Reinick, Christina; Liang, Liang; Moser, Emily; Angleson, Joseph K; Dores, Robert M

    2011-05-15

    The melanocortin 2 receptor (MC2R) is unique in terms of ligand selectivity and in vitro expression in mammalian cell lines as compared to the other four mammalian MCRs. It is well established that ACTH is the only melanocortin ligand that can activate the ACTH receptor (i.e., melanocortin 2 receptor). Recent studies have provided new insights into the presence of a common binding site for the HFRW motif common to all melanocortin ligands. However, the activation of the melanocortin 2 receptor requires an additional amino acid motif that is only found in the sequence of ACTH. This mini-review will focus on these two topics and provide a phylogenetic perspective on the evolution of MC2R ligand selectivity.

  13. A Case of Paraneoplastic Cushing Syndrome Presenting as Hyperglycemic Hyperosmolar Nonketotic Syndrome

    Directory of Open Access Journals (Sweden)

    Christina E. Brzezniak

    2017-04-01

    Full Text Available Carcinoid tumors are neuroendocrine tumors that mainly arise in the gastrointestinal tract, lungs, and bronchi. Bronchopulmonary carcinoids have been associated with Cushing syndrome, which results from ectopic adrenocorticotrophic hormone (ACTH secretion. We report the case of a 65-year-old man, a colonel in the US Air Force, with metastatic bronchopulmonary carcinoid tumors treated on a clinical trial who was hospitalized for complaints of increasing thirst, polydipsia, polyuria, weakness, and visual changes. Decompensated hyperglycemia suggested a diagnosis of hyperglycemic hyperosmolar nonketotic syndrome (HHNS. Additional findings, which included hypokalemia, hypernatremia, hypertension, metabolic alkalosis, moon facies, and striae, raised a red flag for an ectopic ACTH syndrome. Elevated ACTH levels confirmed Cushing syndrome. Treatment with a fluid replacement and insulin drip resulted in immediate symptomatic improvement. Cushing syndrome should be considered in carcinoid patients with physical stigmata such as moon facies and striae. HHNS may be the presenting clinical feature in patients with impaired glucose metabolism.

  14. Alpha-amidated peptides derived from pro-opiomelanocortin in normal human pituitary

    DEFF Research Database (Denmark)

    Fenger, M; Johnsen, A H

    1988-01-01

    Normal human pituitaries were extracted in boiling water and acetic acid, and the alpha-amidated peptide products of pro-opiomelanocortin (POMC), alpha-melanocyte-stimulating hormone (alpha MSH), gamma-melanocyte-stimulating hormone (gamma 1MSH), and amidated hinge peptide (HP-N), as well...... as their glycine-extended precursors, were characterized by sequence-specific radioimmunoassays, gel-chromatography, h.p.l.c. and amino acid sequencing. alpha MSH and gamma 1MSH constituted 0.27-1.32% and 0.10-5.10%, respectively, of the POMC-derived products [calculated as the sum of adrenocorticotropic hormone...... (ACTH)-(1-39), ACTH-(1-14) and alpha MSH immunoreactivity]. alpha MSH and ACTH-(1-14) were only present in non- or mono-acetylated forms. Only large forms of gamma 1MSH and gamma 2MSH were present in partly glycosylated states. The hinge peptides were amidated to an extent two to three orders...

  15. Ontogenetic studies of tolerance development: effects of chronic morphine on the hypothalamic-pituitary-adrenal axis.

    Science.gov (United States)

    Little, P J; Kuhn, C M

    1995-11-01

    Endogenous opiates are important regulators of the hypothalamic-pituitary-adrenal (HPA) axis in rats. Tolerance clearly develops to morphine-induced stimulation of the HPA axis in adult rats (Ignar and Kuhn 1990). The goal of the present study was to determine whether tolerance to morphine-induced stimulation of the HPA axis developed in neonatal and weanling rats treated chronically with morphine. Rats were injected with morphine or saline between days 4-8 postnatal (pups) or days 21-25 (weanlings) and tolerance assessed by determining dose-response curves for ACTH and corticosterone secretion following an acute morphine challenge. Weanlings displayed marked tolerance to the stimulation of ACTH and corticosterone secretion by morphine. Tolerance was also observed in pups to morphine-stimulated ACTH and corticosterone release. These findings suggest that the relative adaptability of the HPA axis to chronic morphine in neonatal and weanling rats is similar.

  16. Changes in the maternal hypothalamic-pituitary-adrenal axis during the early puerperium may be related to the postpartum 'blues'.

    Science.gov (United States)

    O'Keane, V; Lightman, S; Patrick, K; Marsh, M; Papadopoulos, A S; Pawlby, S; Seneviratne, G; Taylor, A; Moore, R

    2011-11-01

    Most women experience time-limited and specific mood changes in the days after birth known as the maternity blues (Blues). The maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes gradual changes during pregnancy because of an increasing production of placental corticotrophin-releasing hormone (CRH). The abrupt withdrawal of placental CRH at birth results in a re-equilibration of the maternal HPA axis in the days post-delivery. These changes may be involved in the aetiology of the Blues given the central role of the HPA axis in the aetiology of mood disorders in general, and in perinatal depression in particular. We aimed to test the novel hypothesis that the experience of the Blues may be related to increased secretion of hypothalamic adrenocorticotrophic hormone (ACTH) secretagogue peptides, after the reduction in negative-feedback inhibition on the maternal hypothalamus caused by withdrawal of placental CRH. We therefore examined hormonal changes in the HPA axis in the days after delivery in relation to daily mood changes: our specific prediction was that mood changes would parallel ACTH levels, reflecting increased hypothalamic peptide secretion. Blood concentrations of CRH, ACTH, cortisol, progesterone and oestriol were measured in 70 healthy women during the third trimester of pregnancy, and on days 1-6 post-delivery. Blues scores were evaluated during the postpartum days. Oestriol, progesterone and CRH levels fell rapidly from pregnancy up to day 6, whereas cortisol levels fell modestly. ACTH concentrations declined from pregnancy to day 3 post-delivery and thereafter increased up to day 6. Blues scores increased, peaking on day 5, and were positively correlated with ACTH; and negatively correlated with oestriol levels during the postpartum days, and with the reduction in CRH concentrations from pregnancy. These findings give indirect support to the hypothesis that the 'reactivation' of hypothalamic ACTH secretagogue peptides may be involved in the

  17. Effects of intracerebroventricular injection of histamine and related compounds on corticosterone release in rats.

    Science.gov (United States)

    Tsujimoto, S; Okumura, Y; Kamei, C; Tasaka, K

    1993-07-01

    1. The effects of intracerebroventricular (i.c.v.) injection of histamine and related compounds on plasma adrenocorticotrophic hormone (ACTH) and corticosterone concentrations were studied in conscious rats. 2. Histamine at doses of 5-20 micrograms kg-1 rapidly increased plasma ACTH and corticosterone concentrations almost simultaneously, and subsequent courses were also similar to each other. However, in the case of CRF-41 (i.v.), the plasma ACTH concentration first increased followed by an increase in plasma corticosterone concentration. Even in hypophysectomized rats, a significant increase in plasma corticosterone concentration was induced by histamine at doses of 20 and 50 micrograms kg-1. 3. Histamine at doses of 10 and 20 micrograms kg-1 elicited an increase in the amplitude of adrenal nerve activity, and electrical stimulation to the adrenal nerves resulted in an increase in plasma corticosterone concentration. 4. Both H1-agonist (2-methylhistamine) and H2-agonists (4-methylhistamine and impromidine) also induced similar effects to those of histamine. Pretreatment with pyrilamine caused an inhibition of histamine-induced increase in plasma ACTH and corticosterone concentrations, while both cimetidine and ranitidine failed to inhibit this effect. However, both H2-blockers were effective in inhibiting the 4-methylhistamine-induced elevation of plasma ACTH and corticosterone concentrations. 5. Neither (R)-alpha-methylhistamine nor thioperamide had a significant effect, indicating that the H3-receptor is not involved in the histamine-induced increase in plasma ACTH and corticosterone concentrations. 6. From these findings, it was concluded that (1) electrical signals transmitted from the brain to the adrenal gland through the neurones may be involved in the rapid corticosterone release induced by histamine, and (2) not only H1- but also H2-receptors are implicated in histamine-induced hormone secretions in rats, though the contribution of the H2-receptor is

  18. Proteomic analysis of adrenocorticotropic hormone treatment of an infantile spasm model induced by N-methyl-D-aspartic acid and prenatal stress.

    Directory of Open Access Journals (Sweden)

    Jing Wang

    Full Text Available Infantile spasms is an age-specific epileptic syndrome associated with poor developmental outcomes and poor response to nearly all traditional antiepileptic drugs except adrenocorticotropic hormone (ACTH. We investigated the protective mechanism of ACTH against brain damage. An infantile spasm rat model induced by N-methyl-D-aspartate (NMDA in neonate rats was used. Pregnant rats were randomly divided into the stress-exposed and the non-stress exposed groups, and their offspring were randomly divided into ACTH-treated spasm model, untreated spasm model, and control groups. A proteomics-based approach was used to detect the proteome differences between ACTH-treated and untreated groups. Gel image analysis was followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric protein identification and bioinformatics analysis. Prenatal stress exposure resulted in more severe seizures, and ACTH treatment reduced and delayed the onset of seizures. The most significantly up-regulated proteins included isoform 1 of tubulin β-5 chain, cofilin-1 (CFL1, synaptosomal-associated protein 25, malate dehydrogenase, N(G,N(G-dimethylarginine dimethylaminohydrolase 1, annexin A3 (ANXA3, and rho GDP-dissociation inhibitor 1 (ARHGDIA. In contrast, tubulin α-1A chain was down-regulated. Three of the identified proteins, ARHGDIA, ANXA3, and CFL1, were validated using western blot analysis. ARHGDIA expression was assayed in the brain samples of five infantile spasm patients. These proteins are involved in the cytoskeleton, synapses, energy metabolism, vascular regulation, signal transduction, and acetylation. The mechanism underlying the effects of ACTH involves the molecular events affected by these proteins, and protein acetylation is the mechanism of action of the drug treatment.

  19. Etiology and clinical profile of patients with Cushing's syndrome: A single center experience

    Science.gov (United States)

    Ammini, Ariacherry C.; Tandon, Nikhil; Gupta, Nandita; Bhalla, Ashu Seith; Devasenaspathy, Kandaswamy; Kumar, Guresh; Sahoo, Jaiprakash P.; Chittawar, Sachin; Philip, Jim; Baruah, Manas P.; Dwarakanath, C. S.; Tripathi, Sudhir

    2014-01-01

    Background: There is little published literature on the profile of patients with Cushing's syndrome (CS) from India. The aim of this study was to compile data of CS patients treated at this hospital. Materials and Methods: Patients referred to the endocrine services of this hospital for diagnosis/treatment of CS from January 1985 to July 2012 were the subjects for this study. All patients had detailed medical history, physical examination and biochemical and hormonal assays (which changed with availability of tests and changing views). Assays for plasma adrenocorticotropic hormone (ACTH) (late 90s), salivary cortisol estimation, IJV sampling for ACTH and corticotrophin releasing hormone stimulation tests were added on later. Imaging included computed tomography (CT), magnetic resonance imaging (since the late 80's) and 68Ga DOTA-TOC/FDG PET-CT (2008). Results: Three hundred sixty-four patients (250 females, 114 males, age 6 months to 65 years, mean 28 years + 12 years) were diagnosed to have CS during this period. Two hundred and ninety-three patients (80.5%) were ACTH dependent (CD 215, ectopic ACTH syndrome 22, occult ACTH source 56) while 71 (19.5%) were ACTH independent (adrenal carcinoma 36, adenoma 30, primary pigmented nodular adrenal disease 4, AIMAH 1). Pituitary macro adenoma was seen in 14% of the CD cases. The most common presenting complaints were hypertension and diabetes mellitus. A total of 63% patients complained of weight gain while 15% had lost weight. Myopathy, infections, skeletal fractures and psychiatric problems were the other common observations in our patients. Conclusion: The clinical spectrum was broad. CD was the most common cause for CS. PMID:24701438

  20. Does orthostatic stress influence the neuroendocrine response to subsequent hypoglycemia in humans?

    Science.gov (United States)

    Radikova, Z; Penesova, A; Koska, J; Kvetnansky, R; Jezova, D; Huckova, M; Vigas, M; Macho, L

    2004-06-01

    Neuroendocrine response to stress stimuli is influenced by previous stimuli of different nature. The aim of the study was to test whether antecedent orthostatic stress may affect the neuroendocrine response to subsequent hypoglycemia. A group of 12 (6 men, 6 women) nonobese, healthy volunteers aged 19 to 27 y (mean 24 +/- 0.8) participated in the study in two sessions: controlled insulin-induced hypoglycemia to 2.7 mmol/L for 15 min either with or without antecedent orthostatic stress (30 min of 60 degrees head-up tilt before insulin administration). Orthostatic stress caused a significant decrease in plasma volume (-9.6%; P < 0.001) and a significant increase in plasma renin activity, aldosterone, norepinephrine (P < 0.01), and adrenocorticotropic hormone (ACTH) concentrations (P < 0.05) in all subjects. Growth hormone response to hypoglycemia was diminished in women (P < 0.01). The epinephrine response to hypoglycemia was diminished in women in comparison to men (P < 0.001), but was unaffected by antecedent orthostatic stress. Hypoglycemia failed to induce the ACTH release after its elevation during orthostatic stress. ACTH response to moderate hypoglycemia without previous orthostatic stress was evident only in men in comparison to women (P < 0.05). We conclude that the epinephrine, growth hormone, and ACTH responses to hypoglycemia were diminished in women. Except ACTH, the neuroendocrine response to mild hypoglycemia was not affected by previous orthostatic stress in healthy subjects. In the case of ACTH, the first stress stimulus is consequential for the subsequent response of this hormone, probably due to short-loop negative feedback effects.

  1. THE CHARACTERISTICS OF ENDOGENOUS OUABAIN SECRETIONFROM CULTURED BOVINE ADRENOCORTICAL CELLS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To compare the characteristics of endogenous ouabain(EO) secretion with the other adrenocortical hormones and determine the effects of angiotensin Ⅰ (Ang Ⅰ ), and adrenocorticotrophin(ACTH) on the secretion of EO. Methods EO was measured by radioimmunoassay from primary cultured bovine adrenocotical cells (BAC). Results ①Ouabain was determined in the media of cultured BAC. Both EO and aldosterone secretion were decreased from the outer to inner layer of the cultured adrenal cortex, and the responses to Ang Ⅰ and ACTH were higher than that in the mid layer (P <0. 05) and inner layer (P <0. 01). Cortisol secretion was activated by Ang Ⅱ or ACTH was significantly higher in the mid layer and in the inner layer than that in the outer layer. ②The time-course experiment showed that the gradually rising amounts of aldosterone and cortisol could be determined dur ing the continuous incubation to 48h with or without Ang Ⅰ or ACTH. However, EO did not increase continuously af ter 24h of incubation in the basal secreting situation and after 12h of incubation in the stimulating situation by Ang Ⅱ or ACTH. ③There were obvious drops in aldosterone and cortisol secretion from 3rd day during a 21 day-period cell culture, but the peak secretion of ouabain was in 7th day. Conclusion It suggests that the secretory mechanism might be different between EO and aldosterone or cortisol. Also, Ang Ⅱ and ACTH might be involved in the regulation of EO secretion.

  2. Tumor necrosis factor alpha affect hydrocortisone expression in mice adrenal cortex cells mainly through tumor necrosis factor alpha-receptor 1

    Institute of Scientific and Technical Information of China (English)

    XIA Hai-ming; FANG Yuan; HUANG Pei-lin

    2011-01-01

    Background Tumor necrosis factor alpha (TNF-α) is important in promoting relative adrenal insufficiency (RAI) due to systemic inflammatory response syndrome (SIRS).We identified the TNF-α receptor involved in the inhibition of adrenal corticotrophin (ACTH)-stimulated hydrocortisone release by studying the expression of TNF-α receptors in adrenal cortex Y1 cells and the effect of downregulating TNF receptors on ACTH-stimulated hydrocortisone release.Methods We used real-time PCR and immunocytochemistry to evaluate the expression of TNF receptors on Y1 cells.TNF-receptor 1 (TNF-R1) DNA fragments corresponding to the short hairpin RNA (shRNA)-sequences were synthesized and cloned into pcDNATM 6.2-GW/EmGFP expression vector.Knockdown efficiency of TNF-R1 expression was evaluated in miRNA transfected and mock-miRNA transfected Y1 cells by quantitative real-time PCR (Q-PCR).Hydrocortisone expression levels were determined in TNF-R1-knockdown and control Y1 cells treated with TNF-α and ACTH.Results Mouse adrenal cortex Y1 cells were positive for type I TNF-R1,but not type Ⅱ TNF-receptor (TNF-R2).Blocking TNF-R1 expression resulted in loss of TNF-α-mediated inhibition of ACTH-stimulated hydrocortisone expression,suggesting a role for the TNF-R1 related signaling pathway in ACTH-stimulated hydrocortisone synthesis.Conclusion The inhibitory effect of TNF-α on ACTH-stimulated hydrocortisone synthesis was mediated via TNF-R1 in adrenal cortex.

  3. 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.

    Science.gov (United States)

    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.

  4. Heart failure caused by atrial fibrillation in a patient with isolated adrenocorticotropic hormone deficiency and hashimoto′s thyroiditis

    Directory of Open Access Journals (Sweden)

    Ryo Maemura

    2014-01-01

    Full Text Available We report the case of a 75-year-old female patient with a history of Hashimoto′s thyroiditis who presented with congestive heart failure caused by atrial fibrillation associated with isolated adrenocorticotropic hormone (ACTH deficiency. This is the first case of the combination of these complex conditions. Clinical conditions in a patient with isolated ACTH deficiency and Hashimoto′s thyroiditis can be variable. Thus, it is sometimes difficult to establish a diagnosis. The mechanism underlying heart failure may be complex in some cases. Various conditions can affect patients simultaneously. Therefore, making a proper diagnosis is necessary to improve the patient′s prognosis.

  5. Autonomic nervous system function in patients with functional abdominal pain. An experimental study

    DEFF Research Database (Denmark)

    Jørgensen, L S; Christiansen, P; Raundahl, U

    1993-01-01

    disturbed in 22 patients with functional abdominal pain (functional group) as compared with 14 healthy controls (healthy group) and 26 patients with organic abdominal pain (organic group) due to duodenal ulcer (DU), gallstones, or urinary tract calculi. Plasma adrenocorticotrophic hormone (ACTH) and serum...... cortisol measurements were included, to assess the pituitary-adrenocortical axis. Heart rate, systolic blood pressure, and plasma adrenaline increased significantly in all groups in response to a stress test (mental arithmetic). Plasma noradrenaline increased in the DU patients only, and plasma ACTH...

  6. Genetic polymorphisms of MC2R gene associated with responsiveness to adrenocorticotropic hormone therapy in infantile spasms

    Institute of Scientific and Technical Information of China (English)

    LIU Zhan-li; HE Bing; FANG Fang; TANG Cai-yun; ZOU Li-ping

    2008-01-01

    Background Infantile spasms is a severe epileptic encephalopathy,which is refractory to conventional antiepileptic drugs.Adrenocorticotropic hormone (ACTH) has been the major therapy for infantile spasms;however,ACTH therapy is ineffective for some patients.The variations in the receptor genes can contribute to antiepileptic drug resistance.This study was to elucidate the possible associations between the variations of the MC2R gene and ACTH responsiveness in patients with infantile spasms.Methods We screened for variations in the promoter and coding region of the MC2R gene in 91 Chinese patients with infantile spasms and 94 controls,using PCR and a direct sequencing method.The frequencies of the genotypes,alleles and reconstructed haplotypes were analyzed in the cases and controls.The association between ACTH responsiveness and genetic variations of the MC2R gene was also assessed.Results Four single nucleotide polymorphisms (SNPs) were identified in the MC2R promoter,one of which was a novel specimen at position-2 from the transcription start site ATT,-2T>C.Three SNPs (rs1893220,rs2186944 and -2T>C)showed a significant difference between the cases and controls (P<0.05 for all).The frequency of the common TCCT haplotype carrying four-SNP major alleles was significantly lower in the cases (39%) than in the controls (60%)(P=0.00003).The homozygous carriers of the TCCT haplotype had a much lower relative risk than the non-carriers (RR=0.42,95%CI 0.26-0.70,P=0.0001).ACTH responsiveness was strongly associated with the TCCT haplotype (P=0.000082).Compared with non-carriers of the TCCT haplotype,the homozygous and heterozygous carders were more responsive to ACTH therapy (P=0.0002;P=0.0003,respectively).Conclusions Our results indicated that the TCCT haplotype in the MC2R promoter is strongly associated with the responsiveness of the ACTH therapy performed on patients with infantile spasms.The polymorphisms of the MC2R promoter might be one important factor that

  7. Simulation Time History and Access Time History Programs (Users Manual)

    Science.gov (United States)

    1993-02-01

    Motion program, SMP81. 1 Data Set 10. Run Innut r - FORMAT (A) No variables, blank line used for spacing. Sond Line - Free Format (1) NRUNS, integer...ACTH Run First Line - FORMAT (A) No variables, blank line used for spacing. sond ine - Format (15X,I5) (1) STARTRUN, integer, columns 16-20, start ACTH...C DIMENSIONS COMMON DUMMY ,USCS,IvS,IvuS,PAGE,ECS,DELL,DISP, 2 CLR,YS,N8,N, Samplerate,Dt, Runnumber

  8. Copeptin during rest and exercise in major depression

    DEFF Research Database (Denmark)

    Krogh, Jesper; Gøtze, Jens Peter; Jørgensen, Martin Balslev

    2013-01-01

    High vasopressin levels and a correlation between vasopressin and cortisol has been observed in patients with depression. The aim was to assess copeptin, the c-terminal of provasopressin, and the association between cortisol, adrenocorticotropic hormone (ACTH) and copeptin in patients with depres......High vasopressin levels and a correlation between vasopressin and cortisol has been observed in patients with depression. The aim was to assess copeptin, the c-terminal of provasopressin, and the association between cortisol, adrenocorticotropic hormone (ACTH) and copeptin in patients...... with depression. Secondly, to examine the copeptin response to acute exercise and aerobic training....

  9. Adrenal androgen hyperresponsiveness to adrenocorticotropin in women with acne and/or hirsutism: adrenal enzyme defects and exaggerated adrenarche.

    Science.gov (United States)

    Lucky, A W; Rosenfield, R L; McGuire, J; Rudy, S; Helke, J

    1986-05-01

    To determine the adrenal contribution to elevated plasma androgens in 31 young hyperandrogenemic women with acne and/or hirsutism, we compared their responses to ACTH with those of 14 normal women. Each subject was given a low dose (10 micrograms/m2) of synthetic ACTH-(1-24) (Cortrosyn) after administration of 1.5 mg dexamethasone the night before the test. Thirty and 60 min responses of plasma 17 alpha-hydroxypregnenolone (17-Preg), 17 alpha-hydroxyprogesterone, (17-prog), dehydroepiandrosterone (DHEA), androstenedione, 11-deoxycortisol, and cortisol were measured. Eighteen (58%) patients had increased responses of at least one 17-ketosteroid or adrenal androgen precursor. All patients had cortisol responses within the range of those of the 14 normal subjects. Nine patients (29%) had evidence of steroid biosynthetic enzyme deficiencies, either mild congenital adrenal hyperplasia or the heterozygote state; after ACTH, 4 of these patients had elevated 17-prog in the range of values in heterozygote carriers of 21-hydroxylase deficiency, 2 had elevated levels of 11-deoxycortisol compatible with 11 beta-hydroxylase deficiency, and 3 had elevated levels of 17-Preg and DHEA, suggestive of 3 beta-hydroxysteroid dehydrogenase deficiency. Another 9 subjects (29%) had 17-ketosteroid (DHEA and/or androstenedione) hyperresponsiveness to ACTH with associated elevated 17-Preg responses. As a group, their patterns suggested relatively deficient 3 beta-hydroxysteroid dehydrogenase and relatively hyperactive C lyase without impairment of cortisol secretion. This pattern resembles exaggerated adrenarche, and we postulate that these 9 patients have hyperplasia of the zona reticularis. Neither basal levels of plasma androgens (free testosterone and DHEA sulfate) nor menstrual history predicted which patients would have abnormal ACTH responses. Although 5 of 11 (45%) patients with acne alone had abnormal responses to ACTH, 10 of 14 patients with acne and hirsutism (71%) had abnormal

  10. Abnormal release of incretins and cortisol after oral glucose in subjects with insulin-resistant myotonic dystrophy

    DEFF Research Database (Denmark)

    Johansson, Asa; Olsson, Tommy; Cederquist, Kristina;

    2002-01-01

    OBJECTIVE: Although the incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), as well as glucagon and cortisol, are known to influence islet function, the role of these hormones in conditions of insulin resistance and development of type 2 diabetes is unknown...... response. Furthermore, cortisol and ACTH levels increased paradoxically in patients after glucose; this was more pronounced in patients with long CTG repeat expansions. CONCLUSIONS: This study showed that the GLP-1 and ACTH/cortisol responses to oral glucose are abnormal in insulin-resistant DM1 patients...

  11. A case of suspect “cyanosis”

    Directory of Open Access Journals (Sweden)

    Elisabetta Antonucci

    2013-05-01

    Full Text Available CLINICAL CASE A 70-year old woman was admitted to our hospital because of fever, asthenia and a suspected stroke. Her medical history showed a congenital cardiopathy (Patent Foramen Ovale, PFO. Skin and oral mucosa pigmentation, orthostatic hypotension, hypoglycemia and hyponatriemia arose the suspect of Addison’s disease. The diagnosis was confirmed by the evaluation of basal levels of plasma ACTH and serum cortisol, and serum cortisol levels after ACTH stimulation. Abdominal CT scan showed atrophy and calcification of adrenal glands. CONCLUSIONS In most cases, Addison’s disease is provoked by autoimmune destruction of the adrenal cortex; however, in our reported patient, tuberculosis could be a possible cause.

  12. Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection

    Directory of Open Access Journals (Sweden)

    McCann S.M.

    2000-01-01

    Full Text Available The release of adrenocorticotropin (ACTH from the corticotrophs is controlled principally by vasopressin and corticotropin-releasing hormone (CRH. Oxytocin may augment the release of ACTH under certain conditions, whereas atrial natriuretic peptide acts as a corticotropin release-inhibiting factor to inhibit ACTH release by direct action on the pituitary. Glucocorticoids act on their receptors within the hypothalamus and anterior pituitary gland to suppress the release of vasopressin and CRH and the release of ACTH in response to these neuropeptides. CRH neurons in the paraventricular nucleus also project to the cerebral cortex and subcortical regions and to the locus ceruleus (LC in the brain stem. Cortical influences via the limbic system and possibly the LC augment CRH release during emotional stress, whereas peripheral input by pain and other sensory impulses to the LC causes stimulation of the noradrenergic neurons located there that project their axons to the CRH neurons stimulating them by alpha-adrenergic receptors. A muscarinic cholinergic receptor is interposed between the alpha-receptors and nitric oxidergic interneurons which release nitric oxide that activates CRH release by activation of cyclic guanosine monophosphate, cyclooxygenase, lipoxygenase and epoxygenase. Vasopressin release during stress may be similarly mediated. Vasopressin augments the release of CRH from the hypothalamus and also augments the action of CRH on the pituitary. CRH exerts a positive ultrashort loop feedback to stimulate its own release during stress, possibly by stimulating the LC noradrenergic neurons whose axons project to the paraventricular nucleus to augment the release of CRH.

  13. Circulating β-endorphin, adrenocorticotrophic hormone and cortisol levels of stallions before and after short road transport: stress effect of different distances

    Directory of Open Access Journals (Sweden)

    Grasso Loredana

    2008-03-01

    Full Text Available Abstract Background Since transport evokes physiological adjustments that include endocrine responses, the objective of this study was to examine the responses of circulating β-endorphin, adrenocorticotrophic hormone (ACTH and cortisol levels to transport stress in stallions. Methods Forty-two healthy Thoroughbred and crossbred stallions were studied before and after road transport over distances of 100, 200 and 300 km. Blood samples were collected from the jugular vein: first in a single box immediately before loading (pre-samples, then immediately after transport and unloading on arrival at the breeding stations (post-samples. Results An increase in circulating β-endorphin levels after transport of 100 km (P P P P P > 0.05 between horses of different ages and different breeds were observed for β-endorphin, ACTH and cortisol levels. Conclusion The results obtained for short term transportation of stallions showed a very strong reaction of the adrenocortical system. The lack of response of β-endorphin after transport of 200–300 km and of ACTH after transport of 300 km seems to suggest a soothing effect of negative feedback of ACTH and cortisol levels.

  14. The stress system in the human brain in depression and neurodegeneration.

    NARCIS (Netherlands)

    Swaab, D.F.; Bao, A.-M.; Lucassen, P.J.

    2005-01-01

    Corticotropin-releasing hormone (CRH) plays a central role in the regulation of the hypothalamic-pituitary-adrenal (HPA)-axis, i.e., the final common pathway in the stress response. The action of CRH on ACTH release is strongly potentiated by vasopressin, that is co-produced in increasing amounts wh

  15. The stress system in the human brain in depression and neurodegeneration

    NARCIS (Netherlands)

    Swaab, D.F.; Bao, A.M; Lucassen, P.J.

    2005-01-01

    Corticotropin-releasing hormone (CRH) plays a central role in the regulation of the hypothalamic-pituitary-adrenal (HPA)-axis, i.e., the final common pathway in the stress response. The action of CRH on ACTH release is strongly potentiated by vasopressin, that is co-produced in increasing amounts wh

  16. ATRAZINE DOES NOT INDUCE GASTROINTESTINAL DISCOMFORT (PICA) IN RATS AT DOSES THAT INCREASE HPA-AXIS ACTIVATION AND CAUSE CONDITIONED TASTE AVERSION.

    Science.gov (United States)

    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 ...

  17. Space Flight Research Relevant to Health, Physical Education, and Recreation. With Particular Reference to Skylab’s Life Science Experiments

    Science.gov (United States)

    1979-06-01

    15. 1 CDR=Commander. - SPT=Scientist Pilot. 9 PLT=Pilot. potatoes (mashed), rice krispies, salmon salad, sausage patties, shrimp cocktail...sodium, potas- sium, creatinine, growth hormone, ACTH, calcitonin , and aldosterone. These data significant in differentiating...or a wasting away. Blood plasma. The liquid component of the blood in which the corpuscles are suspended. Calcitonin . Hormone involved in calcium

  18. Pro-opiomelanocortin-derived peptides in the pig pituitary: alpha- and gamma 1-melanocyte-stimulating hormones and their glycine-extended forms

    DEFF Research Database (Denmark)

    Fenger, M

    1988-01-01

    to the neurointermediate lobe (19.8 nmol POMC/anterior lobe vs 7.0 nmol/neurointermediate lobe). In the neurointermediate lobe 93% of POMC was processed to alpha-melanocyte-stimulating hormone (alpha-MSH) and analogs exclusively of low molecular weight. Most of the remaining adrenocorticotropic hormone (ACTH...

  19. Characterization of murine melanocortin receptors mediating adipocyte lipolysis and examination of signalling pathways involved

    DEFF Research Database (Denmark)

    Møller, Cathrine Laustrup; Raun, Kirsten; Jacobsen, Marianne Lambert

    2011-01-01

    The melanocortin receptors (MCRs) belong to the G-protein coupled receptors (family A). So far, 5 different subtypes have been described (MC1R-MC5R) and of these MC2R and MC5R have been proposed to act directly in adipocytes and regulate lipolysis in rodents. Using ACTH and a-melanocyte stimulating...

  20. The orphan G protein-coupled receptor GPR139 is activated by the peptides

    DEFF Research Database (Denmark)

    Jensen, Anne Cathrine Nøhr; Shehata, Mohamed A; Hauser, Alexander S

    2017-01-01

    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...

  1. The burden of Cushing's disease: Clinical and health-related quality of life aspects

    NARCIS (Netherlands)

    R.A. Feelders (Richard); S.J. Pulgar (S.); A. Kempel (A.); A.M. Pereira (Alberto)

    2012-01-01

    textabstractObjective: Cushing's disease (CD) is a rare endocrine disorder characterized by excess secretion of ACTH due to a pituitary adenoma. Current treatment options are limited and may pose additional risks. A literature review was conducted to assess the holistic burden of CD. Design: Studies

  2. Amidated joining peptide in the human pituitary, gut, adrenal gland and bronchial carcinoids. Immunocytochemical and immunochemical evidence

    DEFF Research Database (Denmark)

    Bjartell, A; Fenger, M; Ekman, R;

    1990-01-01

    .g., ACTH, beta-endorphin, Pro-tau-MSH, in the pituitary gland and adrenal medulla. The JP-N immunoreactive cells in the adrenal medulla were identified as a subpopulation of adrenaline-producing cells by means of an antiserum against phenylethanolamine N-methyltransferase. In the gut immunoreactive JP...

  3. 9.6.Adenohyphysis and neurohypophysis

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930250 Immunohistochemical and ultrastruc-tural study of plurihormonal pituitary adeno-mas.LIU Dongge (刘冬戈),et al.Dept Pathol,Beijing Hosp,Beijing,100730.Natl Med J Chin1993;73(4):223—225Thirty—eight cases of plurihormornal pituitaryadenomas containing growth hormone were de-tected by PAP technique for GH,PRL,ACTH,

  4. Effects of sex and early maternal abuse on adrenocorticotropin hormone and cortisol responses to the corticotropin-releasing hormone challenge during the first 3 years of life in group-living rhesus monkeys.

    Science.gov (United States)

    Sanchez, Mar M; McCormack, Kai; Grand, Alison P; Fulks, Richelle; Graff, Anne; Maestripieri, Dario

    2010-01-01

    In this study we investigated the development of the hypothalamic-pituitary-adrenal (HPA) axis in 21 group-living rhesus monkeys infants that were physically abused by their mothers in the first few months of life and in 21 nonabused controls. Cortisol and adrenocorticotropin hormone (ACTH) responses to a corticotropin-releasing hormone (CRH) challenge were assessed at 6-month intervals during the subjects' first 3 years of life. Abused infants exhibited greater cortisol responses to CRH than controls across the 3 years. Abused infants also exhibited blunted ACTH secretion in response to CRH, especially at 6 months of age. Although there were no significant sex differences in abuse experienced early in life, females showed a greater cortisol response to CRH than males at all ages. There were no significant sex differences in the ACTH response to CRH, or significant interactions between sex and abuse in the ACTH or cortisol response. Our findings suggest that early parental maltreatment results in greater adrenocortical, and possibly also pituitary, responsiveness to challenges later in life. These long-term alterations in neuroendocrine function may be one the mechanisms through which infant abuse results in later psychopathologies. Our study also suggests that there are developmental sex differences in adrenal function that occur irrespective of early stressful experience. The results of this study can enhance our understanding of the long-term effects of child maltreatment as well as our knowledge of the development of the HPA axis in human and nonhuman primates.

  5. Ectopic Cushing syndrome secondary to recurrent pancreatoblastoma in a child: Lessons learnt

    Directory of Open Access Journals (Sweden)

    Sajid S Qureshi

    2015-01-01

    Full Text Available Although rare, pancreatoblastoma is the most common pancreatic tumor in children. Cushing syndrome secondary to ectopic secretion of adrenocorticotropic hormone (ACTH from a pancreatoblastoma is very rare with only two previously reported cases. We present the management and the lesson learnt in a 3-year-old child with recurrent pancreatoblastoma with Cushing syndrome.

  6. Human adrenocorticotropin-secreting pituitary adenomas show frequent loss of heterozygosity at the glucocorticoid receptor gene locus

    NARCIS (Netherlands)

    N.A.T.M. Huizenga (Nannette); P. de Lange (Pieter); J.W. Koper (Jan); R.N. Clayton (Richard); W.E. Farrell (William); A-J. van der Lely (Aart-Jan); A.O. Brinkmann (Albert); F.H. de Jong (Frank); S.W.J. Lamberts (Steven)

    1998-01-01

    textabstractCorticotropinomas are characterized by a relative resistance to the negative feedback action of cortisol on ACTH secretion. In this respect there is a similarity with the clinical syndrome of cortisol resistance. As cortisol resistance can be caused by genetic abnormali

  7. Screening for GPR101 defects in pediatric pituitary corticotropinomas.

    Science.gov (United States)

    Trivellin, Giampaolo; Correa, Ricardo R; Batsis, Maria; Faucz, Fabio R; Chittiboina, Prashant; Bjelobaba, Ivana; Larco, Darwin O; Quezado, Martha; Daly, Adrian F; Stojilkovic, Stanko S; Wu, T John; Beckers, Albert; Lodish, Maya; Stratakis, Constantine A

    2016-03-09

    Cushing disease (CD) in children is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Germline or somatic mutations in genes such as MEN1, CDKIs, AIP, and USP8 have been identified in pediatric CD, but the genetic defects in a significant percentage of cases are still unknown. We investigated the orphan G protein-coupled receptor GPR101, a gene known to be involved in somatotropinomas, for its possible involvement in corticotropinomas. We performed GPR101 sequencing, expression analyses by RT-qPCR and immunostaining, and functional studies (cell proliferation, pituitary hormones secretion, and cAMP measurement) in a series of patients with sporadic CD secondary to ACTH-secreting adenomas in whom we had peripheral and tumor DNA (N=36). No increased GPR101 expression was observed in tumors compared to normal pituitary (NP) tissues, nor did we find a correlation between GPR101 and ACTH expression levels. Sequence analysis revealed a very rare germline heterozygous GPR101 variant (p.G31S) in one patient with CD. Overexpression of the p.G31S variant did not lead to increased growth and proliferation, although modest effects on cAMP signaling were seen. GPR101 is not overexpressed in ACTH-secreting tumors compared to NPs. A rare germline GPR101 variant was found in one patient with CD but in vitro studies did not support a consistent pathogenic effect. GPR101 is unlikely to be involved in the pathogenesis of CD.

  8. Is basal serum 17-OH progesterone a reliable parameter to predict nonclassical congenital adrenal hyperplasia in premature adrenarche?

    Science.gov (United States)

    Gönç, E Nazli; Ozön, Z Alev; Alikaşifoğlu, Ayfer; Engiz, Ozlem; Bulum, Burcu; Kandemir, Nurgün

    2011-01-01

    To determine the critical features for the diagnosis of nonclassical 21 hydroxylase deficiency (NC210HD) without performing adrenocorticotropic hormone (ACTH) test, we studied 186 cases with premature adrenarche. Clinical and laboratory features as well as basal 17-hydroxyprogesterone (17-OHP) were analyzed to determine factors important for differentiating NC21OHD. Overall, 6 patients (3.2%) had ACTH-stimulated 17-OHP > 10 ng/ml. A cutoff level of 2 ng/ml for basal 17-OHP was 66.7% sensitive and 78% specific for NC21OHD; however, a cutoff level of 1.55 ng/ml had higher sensitivity (83%) and specificity (70.6%). A cutoff of 1.55 ng/ml would lead to 31% of cases with premature adrenarche having to undergo ACTH test, and only one case would have been missed. That case had a bone age SDS > 2. Three cases out of five with a basal 17-OHP > 5 ng/ml had stimulated 17-OHP bone SDS > 2 in those with lower basal levels as a guide for carrying out an ACTH test may yield better results in the diagnosis of NC21OHD in the premature adrenarche population. A cutoff of 5 ng/ml for basal 17-OHP should not be used for diagnosis of NC21OHD.

  9. Hormonal regulation of lipoprotein lipase in adipose tissue (studies in the rat and in humans)

    NARCIS (Netherlands)

    M.G.A. Baggen (Marinus)

    1988-01-01

    textabstractCurrent data strongly suggest the most important role for insulin in the hormonal regulation of adipose tissue LPL activity. It is not clear from the literature what the role is of glucocorticoids in the regulation of the enzyme. Stress hormones as ACTH and adrenalin for example seem to

  10. Transcriptional activation of melanocortin 2 receptor accessory protein by PPARγ in adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Nam Soo; Kim, Yoon-Jin [Department of Biology, Research Institute for Basic Science, Kyung Hee University, Seoul 130-701 (Korea, Republic of); Cho, Si Young [R and D Center, Amore Pacific Corporation, Yongin-si, Gyeonggi-do 446-729 (Korea, Republic of); Lee, Tae Ryong, E-mail: trlee@amorepacific.com [R and D Center, Amore Pacific Corporation, Yongin-si, Gyeonggi-do 446-729 (Korea, Republic of); Kim, Sang Hoon, E-mail: shkim@khu.ac.kr [Department of Biology, Research Institute for Basic Science, Kyung Hee University, Seoul 130-701 (Korea, Republic of)

    2013-09-27

    Highlights: •MRAP enhanced HSL expression. •ACTH-mediated MRAP reduced glycerol release. •PPARγ induced MRAP expression. •PPARγ bound to the MRAP promoter. -- Abstract: Adrenocorticotropic hormone (ACTH) in rodents decreases lipid accumulation and body weight. Melanocortin receptor 2 (MC2R) and MC2R accessory protein (MRAP) are specific receptors for ACTH in adipocytes. Peroxisome proliferator-activated receptor γ (PPARγ) plays a role in the transcriptional regulation of metabolic pathways such as adipogenesis and β-oxidation of fatty acids. In this study we investigated the transcriptional regulation of MRAP expression during differentiation of 3T3-L1 cells. Stimulation with ACTH affected lipolysis in murine mature adipocytes via MRAP. Putative peroxisome proliferator response element (PPRE) was identified in the MRAP promoter region. In chromatin immunoprecipitation and reporter assays, we observed binding of PPARγ to the MRAP promoter. The mutagenesis experiments showed that the −1209/−1198 region of the MRAP promoter could function as a PPRE site. These results suggest that PPARγ is required for transcriptional activation of the MRAP gene during adipogenesis, which contributes to understanding of the molecular mechanism of lipolysis in adipocytes.

  11. Composition of culture media for steroid hormone secretion by murine adrenal tumor cells, Y-1 clone.

    Directory of Open Access Journals (Sweden)

    Ichikawa,Yoshiko

    1989-04-01

    Full Text Available Murine adrenal tumor cells (Y-1 clone were stimulated by adrenocorticotropic hormone (ACTH and cyclic adenosine 3',5'-monophosphate (cyclic AMP to produce steroid hormone (delta 4, 3-keto steroids. The steroids were secreted into the medium immediately after synthesis. The optimum concentrations of ACTH and cyclic AMP for stimulation of steroid production were 10(-2 U/ml and 1.0 mM, respectively. In serum-free medium, ACTH and cyclic AMP stimulated steroidogenesis in Y-1 cells, but the amount of steroid hormone in the culture medium was low. However, a high level of steroid production was maintained with medium containing 10 mg/ml bovine serum albumin (BSA. In culture medium containing a higher concentration of BSA, Y-1 cells did not become spherical as is usually the case when steroid production is stimulated by ACTH or cyclic AMP. The morphological changes did not always correlate with steroid secretion by Y-1 cells.

  12. Hyperprolactinemia and male reproductive functions

    NARCIS (Netherlands)

    R.F.A. Weber (Robert)

    1983-01-01

    textabstractIn this thesis some effects of PRL on reproductive functions have been investigated PRL-secreting pituitary adenoma. animal model has been used: For in men with a comparison an In. rats hyperprolactinemia has been induced by sub-cutaneous inoculation of a PRL- and ACTH-secreting transpla

  13. Lack of Ubiquitin Specific Protease 8 (USP8) Mutations in Canine Corticotroph Pituitary Adenomas

    NARCIS (Netherlands)

    Sbiera, Silviu; Tryfonidou, Marianna A; Weigand, Isabel; Grinwis, Guy C M; Broeckx, Bart; Herterich, Sabine; Allolio, Bruno; Deutschbein, Timo; Fassnacht, Martin; Meij, Björn P

    2016-01-01

    PURPOSE: Cushing's disease (CD), also known as pituitary-dependent hyperadrenocorticism, is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumours. Affected humans and dogs have similar clinical manifestations, however, the incidence of the canine disease is thousand-fold higher. T

  14. Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics

    Directory of Open Access Journals (Sweden)

    Carlotta Pozza

    2012-01-01

    Full Text Available Cushing’s syndrome (CS is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing’s disease, CD or an ectopic source (ectopic ACTH secretion, EAS. The remaining causes (20% are ACTH independent. As soon as the diagnosis is established, the therapeutic goal is the removal of the tumor. Whenever surgery is not curative, management of patients with CS requires a major effort to control hypercortisolemia and associated symptoms. A multidisciplinary approach that includes endocrinologists, neurosurgeons, oncologists, and radiotherapists should be adopted. This paper will focus on traditional and novel medical therapy for aggressive ACTH-dependent CS. Several drugs are able to reduce cortisol levels. Their mechanism of action involves blocking adrenal steroidogenesis (ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidate or inhibiting the peripheral action of cortisol through blocking its receptors (mifepristone “RU-486”. Other drugs include centrally acting agents (dopamine agonists, somatostatin receptor agonists, retinoic acid, peroxisome proliferator-activated receptor γ “PPAR-γ” ligands and novel chemotherapeutic agents (temozolomide and tyrosine kinase inhibitors which have a significant activity against aggressive pituitary or ectopic tumors.

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

    Science.gov (United States)

    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.

  16. Temozolomide and pasireotide treatment for aggressive pituitary adenoma: expertise at a tertiary care center.

    Science.gov (United States)

    Ceccato, Filippo; Lombardi, Giuseppe; Manara, Renzo; Emanuelli, Enzo; Denaro, Luca; Milanese, Laura; Gardiman, Marina Paola; Bertorelle, Roberta; Scanarini, Massimo; D'Avella, Domenico; Occhi, Gianluca; Boscaro, Marco; Zagonel, Vittorina; Scaroni, Carla

    2015-03-01

    Aggressive pituitary adenomas (PAs) are clinically challenging for endocrinologists and neurosurgeons due to their locally invasive nature and resistance to standard treatment (surgery, medical or radiotherapy). Two pituitary-directed drugs have recently been proposed: temozolomide (TMZ) for aggressive PA, and pasireotide for ACTH-secreting PA. We describe the experience of our multidisciplinary team of endocrinologists, neurosurgeons, neuroradiologists, oncologists, otolaryngologists and pathologists with TMZ and pasireotide treatment for aggressive PAs in terms of their radiological shrinkage and genetic features. We considered five patients with aggressive PA, three of them non-secreting (two ACTH-silent and one becoming ACTH secreting), and two secreting (one GH and one ACTH). TMZ was administrated orally at 150-200 mg/m(2) daily for 5 days every 28 days to all 5 patients, and 2 of them also received pasireotide 600-900 µg bid sc. We assessed the MRI at the baseline and during TMZ or pasireotide treatment. We also checked for MGMT promoter methylation and IDH, BRAF and kRAS mutations. Considering TMZ, two patients showed PA progression, one stable disease and two achieved radiological and clinical response. Pasireotide was effective in reducing hypercortisolism and mass volume, combined with TMZ in one case. Both treatments were generally well tolerated; one patient developed a grade 2 TMZ-induced thrombocytopenia. None of patients developed hypopituitarism while taking TMZ or pasireotide treatment. No genetic anomalies were identified in the adenoma tissue. TMZ and pasireotide may be important therapies for aggressive PA, alone or in combination.

  17. The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamic-pituitary-adrenal axis activity in female rats

    Science.gov (United States)

    Švob Štrac, Dubravka; Muck-Šeler, Dorotea; Pivac, Nela

    2012-01-01

    Aim To elucidate the involvement of noradrenergic system in the mechanism by which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis activity. Methods Plasma corticosterone and adrenocorticotropic hormone (ACTH) levels were determined in female rats treated with diazepam alone, as well as with diazepam in combination with clonidine (α2-adrenoreceptor agonist), yohimbine (α2-adrenoreceptor antagonist), alpha-methyl-p-tyrosine (α-MPT, an inhibitor of catecholamine synthesis), or reserpine (a catecholamine depleting drug) and yohimbine. Results Diazepam administered in a dose of 2.0 mg/kg suppressed basal HPA axis activity, ie, decreased plasma corticosterone and ACTH levels. Pretreatment with clonidine or yohimbine failed to affect basal plasma corticosterone and ACTH concentrations, but abolished diazepam-induced inhibition of the HPA axis activity. Pretreatment with α-MPT, or with a combination of reserpine and yohimbine, increased plasma corticosterone and ACTH levels and prevented diazepam-induced inhibition of the HPA axis activity. Conclusion The results suggest that α2-adrenoreceptors activity, as well as intact presynaptic noradrenergic function, are required for the suppressive effect of diazepam on the HPA axis activity. PMID:22661134

  18. Disease: H00260 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available onodular adrenocortical disease is a form of ACTH-independent adrenal hyperplasia resulting in endogenous Cushing's syndrome. Endocri...ne disease (PPNAD1) PRKAR1A [HSA:5573] [KO:K04739] (PPNAD2) PDE11A [HSA:50940] [KO:

  19. The stress system in depression and neurodegeneration: Focus on the human hypothalamus

    NARCIS (Netherlands)

    Bao, A.-M.; Meynen, G.; Swaab, D.F.

    2008-01-01

    The stress response is mediated by the hypothalamo-pituitary-adrenal (HPA) system. Activity of the corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) forms the basis of the activity of the HPA-axis. The CRH neurons induce adrenocorticotropin (ACTH) releas

  20. Role of Protein Phosphorylation and Tyrosine Phosphatases in the Adrenal Regulation of Steroid Synthesis and Mitochondrial Function.

    Science.gov (United States)

    Paz, Cristina; Cornejo Maciel, Fabiana; Gorostizaga, Alejandra; Castillo, Ana F; Mori Sequeiros García, M Mercedes; Maloberti, Paula M; Orlando, Ulises D; Mele, Pablo G; Poderoso, Cecilia; Podesta, Ernesto J

    2016-01-01

    In adrenocortical cells, adrenocorticotropin (ACTH) promotes the activation of several protein kinases. The action of these kinases is linked to steroid production, mainly through steroidogenic acute regulatory protein (StAR), whose expression and activity are dependent on protein phosphorylation events at genomic and non-genomic levels. Hormone-dependent mitochondrial dynamics and cell proliferation are functions also associated with protein kinases. On the other hand, protein tyrosine dephosphorylation is an additional component of the ACTH signaling pathway, which involves the "classical" protein tyrosine phosphatases (PTPs), such as Src homology domain (SH) 2-containing PTP (SHP2c), and members of the MAP kinase phosphatase (MKP) family, such as MKP-1. PTPs are rapidly activated by posttranslational mechanisms and participate in hormone-stimulated steroid production. In this process, the SHP2 tyrosine phosphatase plays a crucial role in a mechanism that includes an acyl-CoA synthetase-4 (Acsl4), arachidonic acid (AA) release and StAR induction. In contrast, MKPs in steroidogenic cells have a role in the turn-off of the hormonal signal in ERK-dependent processes such as steroid synthesis and, perhaps, cell proliferation. This review analyzes the participation of these tyrosine phosphates in the ACTH signaling pathway and the action of kinases and phosphatases in the regulation of mitochondrial dynamics and steroid production. In addition, the participation of kinases and phosphatases in the signal cascade triggered by different stimuli in other steroidogenic tissues is also compared to adrenocortical cell/ACTH and discussed.

  1. 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.

    Science.gov (United States)

    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...

  2. The effects of moderate-dose steroid therapy in sepsis: A placebo-controlled, randomized study

    Directory of Open Access Journals (Sweden)

    Orhan Yildiz

    2011-01-01

    Conclusions: Moderate-dose steroid therapy has no effect on mortality. Higher basal cortisol and peak cortisol levels were found more reliable mortality indicators compared to RAI. In addition, the study revealed that ACTH level was a significant indicator of mortality.

  3. Cushing Disease After Treatment of Nonfunctional Pituitary Adenoma: A Case Report and Literature Review.

    Science.gov (United States)

    Fang, Hongjuan; Tian, Rui; Wu, Huanwen; Xu, Jian; Fan, Hong; Zhou, Jian; Zhong, Liyong

    2015-12-01

    We describe a very rare case of nonfunctional pituitary adenoma (NFPA) that exhibited corticotrophic activity after resection and radiotherapy. The possible mechanisms of the transformation from NFPA to Cushing disease (CD) are discussed.A 43-year-old man presented with impaired vision, bilateral frontal headaches, and hyposexuality. He had no symptoms suggestive of hypercortisolism, and 8 am plasma cortisol concentration was 67.88 ng/mL. Brain imaging revealed a 15 × 15 × 21-mm sellar mass suggestive of a macroadenoma. The tumor was resected by transsphenoidal surgery and identified by immunohistochemical analysis as a chromophobic adenoma that did not stain for pituitary hormones. The patient was treated with prednisone and levothyroxine replacement therapy. After a third recurrence, the patient presented with clinical features and physical signs of Cushing syndrome. Plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations were elevated, and there was a loss of circadian rhythms. Inferior petrosal sinus sampling after desmopressin showed the central-peripheral ACTH ratio was greater than 3:1. A repeat transsphenoidal resection was undertaken. Immunohistochemistry revealed ACTH positivity. Three months following surgery, imaging showed little residual tumor, but plasma ACTH remained elevated. He was referred for postoperative Gamma Knife radiotherapy.The immunological activity and biological features of the hormones secreted from a pituitary adenoma vary with time. Because long-term outcomes are unpredictable, postoperative follow-up is essential to detect postoperative transformation from NFPA to CD.

  4. A Fall in Plasma Free Fatty Acid (FFA) Level Activates the Hypothalamic-Pituitary-Adrenal Axis Independent of Plasma Glucose: Evidence for Brain Sensing of Circulating FFA

    Science.gov (United States)

    Oh, Young Taek; Oh, Ki-Sook; Kang, Insug

    2012-01-01

    The brain responds to a fall in blood glucose by activating neuroendocrine mechanisms for its restoration. It is unclear whether the brain also responds to a fall in plasma free fatty acids (FFA) to activate mechanisms for its restoration. We examined whether lowering plasma FFA increases plasma corticosterone or catecholamine levels and, if so, whether the brain is involved in these responses. Plasma FFA levels were lowered in rats with three independent antilipolytic agents: nicotinic acid (NA), insulin, and the A1 adenosine receptor agonist SDZ WAG 994 with plasma glucose clamped at basal levels. Lowering plasma FFA with these agents all increased plasma corticosterone, but not catecholamine, within 1 h, accompanied by increases in plasma ACTH. These increases in ACTH or corticosterone were abolished when falls in plasma FFA were prevented by Intralipid during NA or insulin infusion. In addition, the NA-induced increases in plasma ACTH were completely prevented by administration of SSR149415, an arginine vasopressin receptor antagonist, demonstrating that the hypothalamus is involved in these responses. Taken together, the present data suggest that the brain may sense a fall in plasma FFA levels and activate the hypothalamic-pituitary-adrenal axis to increase plasma ACTH and corticosterone, which would help restore FFA levels. Thus, the brain may be involved in the sensing and control of circulating FFA levels. PMID:22669895

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

    Science.gov (United States)

    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.

  6. Sodium oxybate increases prolactin secretion in narcolepsy patients and healthy controls

    NARCIS (Netherlands)

    Donjacour, C.E.; Aziz, N.A.; Frolich, M.; Roelfsema, F.; Overeem, S.; Lammers, G.J.; Pijl, H.

    2011-01-01

    OBJECTIVE: Hypocretin deficiency causes narcolepsy and may affect neuroendocrine systems, including TSH, ACTH and LH secretion. Symptoms can be treated effectively with sodium oxybate (SXB) in many patients. This study was performed to compare prolactin (PRL) secretion in patients and matched contro

  7. Comorbidities in Cushing’s disease

    NARCIS (Netherlands)

    S.T. Sharma; L.K. Nieman; R.A. Feelders (Richard)

    2015-01-01

    textabstractIntroduction: Cushing’s disease is a rare disorder characterized by overproduction of ACTH from a pituitary adenoma leading to hypercortisolemia that in turn leads to increased morbidity and mortality.Methods: Here we review the comorbidities associated with Cushing’s disease and their i

  8. Resveratrol inhibits steroidogenesis in human fetal adrenocortical cells at the end of first trimester

    DEFF Research Database (Denmark)

    Savchuk, Iuliia; Morvan, Marie-Line; Søeborg, Tue

    2017-01-01

    steroidogenesis at gestational weeks (GW) 9-12. METHODS AND RESULTS: Adrenals from aborted fetuses (GW10-12) were used to prepare primary cultures of human fetal adrenocortical cells (HFAC). HFAC were treated in the presence or absence of ACTH (10 ng/ml) with or without resveratrol (10 μM) for 24 hours...

  9. Disease: H00033 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available se which reduces the 5 year survival rate to less than 10%. Oncogenes and tumor-suppressor genes involved in adrenal carcinomas...ptor gene have recently been found in undifferentiated adenomas and in aggressive ACCs. Cancer ACTH-R (delet

  10. Cortisol secretion in patients with normoprolactinemic amenorrhea

    DEFF Research Database (Denmark)

    Boesgaard, S; Hagen, C; Andersen, A N;

    1988-01-01

    Patients with functional amenorrhea have raised central dopaminergic activity and opioid-mediated GnRH inhibition leading to inhibition of hypothalamic-pituitary-ovarian function. In the present study, basal serum cortisol and ACTH levels were measured in normoprolactinemic amenorrheic patients...

  11. Grooming behavior of spontaneously hypertensive rats

    NARCIS (Netherlands)

    Buuse, M. van den; Jong, Wybren de

    1987-01-01

    In an open field spontaneously hypertensive rats (SHR) exhibited lower scores for grooming when compared to their normotensive controls, the Wistar Kyoto rats (WKY). After i.c.v. injection of 1 μg ACTH1–24 cumulative 50-min grooming scores were lower in SHR. Analysis of subscores indicated that the

  12. OmniGen-AF alters rectal temperature (RT) and leukocyte profiles in dairy cows exposed to heat stress (HS) following acute activation of the stress axis

    Science.gov (United States)

    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)...

  13. Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency

    DEFF Research Database (Denmark)

    Jackson, Robert S; Creemers, John W M; Farooqi, I Sadaf

    2003-01-01

    , some mature ACTH and glucagon-like peptide 17-36(amide) were detectable in her plasma, suggesting that the production of these hormones, at least in humans, does not have an absolute dependence on PC1. The presence of severe obesity and the absence of growth retardation in both subjects contrast...

  14. Theory-Driven Models for Correcting Fight or Flight Imbalance in Gulf War Illness

    Science.gov (United States)

    2013-09-01

    feedback during the nocturnal period when compared with control subjects and CFS 74 subjects comorbid with fibromyalgia (FM) [14, 15]. Conversely...pulsatile ACTH and cortisol secretion in patients with fibromyalgia and/or 648 chronic fatigue syndrome. Brain Behav Immun 18: 314–325. 649 15

  15. Treatment of myoclonic encephalopathy of childhood (Kinsbourne sydrome with methotrexate and intravenous

    Directory of Open Access Journals (Sweden)

    Torres Mayagoita Dessiré

    2014-07-01

    Full Text Available Myoclonic encephalopathy of infancy is an important model of natural tumor regression. Patients with opsoclonus-myoclonus generate an immune response against a variety of brain antigens. It is probable that neuroblastoma (or viral antigens and the cer- ebelum are joint targets of an immunologic attack. Most cases show a remarkable reponse to ACTH, intravenous gammaglobulin and rituximab.

  16. Behavioural actions of vasoactive intestinal peptide (VIP)

    NARCIS (Netherlands)

    Kloet, E.R.; Cottrell, G.A.; Veldhuis, H.D.; Rostene, W.H.

    1984-01-01

    The effect of vasoactive intestinal peptide (VIP) was studied on fear-motivated behaviours, exploration of a novel environment and on novelty and ACTH-induced grooming. VIP was administered via a plastic cannula into the lateral ventricle. Retention of a step-through passive avoidance task was inhib

  17. Circadian regulation of cortisol release in behaviorally split golden hamsters.

    Science.gov (United States)

    Lilley, Travis R; Wotus, Cheryl; Taylor, Daniel; Lee, Jennifer M; de la Iglesia, Horacio O

    2012-02-01

    The master circadian clock located within the hypothalamic suprachiasmatic nucleus (SCN) is necessary for the circadian rhythm of glucocorticoid (GC) release. The pathways by which the SCN sustains rhythmic GC release remain unclear. We studied the circadian regulation of cortisol release in the behaviorally split golden hamster, in which the single bout of circadian locomotor activity splits into two bouts approximately 12 h apart after exposing the animals to constant light conditions. We show that unsplit control hamsters present a single peak of cortisol release that is concomitant with a single peak of ACTH release. In contrast, split hamsters show two peaks of cortisol release that are approximately 12 h appart and are appropriately phased to each locomotor activity bout but surprisingly do not rely on rhythmic release of ACTH. Our results are consistent with a model in which the circadian pacemaker within the SCN regulates the circadian release of GC via input to the hypothalamo-pituitary-adrenal axis and via a second regulatory pathway, which likely involves sympathetic innervation of the adrenal and can operate even in the absence of ACTH circadian rhythmic release. Furthermore, we show that although the overall 24-h cortisol output in split hamsters is lower than in unsplit controls, split hamsters release constant low levels of ACTH. This result suggests that the timing, rather than the absolute amount, of cortisol release is more critical for the induction of negative feedback effects that regulate the hypothalamo-pituitary-adrenal axis.

  18. Reversible hyporeninemic hypoaldosteronism in a patient with tetraplegia.

    Science.gov (United States)

    Inaba, M; Katayama, S; Omoto, A; Maruno, Y; Itabashi, A; Ishii, J; Morimoto, S

    1989-02-01

    A 66-year-old man with tetraplegia developed hyperkalemia. Hyporeninemic hypoaldosteronism was disclosed on the basis of a lack of response of plasma renin activity to furosemide administration or tilting with marked hypotension and a subnormal response of aldosterone to furosemide stimulation, tilting, angiotensin II infusion and ACTH administration, as well as increased vascular responsiveness to angiotensin II infusion. Of interest was the finding that urinary excretion of epinephrine and norepinephrine was markedly reduced, indicating that hyporeninemia may possibly be due to a chronic lack of sympathetic nervous stimuli. The patient was treated with sodium polystyrene sulfonate resin and/or 9-alpha-fluorohydrocortisone, and wheelchair rehabilitation. However, even after stopping 8-month-mineralcorticoid replacement, normokalemia was maintained. Reexamination of the renin-angiotensin-aldosterone system revealed a normalized response to tilting or ACTH administration along with the normal catecholamine excretion. One more point to be noted is that ACTH administration resulted in a rise in the plasma levels of cortisol, corticosterone and 18-OH-corticosterone, but not aldosterone. This may be attributed to ACTH-stimulated 18-OH-corticosterone derived from the zona fasciculata or alternatively to a partial defect of corticosterone methyl oxidase type II (18-dehydrogenase) in the adrenal glomerulosa cells. These results suggested that hyporeninemic hypoaldosteronism may have been attributable to a decrease in systemic nervous stimuli and that such abnormalities were reversible.

  19. Hipofunción glucocorticoide en la distrofia miotónica

    Directory of Open Access Journals (Sweden)

    L. Forga

    Full Text Available Introducción. La distrofia miotónica (DM1 es una enfermedad autonómica dominante cuyo defecto genético consiste en una expansión por repeticiones del triplete CTG en un gen que codifica una proteín-kinasa serina-treonina AMPc dependiente llamada DMPK. Se trata de una enfermedad multisistémica con conocida repercusión endocrinológica. En cuanto a la función suprarrenal, los resultados descritos han sido variables aunque últimamente se interpretan como indicadores de una hiperactividad del eje hipotálamo-hipófiso-adrenal. Material y métodos. Se han estudiado 25 pacientes (13 hombres y 12 mujeres afectos de DM1 a los que se ha analizado: cortisol y ACTH basales, test de estímulo con 0,25 mg de ACTH para cortisol y test de CRH para cortisol y ACTH. Asimismo se valoró el grado de expansión de CTG por Southern blot y PCR. Como grupo control para basales se estudiaron 25 individuos sanos equiparables por edad y sexo, a 11 de los cuales se realizó test de CRH. Resultado. Se diagnosticó a un paciente de insuficiencia suprarrenal primaria no autoinmune. En el resto de casos no hubo diferencias entre la ACTH basal de pacientes y controles, y la respuesta de cortisol a ACTH fue normal. Los pacientes presentaron un nivel de cortisol basal más bajo (p<0,01 y también mostraron, tras estímulo con CRH, una menor respuesta de cortisol (p<0,05 con cifras medias de ACTH más elevadas. Conclusiones. Nuestros datos difieren de las últimas publicaciones y apuntan a una hipofunción suprarrenal por falta de eficacia de la ACTH sobre su receptor o a nivel post-receptor. Sugerimos que la etiología puede estar relacionada con el defecto subyacente en el gen que codifica la DMPK.

  20. 促肾上腺皮质激素治疗肾性蛋白尿的研究%Role of adrenocorticotropin therapy in proteinuric nephropathies

    Institute of Scientific and Technical Information of China (English)

    鲍浩; 龚如军

    2011-01-01

    Despite the advances in immunosuppression and blockade of the renin-angiotensin-aldosterone cascade, the refractory nephrotic syndrome remains to be a therapeutic challenge. Adrenocorticotropin (ACTH), a pituitary neuroimmunoendocine pelypeptide, was widely used about half century ago as an effective therapy for childhood nephrotic syndrome but has since largely been replaced by less costly, orally administered synthetic glucocorticoids. In addition to controlling steroidogenesis as a component of the hypothalamic-pituitary-adrenal axis, ACTH also acts as an important physiological agonist of the melanocortin system. Lately, accumulating clinical and experimental evidence suggests that ACTH possesses anti-proteinuric, lipid lowering and reno-protective activities. ACTH therapy is prominently effective in inducing remission of nephrotic syndrome in patients with a variety of proteinuric nephropathies, even those resistant to steroids and other immunosuppressants. This review describes the biology and physiology of ACTH, with particular emphasis on melanocortin effects. Findings from the latest clinical trials are also discussed with perspectives on potential applications of ACTH as a treatment for nephrotic glomerulopathies.%促肾上腺皮质激素(ACTH)是脑垂体前叶分泌的神经内分泌多肽.它是体内下丘脑一垂体一肾上腺轴和黑素皮质素系统的重要组成部分.ACTH具有促进肾上腺皮质激素分泌和皮质增生、降低血脂、刺激胰岛素分泌、调节免疫和神经系统功能等作用,曾被广泛用于治疗小儿肾病综合征(NS).近来越来越多的临床证据显示,ACTH能够有效缓解难治性NS患者蛋白尿,但迄今大多是单中心非随机临床研究.ACTH疗效可能与其促进糖皮质激素分泌、降低血脂、调节免疫、保护足细胞以及调节胆碱能抗炎通路有关,但迄今尚不明确;需要综合多种研究手段进一步研究阐述.

  1. Chronic orthostatic and antiorthostatic restraint induce neuroendocrine, immune and neurophysiological disorders in rats

    Science.gov (United States)

    Assenmacher, I.; Mekaouche, M.; Maurel, D.; Barbanel, G.; Givalois, L.; Boissin, J.; Malaval, F.; Ixart, G.

    The tail-cast suspension rat model has been developed in ground laboratories interested in space physiology for extensive study of mechanisms causing the pathophysiological syndrome associated with space flights. We used individually-caged male rats to explore the effects of acute and chronic (7d) orthostatic restraint (OR) and head-down anti-orthostatic restraint (AOR) on a series of physiological variables. The acute restraint study showed that (1) the installation of the OR device induced an acute reaction for 2 days, with a substantial rise in ACTH (x2) and CORT (x6), and that (2) the head-down tilt from OR to AOR induced (i) within 10 min and lasting 60 min a 2-fold rise in the intra-cerebro-ventricular pressure (Picv) monitored with an icv telemetric recording system, which receded to normal between 60 and 120 min; and (ii) within 30 min a short-lived 4-fold rise in plasma ACTH and CORT levels. Chronic OR induced (1) the suppression of the diurnal ACTH/CORT rhythm, with increased mean levels, especially for ACTH, (2) a degraded circadian locomotor activity rhythm manifested by a significant reduction in the spectral power of the 24h periodicity and a concomitant emergence of shorter (ultradian) periodicities, (3) an associated, but less pronounced alteration of the diurnal rhythm in body temperature; and (4) a marked increase in baseline plasma levels of IL-1β and an increased reactivity in cytokine release following an E. coli endotoxin (LPS) challenge. AOR induced (1) a similar obliteration of the circadian ACTH/CORT rhythm, (2) the loss of close correlation between ACTH and CORT, (3) a generalized increase in baseline plasma IL-1β levels and (4) more extensive degradation of the arcadian periodicity for both locomotor activity and, to a lesser extent, body temperature, replaced by dominant spectral powers for ultradian periodicities (3 to 10h). In conclusion, both experimental paradigms — but AOR more than OR — caused a blockade of the arcadian

  2. Self-suppression of corticosteroidogenesis: evidence for a role of adrenal 5 alpha-reductase.

    Science.gov (United States)

    Carsia, R V; Scanes, C G; Malamed, S

    1984-12-01

    Exogenous corticosterone (B), the natural glucocorticoid product of rats, suppressed endogenous B production of isolated rat adrenocortical cells induced by alpha ACTH-(1-24), [9-tryptophan (O-nitrophenylsulfenyl)]ACTH-(1-24) [( Trp (Nps)9]ACTH-(1-24], and cAMP as well as pregnenolone supported-steroidogenesis. This self-suppression occurred within 2 h. It was dependent on the concentration of exogenous B. However, self-suppression did not alter the half-maximal steroidogenic concentration (ED50) of each steroidogenic agent. In addition, exogenous B did not suppress ACTH-induced cAMP production or gross protein synthesis, as measured by leucine incorporation into bulk cellular proteins. These results with isolated cells suggested at least two mechanisms for self-suppression: 1) exogenous B inhibited steroidogenic steps in a noncompetitive manner, and/or 2) exogenous B induced B degradation. In this study we examined the effect of exogenous B on the degradation of B. Accordingly, we measured the adrenal 5 alpha-reductase activity (5 alpha RA) of cell homogenates prepared from treated cells. Isolated adrenocortical cells were incubated for 2 h with alpha ACTH-(1-24), ovine PRL (oPRL), and B. They were then homogenized and assayed for 5 alpha RA, as indicated by the disappearance of exogenous B, as shown by RIA. In addition, the percentage of exogenous tritium-labeled B [( 3H]B) converted to 5 alpha-dihydrocorticosterone (DHB), the principal reduced metabolite of B, was determined by TLC. Isolated adrenocortical cells from intact rats showed insignificant 5 alpha RA and DHB formation when incubated with or without alpha ACTH-(1-24) and with or without oPRL. However, with exogenous B, there was significant 5 alpha RA and DHB formation. oPRL plus B decreased DHB formation. The effects of B and oPRL were more demonstrable with cells from hypophysectomized rats. These cells exhibited high 5 alpha RA and DHB formation; exogenous B increased these values, whereas o

  3. Cortisol response to low dose versus standard dose (back-to-back adrenocorticotrophic stimulation tests in children and young adults with thalassemia major

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    Ashraf T Soliman

    2013-01-01

    Full Text Available Background: Thalassemia major patients with repeated blood transfusion have high prevalence of endocrinopathies due to iron overload. Materials and Methods: We examined the adrenocortical function in 23 thalassemic patients (10 children and 13 young adults aged 8-26 years. Serum cortisol and dehydroepiandrosterone sulfate (DHEA-S concentrations were determined in each subject before blood transfusion both in basal condition and after low dose (LD (1 μg, followed by standard dose (SD (250 μg, respectively with synthetic corticotrophin beta 1-24 ACTH (Synacthen, Ciba. Normal controls were a group of 13 age- and sex-matched normal subjects. Results: Using a peak total cortisol cutoff level of 550 nmol/L and increments of 200 μg above basal cortisol, adrenal insufficiency (AI was demonstrated in 8 patients (34.7% after the LD ACTH and in 2 patients (8.7% after SD cosyntropin (ACTH test, but none of the controls. Using a peak total cortisol cutoff level of 420 nmol/L and increments of 200 μg above basal cortisol, AI was demonstrated in 5 patients (21.7% after the LD ACTH and in 2 patients after SD ACTH test (8.7%, but none of controls. All patients with biochemical AI were asymptomatic with normal serum sodium and potassium concentrations and had no history suggestive of adrenal pathology. The peak cortisol concentrations in thalassemic patients with impaired adrenal function both after 1 μg and 250 μg cosyntropin (294 ± 51 nmol/L and 307 ± 58.6 were significantly lower than those with patients with normal (454 ± 79.7 nmol/L and 546.1 ± 92.2 nmol/L, respectively and controls (460.2 ± 133.4 nmol/L and 554.3 ± 165.8 nmol/L, respectively. Adolescents and young adults, but not children with thalassaemia, had significantly lower peak cortisol concentration after SD ACTH versus controls. Peak cortisol response to LD ACTH was correlated significantly with peak cortisol response to SD in all patients (r = 0.83, P < 0.0001. In adolescents and

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

    Science.gov (United States)

    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

  5. Characterization of melanocortin receptors from stingray Dasyatis akajei, a cartilaginous fish.

    Science.gov (United States)

    Takahashi, Akiyoshi; Davis, Perry; Reinick, Christina; Mizusawa, Kanta; Sakamoto, Tatsuya; Dores, Robert M

    2016-06-01

    Melanocortin (MC) systems are composed of MC peptides such as adrenocorticotropic hormone (ACTH), several molecular forms of melanocyte-stimulating hormones (MSHs) and MC receptors (MCRs). Here we demonstrated that the cartilaginous fish, Dasyatis akajei (stingray) expresses five subtypes of MCR genes-mc1r to mc5r-as in the case of teleost and tetrapod species. This is the first evidence showing the presence of the full repertoire of melanocortin receptors in a single of cartilaginous fish. Expression of respective stingray mcr cDNAs in Chinese hamster ovary cells revealed that Des-acetyl-α-MSH exhibited cAMP-producing activity indistinguishable to ACTH(1-24) on MC1R and MC2R, while the activity of Des-acetyl-α-MSH on MC3R, MC4R, and MC5R were similar to or slightly greater than that of ACTH(1-24). Notably, in contrast to the other vertebrates, MC2R did not require coexpression with a melanocortin receptor-2 accessory protein 1 (mrap1) cDNA for functional expression. One of the roles of MC system resides in regulation of the pituitary-interrenal (PI) axis-a homologue of tetrapod pituitary-adrenal axis. In stingray, interrenal tissues were shown to express mc2r and mc5r as major MCR genes. These results established the presence of functional PI axis in stingray at the level of receptor molecule. While MC2R participates in adrenal functions together with MRAP1 in tetrapod species, the fact that sensitivity of MC5R to Des-acetyl-α-MSH and ACTH(1-24) were two order of magnitude higher than MC2R without coexpression with MRAP1 suggested that MC5R could play a more important role than MC2R to transmit signals conveyed by ACTH and MSHs if MRAP1 is really absent in the stingray.

  6. Cushing’s Syndrome in Multiple Endocrine Neoplasia Type 1

    Science.gov (United States)

    Simonds, William F.; Varghese, Sarah; Marx, Stephen J.; Nieman, Lynnette K.

    2011-01-01

    Summary Objective In patients with multiple endocrine neoplasia type 1 (MEN1), Cushing’s syndrome (CS) from endogenous hypercortisolism can result from pituitary, adrenal, or other endocrine tumors. The purpose of this study was to characterize the range of presentations of CS in a large series of MEN1 patients. Design Retrospective review of NIH Clinical Center inpatient records over an approximately 40 year period. Patients 19 patients (8 males, 11 females) with CS and MEN1. Measurements Biochemical, imaging, surgical, and pathological findings. Results An etiology was determined for 14 of the 19 patients with CS and MEN1: 11 (79%) had Cushing’s disease (CD) and three (21%) had ACTH-independent CS due to adrenal tumors, frequencies indistinguishable from sporadic CS. Three of 11 MEN1 patients with CD (27%) had additional non-ACTH secreting pituitary microadenomas identified at surgery, an incidence 10-fold higher than in sporadic CD. Ninety-one percent of MEN1 patients with CD were cured after surgery. Two of three MEN1 patients with ACTH-independent CS (67%) had adrenocortical carcinoma. One patient with adrenal cancer and another with adrenal adenoma were cured by unilateral adrenalectomy. No case of ectopic ACTH secretion was identified in our patient cohort. The etiology of CS could not be defined in five patients; in three of these, hypercortisolism appeared to resolve spontaneously. Conclusions The tumor multiplicity of MEN1 can be reflected in the anterior pituitary, MEN1-associated ACTH-independent CS may be associated with aggressive adrenocortical disease, and an etiology for CS in MEN1 may be elusive in a substantial minority of patients. PMID:21916912

  7. Stress-related gene expression in brain and adrenal gland of porcine fetuses and neonates.

    Science.gov (United States)

    Schwerin, Manfred; Kanitz, Ellen; Tuchscherer, Margret; Brüssow, Klaus-Peter; Nürnberg, Gerd; Otten, Winfried

    2005-03-01

    This study was conducted to examine stress-induced effects on gene expression of specific markers for HPA axis and neuronal activity in fetuses and neonatal pigs. Brain, pituitary gland, and adrenal gland were obtained to determine the mRNA levels for corticotropin-releasing hormone (CRH), CRH receptor 1 (CRHR1), pro-opiomelanocortin (POMC), ACTH receptor (MC2R), c-jun and c-fos. The suitability of these molecular markers was determined in neonatal pigs which were maternally deprived for two hours. It was found that maternal deprivation caused significantly higher transcript levels of c-fos and CRH in brain accompanied by a down-regulation of CRHR1 mRNA and an up-regulation of c-jun in the pituitary gland. To determine the effect of elevated maternal cortisol levels on gene expression of these molecular markers in fetuses, pregnant sows were treated with 100 IU ACTH (Synacthen Depot) s.c. every two days between Day 49 and Day 75 of gestation (normal gestation length 114 days). Animals were killed 48 hours after the last ACTH administration and fetuses of each sow were isolated. The ACTH treatment of sows significantly increased mRNA expression of c-fos but not of CRH in the fetal brain, and significantly decreased MC2R mRNA expression in the adrenal gland. However, HPA axis seems not to be fully developed in Day 77-fetuses because fetal pituitary CRHR1 and POMC mRNA expression was low in most of the fetuses. Although the expression of endocrine regulatory factors was partially incomplete in fetuses at the beginning of the third-trimester, ACTH dependent activation of c-fos mRNA in brain indicates a stress-related increase of neuronal activity. Based on these results it is assumed that prenatal stress in pigs may also have effects on the activity of the HPA axis in the offspring.

  8. HPA axis dysregulation in men with hypersexual disorder.

    Science.gov (United States)

    Chatzittofis, Andreas; Arver, Stefan; Öberg, Katarina; Hallberg, Jonas; Nordström, Peter; Jokinen, Jussi

    2016-01-01

    Hypersexual disorder integrating pathophysiological aspects such as sexual desire deregulation, sexual addiction, impulsivity and compulsivity was suggested as a diagnosis for the DSM-5. However, little is known about the neurobiology behind this disorder. A dysregulation of the hypothalamic pituitary adrenal (HPA) axis has been shown in psychiatric disorders but has not been investigated in hypersexual disorder. The aim of this study was to investigate the function of the HPA axis in hypersexual disorder. The study includes 67 male patients with hypersexual disorder and 39 healthy male volunteers. Basal morning plasma levels of cortisol and ACTH were assessed and low dose (0.5mg) dexamethasone suppression test was performed with cortisol and ACTH measured post dexamethasone administration. Non-suppression status was defined with DST-cortisol levels ≥ 138 nmol/l. The Sexual Compulsive scale (SCS), Hypersexual disorder current assessment scale (HD:CAS), Montgomery-Åsberg Depression Scale-self rating (MADRS-S) and Childhood trauma questionnaire (CTQ), were used for assessing hypersexual behavior, depression severity and early life adversity. Patients with hypersexual disorder were significantly more often DST non-suppressors and had significantly higher DST-ACTH levels compared to healthy volunteers. The patients reported significantly more childhood trauma and depression symptoms compared to healthy volunteers. CTQ scores showed a significant negative correlation with DST-ACTH whereas SCS and HD:CAS scores showed a negative correlation with baseline cortisol in patients. The diagnosis of hypersexual disorder was significantly associated DST non-suppression and higher plasma DST-ACTH even when adjusted for childhood trauma. The results suggest HPA axis dysregulation in male patients with hypersexual disorder.

  9. Cortistatin Is a Key Factor Regulating the Sex-Dependent Response of the GH and Stress Axes to Fasting in Mice.

    Science.gov (United States)

    Cordoba-Chacón, José; Gahete, Manuel D; Pozo-Salas, Ana I; de Lecea, Luis; Castaño, Justo P; Luque, Raúl M

    2016-07-01

    Cortistatin (CORT) shares high structural and functional similarities with somatostatin (SST) but displays unique sex-dependent pituitary actions. Indeed, although female CORT-knockout (CORT-KO) mice exhibit enhanced GH expression/secretion, Proopiomelanocortin expression, and circulating ACTH/corticosterone/ghrelin levels, male CORT-KO mice only display increased plasma GH/corticosterone levels. Changes in peripheral ghrelin and SST (rather than hypothalamic levels) seem to regulate GH/ACTH axes in CORT-KOs under fed conditions. Because changes in GH/ACTH axes during fasting provide important adaptive mechanisms, we sought to determine whether CORT absence influences GH/ACTH axes during fasting. Accordingly, fed and fasted male/female CORT-KO were compared with littermate controls. Fasting increased circulating GH levels in male/female controls but not in CORT-KO, suggesting that CORT can be a relevant regulator of GH secretion during fasting. However, GH levels were already higher in CORT-KO than in controls in fed state, which might preclude a further elevation in GH levels. Interestingly, although fasting-induced pituitary GH expression was elevated in both male/female controls, GH expression only increased in fasted female CORT-KOs, likely owing to specific changes observed in key factors controlling somatotrope responsiveness (ie, circulating ghrelin and IGF-1, and pituitary GHRH and ghrelin receptor expression). Fasting increased corticosterone levels in control and, most prominently, in CORT-KO mice, which might be associated with a desensitization to SST signaling and to an augmentation in CRH and ghrelin-signaling regulating corticotrope function. Altogether, these results provide compelling evidence that CORT plays a key, sex-dependent role in the regulation of the GH/ACTH axes in response to fasting.

  10. Analysis of the pharmacological properties of chicken melanocortin-2 receptor (cMC2R) and chicken melanocortin-2 accessory protein 1 (cMRAP1).

    Science.gov (United States)

    Barlock, Travis K; Gehr, Deshae T; Dores, Robert M

    2014-09-01

    The chicken (Gallus gallus) melanocortin-2 receptor (cMC2R) can be functionally expressed in CHO cells when chicken melanocortin-2 receptor accessory protein 1 (cMRAP1) is co-expressed. The transiently transfected CHO cells responded in a robust manner to stimulation by hACTH(1-24) (EC50 value=2.7 × 10(-12)M +/- 1.3 × 10(-12)), but the transfected CHO cells could not be stimulated by NDP-MSH at concentrations as high as 10(-7)M. Incubation of cMC2R/cMRAP1 transfected cells with alanine substituted analogs of hACTH(1-24) at amino acid positions F(7) or W(9) completely blocked stimulation of the transfected cells. Similarly, incubation of cMC2R/cMRAP1 transfected cells with an analog of hACTH(1-24) with alanine substitutions at amino acid positions R(17)R(18)P(19) resulted in a 276 fold shift in EC50 value relative to the positive control (pHFRW motif and KKRRP motif of hACTH(1-24), and both motifs are required for full activation of the receptor. While previous studies had shown that Anolis carolinensis MC2R and Xenopus tropicalis MC2R could be functionally expressed in CHO cells that co-expressed mouse MRAP1, co-expression of these non-mammalian tetrapod MC2Rs with cMRAP1 resulted in a significant increase in sensitivity to hACTH(1-24), as measured by EC50 value, for A. carolinensis MC2R (p<0.005) and X. tropicalis MC2R (p<0.007). The implications of these observations are discussed.

  11. 60 YEARS OF POMC: Melanocortin receptors: evolution of ligand selectivity for melanocortin peptides.

    Science.gov (United States)

    Dores, Robert M; Liang, Liang; Davis, Perry; Thomas, Alexa L; Petko, Bogdana

    2016-05-01

    The evolution of the melanocortin receptors (MCRs) is linked to the evolution of adrenocorticotrophic hormone (ACTH), the melanocyte-stimulating hormones (MSHs), and their common precursor pro-opiomelanocortin (POMC). The origin of the MCRs and POMC appears to be grounded in the early radiation of the ancestral protochordates. During the genome duplications that have occurred during the evolution of the chordates, the organization plan for POMC was established, and features that have been retained include, the high conservation of the amino acid sequences of α-MSH and ACTH, and the presence of the HFRW MCR activation motif in all of the melanocortin peptides (i.e. ACTH, α-MSH, β-MSH, γ-MSH, and δ-MSH). For the MCRs, the chordate genome duplication events resulted in the proliferation of paralogous receptor genes, and a divergence in ligand selectivity. While most gnathostome MCRs can be activated by either ACTH or the MSHs, teleost and tetrapod MC2R orthologs can only be activated by ACTH. The appearance of the accessory protein, MRAP1, paralleled the emergence of teleost and tetrapods MC2R ligand selectivity, and the dependence of these orthologs on MRAP1 for trafficking to the plasma membrane. The accessory protein, MRAP2, does not affect MC2R ligand selectivity, but does influence the functionality of MC4R orthologs. In this regard, the roles that these accessory proteins may play in the physiology of the five MCRs (i.e. MC1R, MC2R, MC3R, MC4R, and MC5R) are discussed.

  12. Pituitary-adrenocortical adjustments to transport stress in horses with previous different handling and transport conditions

    Directory of Open Access Journals (Sweden)

    E. Fazio

    2016-08-01

    Full Text Available Aim: The changes of the hypothalamic pituitary adrenal (HPA axis response to a long distance transportation results in increase of adrenocorticotropic hormone (ACTH and cortisol levels. The purpose of the study was to quantify the level of short-term road transport stress on circulating ACTH and cortisol concentrations, related to the effect of previous handling and transport experience of horses. Materials and Methods: The study was performed on 56 healthy horses after short-term road transport of 30 km. The horses were divided into four groups, Groups A, B, C, and D, with respect to the handling quality: Good (Groups A and B, bad (Group D, and minimal handling (Group C conditions. According to the previous transport, experience horses were divided as follows: Horses of Groups A and D had been experienced long-distance transportation before; horses of Groups B and C had been limited experience of transportation. Results: One-way RM-ANOVA showed significant effects of transport on ACTH changes in Groups B and C and on cortisol changes in both Groups A and B. Groups A and B showed lower baseline ACTH and cortisol values than Groups C and D; Groups A and B showed lower post-transport ACTH values than Groups C and D. Groups A, B, and C showed lower post-transport cortisol values than Group D. Only Groups A and B horses have shown an adequate capacity of stress response to transportation. Conclusion: The previous transport experience and quality of handling could influence the HPA axis physiological responses of horses after short-term road transport.

  13. Inferior petrosal sinus sampling in the diagnosis of adrenocorticotropin dependent Cushing syndrome with unknown orign%促肾上腺皮质激素依赖性库欣综合征患者岩下窦静脉采血的临床应用探讨

    Institute of Scientific and Technical Information of China (English)

    沈雪峰; 袁德全; 岳明; 冯娟娟

    2011-01-01

    Objective To evaluate the value of inferior petrosal sinus sampling (IPSS) in the diagnosis of adreno-corticotropic hormone ( ACTH ) dependent Cushing syndrome ( CS ) with unknown origin. Methods IPSS was carried out for the diagnosis of 16 cases with ACTH dependent CS who had not been identified after a series of dexamethasone suppression tests and radiological examinations. The ratio of inferior petrosal sinus/peripheral ACTH was assayed. The sensitivity and specificity of diagnosis of the Cushing disease were estimated. Results The inferior petrosal sinus/peripheral ACTH ratio was over 2. 0 in 13 cases. Twelve cases underwent surgery with pathological diagnosis of pituitary ACTH adenoma, 1 patient relieved after γ knife treatment. The ratio was < 2.0 in 3 cases including 2 pulmonary carcinoid and one pituitary ACTH adenoma. The sensitivity and specify of IPSS for the diagnosis of Cushing disease were 13/14and 2/2 respectively. Conclusion IPSS was a safe technique with high sensitivity, specify and infrequent complications in the diagnosis of ACTH dependent Cushing disease. It had great clinical value in the differential diagnosis of ACTH dependent Cushing disease with unknown origin.%目的 研究并探讨岩下窦静脉采血(IPSS)在疑难库欣综合征(CS)诊断中的应用价值。方法 16例疑难CS患者行双侧岩下窦和外周静脉采血,测定岩下窦与外周静脉血促肾上腺皮质激素(ACTH)浓度比,评价IPSS对库欣病诊断的敏感度和特异度。结果 13例患者岩下窦与外周静脉血ACTH的比值>2.0,其中12例经蝶窦垂体手术治疗,病理证实为垂体ACTH腺瘤;1例行鞍区γ-刀治疗,治疗后患者症状好转。3例岩下窦与外周静脉血ACTH的比值<2.0,其中2例为右肺类癌,另1例为垂体ACTH腺瘤。IPSS诊断库欣病的敏感度和特异度分别为13/14和2/2。结论 IPSS诊断疑难库欣病的敏感度和特异度均较高,且操作安全,并发症少,可作为

  14. Evaluation of stress hormones in traumatic brain injury patients with gastrointestinal bleeding

    Institute of Scientific and Technical Information of China (English)

    Biteghe-Bi-Nzeng Alain-Pascal; WEI Hui-jie; CHEN Xin; ZHANG Jian-ning

    2010-01-01

    Objective:To evaluate the local risk factors of traumatic brain injury(TBI)patients developing gastrointestinal(GI)bleeding during the early hospitalization in neurosurgery intensive care unit(NICU).Method:From September 2005 to February 2006,41 patients admitted to NICU and 13 healthy volunteers were involved in our study.Blood samples at 24 hours,2-3 days and 5-7 days were obtained from each patient via arterial line at 8 a.m.to measure the concentrations of serum adrenocorticotropic hormone(ACTH),total cortisol and gastrin.The collected serum was immersed in an ice bath and tested by the Immulite 1000 systems.Data were analyzed by SPSS 11.5.Results:Within 24 hours following TBI,the concentrations of total cortisol,ACTH and gastrin increased proportionally to the severity of injury,especially significant in the experimental group(P<0.05).The concentrations of ACTH and gastrin were higher in the GI bleeding positive group than in the GI bleeding negative group,(F=1.413,P=0.253)for ACTH and(F=9.371,P=0.006)for gastrin.GI bleeding had a positive correlation with gastrin concentration(r=0.312,P<0.05)and a negative correlation with serum hemoglobin(Hb)(r=-0.420,P<0.01).The clinical incidence of GI bleeding was 24.39%(10/41)in the experimental group.Within 24 hours,GI bleeding had a strong correlation with gastrin concentration(OR=26.643,P<0.05)and hematocrit(Hct)(OR=5.385,P<0.05).High ACTH concentration(>100 pg/ml)increased the frequency of GI bleeding.For patients with severe TBI and treated with routine antacids,the incidence of GI bleeding was 40.91%(9/22)and the mortality rate was 20%(2/10).Conclusions:Low Glasgow coma scale scores,low Hb,high concentrations of gastrin and ACTH(>100 pg/ml)are risk factors and can be predictive values for post-traumatic GI bleeding.Severe TBI patients have high risks of GI bleeding with high mortality.

  15. Five-day regimen of intramuscular or subcutaneous self-administered adrenocorticotropic hormone gel for acute exacerbations of multiple sclerosis: a prospective, randomized, open-label pilot trial

    Directory of Open Access Journals (Sweden)

    Simsarian JP

    2011-07-01

    Full Text Available James P Simsarian, Carol Saunders, D Michelle SmithNeurology Center of Fairfax Ltd, Fairfax, VA, USABackground: Despite over 50 years of experience with adrenocorticotropic hormone (ACTH as a treatment for acute exacerbations of multiple sclerosis, there have been no trials examining the options of the 2–3-week dosing regimen or intramuscular injection protocol used in the original trials. At our clinic, we performed a small, prospective, randomized pilot study to examine the efficacy and safety of, and patient satisfaction with, a short (five-day self-administered ACTH dosing protocol for exacerbations of multiple sclerosis, and to compare the subcutaneous and intramuscular routes of administration.Methods: Patients for this study were recruited from an outpatient treatment clinic. Each patient self-administered natural ACTH gel 80 U/day by subcutaneous or intramuscular injection for five consecutive days and was evaluated at baseline and on days 7 and 14. Patient feedback was collected using the Patient Global Impression of Change (PGI-C, the primary efficacy measure, a patient global visual analog scale, the Expanded Disability Status Scale, a timed walk, the Nine-hole Peg Test, and the Clinical Global Impression of Change.Results: Of the 20 enrolled patients (mean age 39.5 years, 19 completed the study. On day 14, 61.1% of patients (11 of 18 with day 14 scores were treatment responders, and rated their condition as "very much improved" or "much improved" on the PGI-C. The intramuscular group had numerically more responders, but there was no significant difference in the proportion of responders between the intramuscular and subcutaneous groups at day 14 (P = 0.3. The intramuscular route of injection was associated with more injection site pain than the subcutaneous route.Conclusion: A shorter five-day course of intramuscular or subcutaneous ACTH gel may improve symptoms associated with acute exacerbations of multiple sclerosis. Larger

  16. Morning cortisol is lower in obese individuals with normal glucose tolerance

    Directory of Open Access Journals (Sweden)

    Praveen EP

    2011-09-01

    Full Text Available Edavan P Praveen1, Jaya Prakash Sahoo1, Bindu Kulshreshtha2, Madan L Khurana3, Nandita Gupta1, Sada Nand Dwivedi3, Guresh Kumar3, Ariachery C Ammini11Department of Endocrinology, All India Institute of Medical Sciences, 2Ram Manohar Lohia Hospital, 3Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, IndiaBackground: There is no consensus on the role of cortisol in the pathogenesis of obesity and metabolic syndrome (MS. This cross-sectional study aimed to analyze the relationship of morning plasma cortisol and adrenocorticotropic hormone (ACTH levels with body mass index (BMI and glucose tolerance.Subjects and methods: The sample frame was the “Offspring of individuals with diabetes study” database. A total of 358 offspring of individuals with type 2 diabetes mellitus (T2DM and 287 individuals without a known family history of T2DM were recruited for the study. Subjects who were ≥10 years of age were selected from the database for analysis. Subjects with T2DM were excluded. All participants underwent a 75 g oral glucose tolerance test (OGTT, and blood samples were collected at 0, 30, 60, and 120 minutes for glucose, insulin and C-peptide. Plasma cortisol, ACTH, and lipid profile were estimated from the fasting sample.Results: Four hundred and ninety-five participants (305 males [62%] and 190 females [38%] were included in the analysis. ACTH and cortisol levels were higher in normal-weight subjects than in overweight/obese subjects. Both ACTH and cortisol increased as fasting plasma glucose increased. Cortisol levels were significantly lower in offspring of T2DM subjects with MS than in offspring of T2DM subjects without MS. When adjusted for BMI, the significance was marginal. In males, cortisol levels were negatively correlated with early insulin secretion during OGTT (insulinogenic index [0–30] and positively with waist circumference and serum high-density lipoprotein cholesterol. In females, fasting

  17. Oxytocin increases the influence of public service advertisements.

    Science.gov (United States)

    Lin, Pei-Ying; Grewal, Naomi Sparks; Morin, Christophe; Johnson, Walter D; Zak, Paul J

    2013-01-01

    This paper presents a neurophysiologic model of effective public service advertisements (PSAs) and reports two experiments that test the model. In Experiment 1, we show that after watching 16 PSAs participants who received oxytocin, compared to those given a placebo, donated to 57% more causes, donated 56% more money, and reported 17% greater concern for those in the ads. In Experiment 2, we measured adrenocorticotropin hormone (ACTH) and oxytocin levels in blood before and after participants watched a PSA. As predicted by the model, donations occurred when participants had increases in both ACTH and oxytocin. Our results indicate that PSAs with social content that cause OT release will be more effective than those that do not. Our results also explain why some individuals do not respond to PSAs.

  18. Oxytocin increases the influence of public service advertisements.

    Directory of Open Access Journals (Sweden)

    Pei-Ying Lin

    Full Text Available This paper presents a neurophysiologic model of effective public service advertisements (PSAs and reports two experiments that test the model. In Experiment 1, we show that after watching 16 PSAs participants who received oxytocin, compared to those given a placebo, donated to 57% more causes, donated 56% more money, and reported 17% greater concern for those in the ads. In Experiment 2, we measured adrenocorticotropin hormone (ACTH and oxytocin levels in blood before and after participants watched a PSA. As predicted by the model, donations occurred when participants had increases in both ACTH and oxytocin. Our results indicate that PSAs with social content that cause OT release will be more effective than those that do not. Our results also explain why some individuals do not respond to PSAs.

  19. Serum DHEA-S increases in dogs naturally infected with Ehrlichia canis.

    Science.gov (United States)

    Rondelli, M C H; Munhoz, T D; Catandi, P B; Freschi, C R; Palacios Junior, R J G; Machado, R Z; Tinucci-Costa, M

    2015-06-01

    Adrenocortical disturbances are expected in canine ehrlichiosis due to the immunological challenges caused by infection and consequent inflammation. Thus, this study aimed to evaluate the occurrence of adrenocortical hormonal alterations in dogs naturally infected with Ehrlichia canis (n = 21) as positively confirmed by the presence of anti-E. canis antibodies (Dot-ELISA) and nested PCR (nPCR). Serum dehydroepiandrosterone sulfate (DHEA-S) concentrations were assessed via ELISA before and one hour after ACTH stimulation. Another 10 healthy dogs were subjected to the same stimulation protocol and used as controls. The results revealed that baseline and post-ACTH DHEA-S concentrations were significantly greater in sick dogs, regardless of gender, and this finding illustrates the stress induced by naturally acquired ehrlichiosis in dogs.

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

    Science.gov (United States)

    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.

  1. Neurophysiological responses to stressful motion and anti-motion sickness drugs as mediated by the limbic system

    Science.gov (United States)

    Kohl, R. L.; Odell, S.

    1982-01-01

    Performance is characterized in terms of attention and memory, categorizing extrinsic mechanism mediated by ACTH, norepinephrine and dopamine, and intrinsic mechanisms as cholinergic. The cholinergic role in memory and performance was viewed from within the limbic system and related to volitional influences of frontal cortical afferents and behavioral responses of hypothalamic and reticular system efferents. The inhibitory influence of the hippocampus on the autonomic and hormonal responses mediated through the hypothalamus, pituitary, and brain stem are correlated with the actions of such anti-motion sickness drugs as scopolamine and amphetamine. These drugs appear to exert their effects on motion sickness symptomatology through diverse though synergistic neurochemical mechanisms involving the septohippocampal pathway and other limbic system structures. The particular impact of the limbic system on an animal's behavioral and hormonal responses to stress is influenced by ACTH, cortisol, scopolamine, and amphetamine.

  2. Plasma levels of heat shock protein 72 (HSP72) and beta-endorphin as indicators of stress, pain and prognosis in horses with colic.

    Science.gov (United States)

    Niinistö, Kati E; Korolainen, Raija V; Raekallio, Marja R; Mykkänen, Anna K; Koho, Ninna M; Ruohoniemi, Mirja O; Leppäluoto, Juhani; Pösö, A Reeta

    2010-04-01

    A prospective observational study was performed to evaluate whether the plasma concentration of heat shock protein 72 (HSP72) or beta-endorphin is related to clinical signs, blood chemistry, or severity of pain of colic. Seventy-seven horses with colic and 15 clinically healthy controls were studied. The horses were divided into four groups which reflected increasing severity of colic, from normal control horses to horses with mild, moderate and severe colic. Blood samples were collected before any treatment. Packed cell volume (PCV) and plasma HSP72, beta-endorphin, cortisol, adrenocorticotropic hormone (ACTH) and lactate concentrations were measured. Plasma beta-endorphin was related with severity of colic and survival, as well as with plasma cortisol, ACTH and lactate concentrations, heart rate, PCV and pain score. High plasma HSP72 concentration may indicate circulatory deficits, but was not associated with clinical signs of colic. Plasma lactate still seemed to be the most useful single prognostic parameter in horses with colic.

  3. Smoking is associated with increased adrenal responsiveness, decreased prolactin levels and a more adverse lipid profile in 650 white patients with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Mumm, Hanne; Hougaard, David M.;

    2011-01-01

    We investigated the associations between smoking status and metabolic risk factors and sex hormones in polycystic ovary syndrome (PCOS). The study was designed as a retrospective trans-sectional study including 650 white premenopausal women with the diagnoses hirsutism or PCOS divided according...... to smoking status: non-smokers (NS-PCOS = 390) and smokers (S-PCOS = 260). One hundred and nineteen healthy women were studied as controls (NS-Control = 105, S-Control = 14). Patients and controls underwent clinical evaluation, hormone analyses, transvaginal ultrasound, oral glucose tolerance tests (OGTT......) and adrenocorticotropic hormone (ACTH) tests. S-PCOS has significantly higher fasting lipid profile and 17-hydroxyprogesterone levels (basal and ACTH-stimulated) than NS-PCOS patients, whereas prolactin levels were decreased. No significant differences were found in body composition and measures of insulin resistance...

  4. Stress and stereotypic behaviour in mink (Mustela vison)

    DEFF Research Database (Denmark)

    Malmkvist, Jens; Jeppesen, L L; Palme, R

    2011-01-01

    We examined whether female mink with low (LS) and high (HS) occurrence of stereotypic behaviour differ in their adrenocortical activity in baseline conditions or in response to immobilisation (Experiment 1), handling, adrenocorticotropic hormone (ACTH) challenge (Experiment 2) and excretion...... 4-20 h after the handling (P = 0.001). In Experiment 3 (n = 16), the excretion of infused (3)H-cortisol did not differ between LS and HS mink. Stereotypic behaviour is concurrent with higher baseline concentrations of FCM, which cannot be explained by a greater adrenocortical reactivity...... of circulating cortisol (Experiment 3). Faeces are the predominating excretory route of cortisol (83%), with peak concentrations after 4.2 h (urine: 3.4 h). Faecal cortisol metabolites (FCMs) reflected changes in relation to handling/ACTH challenge. In Experiment 1 (n = 162), HS mink had approximately 54% higher...

  5. [Eutopic parturition: psychoprophylaxis or extradural analgesia. Influence on the endocrine response].

    Science.gov (United States)

    Carrasco, M S; Iglesias, J; Freire, J; Martín, M L; Marín Santana, A; Cobo, I; García Rendón, A

    1989-01-01

    Prolactin, ACTH, cortisol and HGH levels have been studied on 30 pregnant women in three different periods: during the labour, at the delivery and 24 hours later. They were divided into 3 groups depending on the analgesia: I) no analgesia (n = 10); II) psychoprophylaxis (n = 10), and III) extradural analgesia (n = 10). Prolactin levels increased during delivery and 24 hours later. A significant increase of ACTH levels (p less than 0.01) was observed during the delivery in the 3 groups even though they were under hasal values 24 hours later. Cortisol increased 38% (p less than 0.01) and 52% (p less than 0.02) in II and III groups, respectively during the delivery. No difference was found with HGH. Our results suggest that endocrine response modified by labour and delivery doesn't change with different analgesia techniques.

  6. Angiotensin II in the brain and pituitary: contrasting roles in the regulation of adenohypophyseal secretion.

    Science.gov (United States)

    Ganong, W F

    1989-01-01

    Angiotensin II (AII) is present in gonadotropes in rats, and there are AII receptors on lactotropes and corticotropes. AII may be a paracrine mediator that stimulates the secretion of prolactin and adrenocorticotropin (ACTH) at the level of the pituitary, but additional research is needed to define its exact role. Angiotensinogen may also reach the gonadotropes via a paracrine route. On the other hand, there is considerable evidence that brain AII stimulates the secretion of luteinizing hormone (LH) by increasing the secretion of LH-releasing hormone, and that this effect is due to AII-mediated release of norepinephrine from noradrenergic nerve terminals in the preoptic region of the hypothalamus. In addition, brain AII inhibits the secretion of prolactin, probably by increasing the release of dopamine into the portal hypophyseal vessels. Circulating AII stimulates the secretion of a third anterior pituitary hormone, ACTH, by acting on one or more of the circumventricular organs to increase the secretion of corticotropin-releasing hormone.

  7. Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Gallium-68 DOTA-TATE Positron Emission Tomography/Computed Tomography: Scintigraphic Changes of Adrenal Glands Following Management of Ectopic Cushing's Syndrome by Steroidogenesis Inhibitors.

    Science.gov (United States)

    Huang, Yu-Ting; Aziz, Shaikh Irfan; Ravi Kumar, Aravind S

    2014-09-01

    In the era of emerging functional imaging techniques, an understanding of the effects of hormonal therapies on the scintigraphic appearance of endocrine organs is desirable to minimize the erroneous scan interpretation. The mechanisms by which changes in the scintigraphic appearance of endocrine organs occur however sometimes remain ambiguous. This case demonstrates the gallium-68 (Ga-68) DOTA-TATE positron emission tomography/computed tomography (CT) appearance of adrenal glands following management with steroidogenesis inhibitors. The potential mechanisms underlying this change are discussed. A 17-year-old boy with adrenocorticotropic hormone (ACTH) dependent Cushing's syndrome secondary to ectopic ACTH secretion underwent pre- and post-metyrapone and dexamethasone treatment Ga-68 DOTA-TATE scans 4 months apart. Pretreatment, both adrenals demonstrated normal symmetrical prominent Ga-68 DOTA-TATE uptake and normal CT appearance. The posttherapy scan revealed marked symmetrical suppression of Ga-68 DOTA-TATE uptake, but with bilateral adrenal hypertrophy on CT.

  9. Strongyloides stercoralis Hyperinfection Syndrome Presenting as Severe, Recurrent Gastrointestinal Bleeding, Leading to a Diagnosis of Cushing Disease

    Science.gov (United States)

    Yee, Brittany; Chi, Nai-Wen; Hansen, Lawrence A.; Lee, Roland R.; U, Hoi-Sang; Savides, Thomas J.; Vinetz, Joseph M.

    2015-01-01

    A 50-year-old male immigrant from Ethiopia presented for consultation after 3 years of hematochezia/melena requiring > 25 units of blood transfusions. Physical examination revealed severe proximal muscle wasting and weakness, central obesity, proptosis, and abdominal striae, accompanied by eosinophilia, elevated hemoglobin A1c, elevated 24-hour urinary cortisol, lack of suppression of 8 am cortisol levels by 1 mg dexamethasone, and inappropriately elevated random adrenocorticotropic hormone (ACTH) level. Histopathological examination of gastrointestinal biopsies showed large numbers of Strongyloides stercoralis, indicating Strongyloides hyperinfection. Treatment with 2 days of ivermectin led to resolution of gastrointestinal bleeding. This syndrome was due to chronic immunosuppression from a pituitary ACTH (corticotroph) microadenoma, of which resection led to gradual normalization of urine cortisol, improved glycemic control, resolution of eosinophilia, and no recurrence of infection. PMID:26195463

  10. Cushing’s disease

    Directory of Open Access Journals (Sweden)

    Castinetti Frederic

    2012-06-01

    Full Text Available Abstract Cushing’s disease, or pituitary ACTH dependent Cushing’s syndrome, is a rare disease responsible for increased morbidity and mortality. Signs and symptoms of hypercortisolism are usually non specific: obesity, signs of protein wasting, increased blood pressure, variable levels of hirsutism. Diagnosis is frequently difficult, and requires a strict algorithm. First-line treatment is based on transsphenoidal surgery, which cures 80% of ACTH-secreting microadenomas. The rate of remission is lower in macroadenomas. Other therapeutic modalities including anticortisolic drugs, radiation techniques or bilateral adrenalectomy will thus be necessary to avoid long-term risks (metabolic syndrome, osteoporosis, cardiovascular disease of hypercortisolism. This review summarizes potential pathophysiological mechanisms, diagnostic approaches, and therapies.

  11. Unmasking sarcoidosis following surgery for Cushing disease

    DEFF Research Database (Denmark)

    Diernaes, Jon E F; Bygum, Anette; Poulsen, Per L

    2016-01-01

    We present a patient with Cushing disease apparently suppressing sarcoidosis, which was unmasked following surgical resection of a pituitary adrenocorticotropin (ACTH)-producing microadenoma. Case report and a short review of the literature published in this area. A 46-year-old Caucasian woman pr...... successful treatment of Cushing syndrome may have a flare-up or emergence of a corticosteroid-responsive disease.......We present a patient with Cushing disease apparently suppressing sarcoidosis, which was unmasked following surgical resection of a pituitary adrenocorticotropin (ACTH)-producing microadenoma. Case report and a short review of the literature published in this area. A 46-year-old Caucasian woman...... for which the patient underwent transphenoidal resection. Maintenance corticosteroid therapy was implemented, and the signs and symptoms of Cushing disease began to resolve. Three months after surgery, multiple erythematous painful nodules developed on the patient's arms. Erythema nodosum (EN) was diagnosed...

  12. Cushing’s Syndrome Secondary to isolated Micronodular Adrenocortical Disease (iMAD) associated with Rapid Onset Weight Gain and Negative Abdominal MRI Findings in a 3 year old Male

    Science.gov (United States)

    Henry, Rohan K.; Keil, Margaret F.; Stratakis, Constantine A.; Fechner, Patricia Y.

    2011-01-01

    Cushing’s syndrome (CS) is uncommon in childhood. CS may be either dependent or independent of adrenocorticotrophic hormone (ACTH). ACTH independent micronodular adrenocortical (MAD) disease may present in the second to third decade of life or between ages 2–3years. It may occur in isolation, or as a part of the Carney complex and it represents an elusive entity to diagnose. We present a 3 year 7 month old boy with isolated MAD (iMAD). Abdominal CT revealed prominent mildly lobulated anteromedial margin of adrenals with nodular appearance. Cardiac echo, thyroid and testicular ultrasounds performed as a work up for Carney complex were normal. Bilateral adrenalectomy confirmed MAD as the cause of CS. We present the history’ and identification of a unique case of iMAD. PMID:20662336

  13. Bilateral inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin-dependent Cushing's syndrome with unknown origin%岩下窦静脉取血在疑难ACTH依赖性库欣综合征诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    卢琳; 金征宇; 任祖渊; 王任直; 幸兵; 顾锋; 张晓波; 陆召麟; 曾正陪; 刘怀成; 童安莉; 岳欣; 付勇

    2009-01-01

    Objective To evaluate the value of inferior petrosal sinus sampling in ACTH-dependent Cushing's syndrome with unknown origin.Method IPSS was carried out for the diagnosis of 20 cases of ACTH dependent Cushing's syndrome who had not been identified of diagnosis after a series of dexamethasone suppression tests and radiological examinations from Jan,2008 to Jan 2009.The ratio of plasma ACTH concentration between inferior petrosal sinus and peripheral veins was assayed.The sensitivity and specificity of diagnosis of the Cushing's disease were estimated.Results The basal ratio of ACTH concentration between inferior petrosal sinus and peripheral veins was >2 in 18 cases.13 cases underwent transphenoidal surgery with pathological diagnosis of pituitary ACTH adenoma;1 patient chose γ knife treatment and 4 patients chose somatostatin therapy with relieve of the disease.The basal ratio of ACTH concentration between inferior petrosal sinus and peripheral veins was <2 in 2 cases. One pulmonary node was removed by surgery with pathological diagnosis of carcinoid in 1 patient.One transphenoidal surgery was still undergone according to the clinical features in the other patient with pathological diagnosis of pituitary ACTH adenoma. The sensitivity and specify of inferior petrosal sinus sampling for the diagnosis of Cushing's disease in this study were 93% and 100% respectively.Conclusion Inferior petrosal sinus sampling is a safe technique with infrequent complications. It has great value in the differential diagnosis of ACTH-dependent Cushing's disease with unknown origin.%目的 探讨岩下窦静脉取血(IPSS)在疑难库欣综合征诊断中的价值.方法 对20例疑难库欣综合征行岩下窦和外周静脉取血,测定血ACTH浓度比,评价其对库欣病诊断的敏感性和特异性.结果 18例患者的岩下窦与外周静脉血ACTH的比值>2,其中13例行经蝶窦垂体术后病理为垂体ACTH腺瘤;1例行鞍区γ-刀治疗、4例行生

  14. 以顽固性低血钾为首发的异位促肾上腺皮质激素综合征2例报告

    Institute of Scientific and Technical Information of China (English)

    张雅娟

    2008-01-01

    @@ 异位促肾上腺皮质激素(ACTH)综合征(ecotopic adrenal corticotropic hormone syndrome,EAS)是Cushing综合征的一种特殊类型,是由于垂体以外肿瘤分泌大量ACTH,刺激肾上腺皮质分泌过量的糖皮质激素,进而导致的临床综合征[1].本研究收集2007年就诊于我院的以顽固性低血钾为首发的EAS 2例患者,现将临床资料报道如下.

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

    Science.gov (United States)

    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.

  16. Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions

    DEFF Research Database (Denmark)

    Jansen, Steffy W; Roelfsema, Ferdinand; Akintola, Abimbola A;

    2015-01-01

    of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls. DESIGN: Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls...... for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation...... not differ between offspring and controls. In addition, no significant differences in feedforward and feedback synchrony and adrenal gland ACTH responsivity were observed between groups. CONCLUSIONS: These results suggest that familial longevity is not associated with major differences in HPA-axis activity...

  17. Changes of hypothalamus-pituitary hormones in patients after total removal of craniopharyngiomas

    Institute of Scientific and Technical Information of China (English)

    周忠清; 石祥恩

    2004-01-01

    Background This paper aimed to elucidate the changes of hypothalamus-pituitary hormones in patients after total removal of craniopharyngiomas.Methods A total of 40 patients with craniopharyngiomas received surgery. The levels of triiodothyronine (T3), thyroxine (T4), thyrotropic hormone (TSH), antidiuretic hormone (ADH), and adrenocorticotropin (ACTH) were measureed in the 40 patients before surgery and one week after surgery respectively.Results Twenty-eight patients (70%) had hypothyroidism before surgery, but 38 (95%) had hypothyroidism after surgery (P0.05), whereas those of ACTH were (23.97±2.69) pg/ml and (15.60±1.91) pg/ml respectively (P<0.05).Conclusions Hormone deficits after total removal of craniopharyngioma appear to be the common complication of surgery. Hypothyroidism and diabetes insipidus are more frequent after surgery than before surgery. Thyroxine and glucocorticoids should be administered routinely after total removal of craniopharyngioma.

  18. Relationship between plasma and tissue corticosterone in laying hens (Gallus gallus domesticus): implications for stress physiology and animal welfare.

    Science.gov (United States)

    Ralph, C R; Hemsworth, P H; Leury, B J; Tilbrook, A J

    2015-01-01

    This study directly compared the dynamics of change in plasma corticosterone concentration with the dynamics of change in tissue corticosterone concentration in laying hens. In concert, we measured the rate of gluconeogenesis, glycogenesis, and glycolysis in the liver, kidney, skeletal muscle, and heart. We evaluated these changes acutely, over 3 h in response to an adrenocorticotropic hormone (ACTH) injection, and chronically, over 24 h in response to food and water deprivation. In response to ACTH injection, there was a significant (P physiology under acute and chronic conditions. Our data suggest that extending our evaluation of stress to the site of corticosterone action, that is, the target tissue, may enhance our ability to evaluate stress and the welfare of laying hens.

  19. Strongyloides stercoralis Hyperinfection Syndrome Presenting as Severe, Recurrent Gastrointestinal Bleeding, Leading to a Diagnosis of Cushing Disease.

    Science.gov (United States)

    Yee, Brittany; Chi, Nai-Wen; Hansen, Lawrence A; Lee, Roland R; U, Hoi-Sang; Savides, Thomas J; Vinetz, Joseph M

    2015-10-01

    A 50-year-old male immigrant from Ethiopia presented for consultation after 3 years of hematochezia/melena requiring > 25 units of blood transfusions. Physical examination revealed severe proximal muscle wasting and weakness, central obesity, proptosis, and abdominal striae, accompanied by eosinophilia, elevated hemoglobin A1c, elevated 24-hour urinary cortisol, lack of suppression of 8 am cortisol levels by 1 mg dexamethasone, and inappropriately elevated random adrenocorticotropic hormone (ACTH) level. Histopathological examination of gastrointestinal biopsies showed large numbers of Strongyloides stercoralis, indicating Strongyloides hyperinfection. Treatment with 2 days of ivermectin led to resolution of gastrointestinal bleeding. This syndrome was due to chronic immunosuppression from a pituitary ACTH (corticotroph) microadenoma, of which resection led to gradual normalization of urine cortisol, improved glycemic control, resolution of eosinophilia, and no recurrence of infection.

  20. Cortisol secretion in patients with normoprolactinemic amenorrhea

    DEFF Research Database (Denmark)

    Boesgaard, S; Hagen, C; Andersen, A N

    1988-01-01

    Patients with functional amenorrhea have raised central dopaminergic activity and opioid-mediated GnRH inhibition leading to inhibition of hypothalamic-pituitary-ovarian function. In the present study, basal serum cortisol and ACTH levels were measured in normoprolactinemic amenorrheic patients...... with (N = 14) and without (N = 7) insulin-dependent diabetes mellitus. Basal serum cortisol levels was significantly (P less than 0.01) elevated in patients with normoprolactinemic amenorrhea compared with normal women. Basal serum cortisol was significantly (P less than 0.02) elevated in amenorrheic...... diabetic patients compared with menstruating diabetic women. In the amenorrheic groups both cortisol and ACTH levels increased significantly (P less than 0.01) after dopamine D-2 receptor blockade, whereas no hormonal changes occurred in the control groups. It is concluded that patients...

  1. Pituitary tumor with gigantism, acromegaly and preclinical Cushing's disease diagnosed from the 10th row.

    Science.gov (United States)

    Tourtelot, John B; Vesely, David L

    2013-08-01

    A 7'3" basketball player was noted to have 2 to 3 times thicker tissue in his hands than 6'10" players by an endocrinologist sitting 10 rows above the player in a basketball arena. This led to the diagnosis of pituitary gigantism where the history revealed that he was 7'3" at 15 years of age. At age 19 when the acryl enlargement was noted, a diagnostic workup revealed elevated growth hormones and insulin-like growth factor 1 (IGF-1) with a 2 × 1.3 cm pituitary tumor. His history suggested that his epiphyseal plates had closed at age 15, and because he continued to produce IGF-1, he now has acromegaly. His elevated adrenocorticotropic hormone (ACTH) before surgery suggests that he also had preclinical Cushing's disease. After pituitary transsphenoidal surgery, all acryl enlargement in hands and ligaments disappeared. His growth hormone, IGF-1 and ACTH returned to normal 2 weeks after surgery.

  2. A Case Report of Multiple Endocrine Neoplasia Type IIa Associated with Cushing Syndrome

    Directory of Open Access Journals (Sweden)

    Sh. Borzouei

    2013-10-01

    Full Text Available Introduction: Multiple endocrine neoplasia type IIa (MEN IIa is an autosomal dominant syn-drome characterized bypheochromocytoma ,medullary thyroid carcinoma and hyperparathy-roidism. Pheochromocytoma approximately occurs in 50% of patients with MEN IIa. This tumor has the capacity to produce ACTH ectopically and becomes manifest like Cushing syndrome,although it is very rare. Case Report: We report a 26-year-old woman patient with severe muscle weakness, skin le-sions in extremity, hypertension, new onset diabetes and in the laboratory data hypokalemia, metabolic alkalosis, high serum level of cortisol, metanephrine, normetanephrine, calcitonin and bilateral adrenal mass in computed tomography as the first clinical manifestations of an ACTH-secreting pheochromocytoma. Conclusion: In the patients with hypertension, new onset diabetes and hypokalemia Cushing syndrome and pheochromocytoma should always be ruled out. (Sci J Hamadan Univ Med Sci 2013; 20 (3:260-265

  3. Nelson syndrome: historical perspectives and current concepts.

    Science.gov (United States)

    Hornyak, Mark; Weiss, Martin H; Nelson, Don H; Couldwell, William T

    2007-01-01

    The appearance of an adrenocorticotropic hormone (ACTH)-producing tumor after bilateral adrenalectomy for Cushing disease was first described by Nelson in 1958. The syndrome that now bears his name was characterized by hyperpigmentation, a sellar mass, and increased plasma ACTH levels. The treatment of Cushing disease has changed drastically since the 1950s, when the choice was adrenalectomy. Thus, the occurrence, diagnosis, and treatment of Nelson syndrome have changed as well. In the modern era of high-resolution neuroimaging, transsphenoidal microneurosurgery, and stereotactic radiosurgery, Nelson syndrome has become a rare entity. The authors describe the history of the diagnosis and treatment of Nelson syndrome. In light of the changes described, the authors believe this disease must be reevaluated in the contemporary era and a modern paradigm adopted.

  4. Development of the adrenal axis in the neonatal rat

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, Ronnie

    1977-01-01

    Plasma corticosterone and ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, under a variety of experimental conditions, to obtain more information on the postnatal development of the rat hypothalamo-adrenal (HHA) axis. The results indicate that: (1) there is a diminution followed by an increase in responsiveness of the adrenal gland, but the pituitary response to direct hormonal stimulation is unchanged during the first three postnatal weeks; (2) continued stimulation of the adrenal by ACTH or of the central nervous system (CNS) or hypothalamus by corticosterone is necessary during early postnatal development to allow normal maturation of the HHA axis; and (3) feedback inhibition is operative by birth, at least to a moderate degree. Taken together, the studies suggest that both the adrenal and pituitary glands are potentially functional at birth, but that the hypothalamic and CNS mediators of the stress response are not mature until at least the second or third postnatal week. (ERB)

  5. Landau-Kleffner syndrome : a case report.

    Directory of Open Access Journals (Sweden)

    Raybarman C

    2002-04-01

    Full Text Available A healthy 5 year old boy developed aphasia, attention disorder and hyperkinesia preceded by transient formed visual hallucinations and emotional outburst, immediately after a stressful event of forced separation from his father. EEG showed generalized epileptiform activity. He was diagnosed as Landau-Kleffner syndrome (LKS. CT and MRI of the brain were normal. SPECT showed left mesial temporal hypoperfusion. He improved on antiepileptics and ACTH.

  6. Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner.

    Science.gov (United States)

    Ulrich-Lai, Yvonne M; Figueiredo, Helmer F; Ostrander, Michelle M; Choi, Dennis C; Engeland, William C; Herman, James P

    2006-11-01

    The adrenal gland is an essential stress-responsive organ that is part of both the hypothalamic-pituitary-adrenal axis and the sympatho-adrenomedullary system. Chronic stress exposure commonly increases adrenal weight, but it is not known to what extent this growth is due to cellular hyperplasia or hypertrophy and whether it is subregion specific. Moreover, it is not clear whether increased production of adrenal glucocorticoid after chronic stress is due to increased sensitivity to adrenocorticotropic hormone (ACTH) vs. increased maximal output. The present studies use a 14-day chronic variable stress (CVS) paradigm in adult male rats to assess the effects of chronic stress on adrenal growth and corticosterone steroidogenesis. Exogenous ACTH administration (0-895 ng/100 g body wt) to dexamethasone-blocked rats demonstrated that CVS increased maximal plasma and adrenal corticosterone responses to ACTH without affecting sensitivity. This enhanced function was associated with increased adrenal weight, DNA and RNA content, and RNA/DNA ratio after CVS, suggesting that both cellular hyperplasia and hypertrophy occurred. Unbiased stereological counting of cells labeled for Ki67 (cell division marker) or 4,6-diamidino-2-phenylindole (nuclear marker), combined with zone specific markers, showed that CVS induced hyperplasia in the outer zona fasciculata, hypertrophy in the inner zona fasciculata and medulla, and reduced cell size in the zona glomerulosa. Collectively, these results demonstrate that increased adrenal weight after CVS is due to hyperplasia and hypertrophy that occur in specific adrenal subregions and is associated with increased maximal corticosterone responses to ACTH. These chronic stress-induced changes in adrenal growth and function may have implications for patients with stress-related disorders.

  7. The Defecation Index as a Measure of Emotionality: Questions Raised by HPA Axis and Prolactin Response to Stress in the Maudsley Model.

    Science.gov (United States)

    Blizard, David A; Eldridge, J Charles; Jones, Byron C

    2015-05-01

    The Maudsley Reactive and Maudsley Non-Reactive strains have been selectively bred for differences in open-field defecation (OFD), a putative index of stress. We investigated whether variations in the hypothalamic-pituitary-adrenal (HPA) axis are correlated with strain differences in OFD in the Maudsley model. Exposure to the open-field test did not result in increases in ACTH in male rats of either strain and there were no strain differences in the large increases in ACTH and corticosteroid that occurred in response to intermittent footshock. Parallel studies of prolactin showed that Maudsley Reactive rats had greater response to the open-field and to footshock than Maudsley Non-Reactive rats. The lack of correlation between strain differences in OFD and reactivity of the HPA axis is consistent with the idea that HPA response to stress and OFD reflect the output of different neural systems and that individual differences in emotionality, as indexed by OFD do not influence other measures of stress-reactivity in a simple manner, if at all. The reactivity of the prolactin system to the open-field test and lack of response of ACTH to the same situation is consistent with the idea that the prolactin system is sensitive to lower levels of stress than the HPA axis, a finding at variance with the presumed extreme sensitivity of the latter system. Earlier comparisons of the HPA axis in these strains implicate local factors such as neuropeptide-Y peptide in the adrenal in attenuating the response of the adrenal cortex to ACTH and hints at the complexity of regulation of the HPA axis.

  8. HPA axis reactivity to pharmacologic and psychological stressors in euthymic women with histories of postpartum versus major depression.

    Science.gov (United States)

    Ferguson, Elizabeth H; Di Florio, Arianna; Pearson, Brenda; Putnam, Karen T; Girdler, Susan; Rubinow, David R; Meltzer-Brody, Samantha

    2017-03-01

    It is unclear whether women with a history of postpartum depression (PPD) have residual, abnormal hypothalamic-pituitary-adrenal (HPA) axis reactivity, as has been reported in major depression (MDD). Further unclear is whether the abnormalities in HPA axis reactivity associated with MDD represent a stable, underlying predisposition or a state-dependent phenomenon. This study sought the following: (1) to determine if euthymic postpartum women with a history of depression have an abnormal HPA axis reactivity to pharmacologic and psychological challenges and (2) to compare HPA reactivity in women with histories of PPD versus MDD. As a secondary objective, we wanted to determine the influence of trauma history on HPA axis function. Forty-five parous (12-24 months postpartum), euthymic women with history of MDD (n = 15), PPD (n = 15), and controls (n = 15) completed pharmacologic (dexamethasone/corticotropin-releasing hormone (CRH) test [DEX/CRH]) and psychological (Trier social stress test [TSST]) challenges during the luteal phase. Outcome measures were cortisol and adrenocorticotropic hormone (ACTH) response after DEX/CRH, and blood pressure, heart rate, epinephrine, norepinephrine, and cortisol response during the TSST. All groups had robust cortisol and ACTH response to DEX/CRH and cortisol response to TSST. Groups did not differ significantly in cortisol or ACTH response to DEX/CRH or in blood pressure, heart rate, epinephrine, norepinephrine, or cortisol response to TSST. Cortisol/ACTH ratio did not differ significantly between groups. Trauma history was associated with decreased cortisol response to DEX/CRH in women with histories of MDD, which was not significant after correction (F 8,125, p = 0.02, Greenhouse-Geisser corrected p = 0.11). Currently euthymic women with histories of MDD or PPD did not demonstrate residual abnormal stress responsivity following administration of either a pharmacologic or psychological stressor.

  9. Post-natal stress-induced endocrine and metabolic alterations in mice at adulthood involve different pro-opiomelanocortin-derived peptides.

    Science.gov (United States)

    Loizzo, Stefano; Campana, Gabriele; Vella, Stefano; Fortuna, Andrea; Galietta, Gabriella; Guarino, Irene; Costa, Loredana; Capasso, Anna; Renzi, Paolo; Frajese, Giovanni V; Franconi, Flavia; Loizzo, Alberto; Spampinato, Santi

    2010-11-01

    In previous investigations we added a physical stress (mild pain) to the "classical" post-natal psychological stress in male mice, and we found that this combination produced a series of dysmetabolic signs very similar to mild human type-2 diabetes. Here, for the first time we demonstrate that within this diabetes model at least two groups of signs depend on the unbalance of two different endogenous systems. Newborn male mice were daily exposed to stressful procedures for 21 days (brief mother separation plus sham injection). Other groups underwent the same procedure, and also received naloxone (Na) to block μ-δ endogenous receptors, or a phosphorothioate antisense oligonucleotide (AS) directed against pro-opiomelanocortin (POMC)-mRNA [to block adrenocorticotropin (ACTH)- and POMC-derived opioid peptides]. Adult mice which received only post-natal stress increased body weight (+7.5%), abdominal overweight (+74%), fasting glycemia (+43%), plasma corticosterone (+110%), plasma (+169%) and pituitary (+153%) ACTH levels. Conversely, hypothalamic ACTH and corticotropin-releasing hormone (CRH) were reduced (-70% and -75%, respectively). Neonatal AS administration reverted all parameters to control values. Neonatal naloxone had little or no influence on glucose, corticosterone, ACTH, CRH levels, whereas it prevented body overweight and abdominal overweight. We conclude that, within this type-2 diabetes model in male mice at least two endocrino-neurohumoral systems are damaged, one concerning the opioid system, and the other concerning HPA hormones. The use of the two drugs was of primary importance to demonstrate this statement, and to demonstrate that these two groups of signs could be defined as "separate entities" following our complex post-natal stress model.

  10. Fecal cortisol metabolite analysis for noninvasive monitoring of adrenocortical function in the cheetah (Acinonyx jubatus).

    Science.gov (United States)

    Terio, K A; Citino, S B; Brown, J L

    1999-12-01

    A radioimmunoassay was validated for quantifying excreted cortisol metabolites in cheetah (Acinonyx jubatus) feces. High-performance liquid chromatography analysis indicated that immunoreactivity was associated with a water-soluble metabolite in fecal extracts from males and females. None of the immunoreactivity corresponded with free cortisol or corticosterone but rather was associated with a more polar, unidentified metabolite. To determine the biologic relevance of excreted immunoreactive cortisol metabolites, cheetahs were exposed to a variety of situations anticipated to increase cortisol secretion. First, to assess acute changes in adrenal activity, adrenocorticotropic hormone (ACTH; 400 IU i.m.) was administered to two adult males and two adult females. Pre-ACTH baseline serum cortisol and fecal cortisol metabolite concentrations varied among individuals. Serum cortisol concentrations were elevated above baseline within 10 min of ACTH injection, followed by corresponding increases in fecal cortisol metabolite concentrations (690-4,194% above baseline) 48 hr later in three of four cheetahs. In the fourth cheetah, a smaller increase (334% above baseline) in fecal cortisol metabolite excretion was observed 96 hr after ACTH injection. Seven cheetah females also were subjected to a variety of potentially stressful manipulations, including immobilization, translocation, and introduction to a male to assess the ability of this technique to detect physiologic changes in adrenal activity. Increased fecal corticoid metabolite excretion was observed 24-72 hr after exposure to these exogenous stressors. Results indicate that adrenocortical activity can be monitored noninvasively in the cheetah through analysis of these metabolites. This technique could be valuable for evaluating, and thus optimizing, environmental and management conditions and for investigating the role of stress in disease pathogenesis and the usually poor reproductive performance of this species in

  11. Validation of a fecal glucocorticoid metabolite assay for collared peccaries (Pecari tajacu).

    Science.gov (United States)

    Coradello, Mara Adriana; Morais, Rosana Nogueira; Roper, James; Spercoski, Katherinne Maria; Massuda, Thiago; Nogueira, Selene Siqueira Cunha; Nogueira-Filho, Sérgio Luiz Gama

    2012-06-01

    The possibility of assessing endogenous adrenal activity in the collared peccary (Pecari tajacu) was tested by using an adrenocorticotropic hormone (ACTH) challenge in a fecal glucocorticoid metabolite (FGM) assay. Feces were collected from 12 captive adult male peccaries beginning 48 hr prior to challenge; six of these animals received the challenge as an ACTH injection and the other six were injected with saline solution. Feces collection ended 120 hr after injections. As a control, feces were collected for eight consecutive days from another six adult male peccaries that remained in their original mixed-sex herds in semiconfined paddocks. All feces samples were freeze-dried, extracted by an ethanol vortex method, and assayed for glucocorticoids by means of an enzyme immunoassay. FGM concentrations were compared between the treatments by a repeated measures analysis of variance (ANOVA) followed by a post hoc Tukey test. The assay is reliable but, instead of the usual proportion of 1:50 in ethanol (fecal mass:solvent), 1:10 is recommended for best extraction of FGM. Baseline FGM concentrations were similar among the ACTH, saline, and control treatments (29.7 +/- 11.2 ng/g(-1) dry feces) during the 48 hr before the challenge. The ACTH group reached an FGM excretion peak at 24 hr post-treatment, followed by a decline, while in the control and saline groups FGM levels remained relatively constant. Therefore, the fecal glucocorticoid metabolite assay reflects endogenous adrenal activity in the collared peccary and is a powerful tool for noninvasive stress monitoring in peccaries.

  12. The renin-angiotensin system and the central nervous system.

    Science.gov (United States)

    Ganong, W F

    1977-04-01

    One of several factors affecting the secretion of renin by the kidneys is the sympathetic nervous system. The sympathetic input is excitatory and is mediated by beta-adrenergic receptors, which are probably located on the membranes of the juxtaglomerular cells. Stimulation of sympathetic areas in the medulla, midbrain and hypothalamus raises blood pressure and increases renin secretion, whereas stimulation of other parts of the hypothalamus decreases blood pressure and renin output. The centrally active alpha-adrenergic agonist clonidine decreases renin secretion, lowers blood pressure, inhibits ACTH and vasopressin secretion, and increases growth hormone secretion in dogs. The effects on ACTH and growth hormone are abolished by administration of phenoxybenzamine into the third ventricle, whereas the effect on blood pressure is abolished by administration of phenoxybenzamine in the fourth ventricle without any effect on the ACTH and growth hormone responses. Fourth ventricular phenoxybenzamine decreases but does not abolish the inhibitory effect of clonidine on renin secretion. Circulating angiotensin II acts on the brain via the area postrema to raise blood pressure and via the subfornical organ to increase water intake. Its effect on vasopressin secretion is debated. The brain contains a renin-like enzyme, converting enzyme, renin substrate, and angiotensin. There is debate about the nature and physiological significance of the angiotensin II-generating enzyme in the brain, and about the nature of the angiotensin I and angiotensin II that have been reported to be present in the central nervous system. However, injection of angiotensin II into the cerebral ventricles produces drinking, increased secretion of vasopressin and ACTH, and increased blood pressure. The same responses are produced by intraventricular renin. Angiotensin II also facilitates sympathetic discharge in the periphery, and the possibility that it exerts a similar action on the adrenergic neurons

  13. Drug: D03593 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03593 Drug Corticotropin zinc hydroxide (USP); Corticotropin-Zinc (TN) Hormone [adr...enocorticotropic]; Glucocorticoid; Diagnostic aid [adrenocortical insufficiency] ATC code: H01AA01 melanoco...ONES AND ANALOGUES H01AA ACTH H01AA01 Corticotropin D03593 Corticotropin zinc hydroxide (USP) USP drug class...ification [BR:br08302] Hormonal Agents, Stimulant/Replacement/Modifying (Adrenal)... Corticotropin D03593 Corticotropin zinc hydroxide (USP) Target-based classification of drugs [BR:br08310] G

  14. United States Air Force Summer Faculty Research Program (1984). Program Management Report. Volume 3

    Science.gov (United States)

    1984-12-01

    and Steroidogenesis of Enzyme - and ACTH-treated Y-1 Mouse Adrenal Tumor Cells, ’ Cell Biology International Reports, Vol. 8, pp. 483-509 (1984). 9...obtained by a modified Elson-Morgon test after hydrolysis of the sample in 6N hydrochloric acid in sealed tubes at 95 0 C for six hours (10). Spectra...determination of plasma concentrations of cholesterol, high- -" den3lty lipoprotein-associated choletterol, triglycerides and fibrinogen, it may eventually

  15. The Relationship Between Beta-Adrenoreceptor Density and Immune Function Before and After Acute Stressor Exposure

    Science.gov (United States)

    1994-10-12

    should also be examined for their influences on immunity (eg. growth hormone, ACTH, prolactin ). Since~­ adrenoreceptors only accounted for between 14 and...raisins, prunes, orange peel, banana or pineapple. Cheese bread, nut bread containing walnuts. Raisin bran. Desserts containing walnuts, sour cream or...fruit cocktail with pineapple. Tomato, broad beans (fava beans), eggplant or any vegitable in cheese sauce. Chicken liver, herring, smoked or pickled

  16. [Hormone content of the blood plasma of rats after a flight on the Kosmos-1129 biosatellite].

    Science.gov (United States)

    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.

  17. Adrenocortical status in infants and children with sepsis and septic shock

    OpenAIRE

    Hanaa I. Rady; Yasmin S. Aly; Mona Hafez; Bazaraa, Hafez M

    2014-01-01

    Background: The benefit from corticosteroids remains controversial in sepsis and septic shock and the presence of adrenal insufficiency (AI) has been proposed to justify steroid use. Aim: To determine adrenal state and its relation with outcome in critical children admitted with sepsis to PICU of Cairo University, Children Hospital. Methods: Thirty cases with sepsis and septic shock were studied. Cortisol levels (CL) were estimated at baseline and after high-dose short ACTH stimulation ...

  18. A comparison of adrenal gland function in lactating dairy cows with or without ovarian follicular cysts.

    Science.gov (United States)

    Silvia, William J; McGinnis, Angela S; Hatler, T Ben

    2005-03-01

    Two experiments were conducted to determine if adrenal secretion of steroids differed between cows that formed ovarian follicular cysts and normal cycling cows. In experiment 1, lactating Jersey and Holstein cows were diagnosed as having ovarian follicular cysts (follicle diameter >or=20 mm) by rectal palpation. Following diagnosis, ovaries were examined by transrectal ultrasonography three times weekly to detect subsequent ovulation (n=8) or new cyst formation (n=9). Venous blood samples were collected daily to quantify circulating concentrations of cortisol and progesterone. The average concentration of cortisol during the 10-day period prior to ovulation was not different from the concentration prior to the formation of a new cyst. In experiment 2, secretion of cortisol and progesterone was examined in cows with ovarian follicular cysts (n=4) and cyclic, control cows in the follicular phase of the estrous cycle (n=4). An adrenocorticotropic hormone (ACTH) challenge was administered to cystic cows 4-7 days after new cyst formation and to cyclic cows in the follicular phase of the cycle (36 h after induction of luteolysis). Jugular venous blood samples were collected at -60, -30, 0, +10, +20, +30, +60, +90, +120, +180, +240, +300 and +360 minutes relative to ACTH administration. A rapid increase in both cortisol and progesterone was observed immediately following administration of ACTH in each treatment group. Peak concentrations of both steroids were achieved within 60 minutes after administration of ACTH. Concentrations of cortisol and progesterone did not differ between cystic and cyclic cows. In summary, no differences in adrenal function were detected between normal cycling cows and cows with ovarian follicular cysts.

  19. Role of Protein Phosphorylation and Tyrosine Phosphatases in the Adrenal Regulation of Steroid Synthesis and Mitochondrial Function

    Science.gov (United States)

    Paz, Cristina; Cornejo Maciel, Fabiana; Gorostizaga, Alejandra; Castillo, Ana F.; Mori Sequeiros García, M. Mercedes; Maloberti, Paula M.; Orlando, Ulises D.; Mele, Pablo G.; Poderoso, Cecilia; Podesta, Ernesto J.

    2016-01-01

    In adrenocortical cells, adrenocorticotropin (ACTH) promotes the activation of several protein kinases. The action of these kinases is linked to steroid production, mainly through steroidogenic acute regulatory protein (StAR), whose expression and activity are dependent on protein phosphorylation events at genomic and non-genomic levels. Hormone-dependent mitochondrial dynamics and cell proliferation are functions also associated with protein kinases. On the other hand, protein tyrosine dephosphorylation is an additional component of the ACTH signaling pathway, which involves the “classical” protein tyrosine phosphatases (PTPs), such as Src homology domain (SH) 2-containing PTP (SHP2c), and members of the MAP kinase phosphatase (MKP) family, such as MKP-1. PTPs are rapidly activated by posttranslational mechanisms and participate in hormone-stimulated steroid production. In this process, the SHP2 tyrosine phosphatase plays a crucial role in a mechanism that includes an acyl-CoA synthetase-4 (Acsl4), arachidonic acid (AA) release and StAR induction. In contrast, MKPs in steroidogenic cells have a role in the turn-off of the hormonal signal in ERK-dependent processes such as steroid synthesis and, perhaps, cell proliferation. This review analyzes the participation of these tyrosine phosphates in the ACTH signaling pathway and the action of kinases and phosphatases in the regulation of mitochondrial dynamics and steroid production. In addition, the participation of kinases and phosphatases in the signal cascade triggered by different stimuli in other steroidogenic tissues is also compared to adrenocortical cell/ACTH and discussed. PMID:27375556

  20. The value of prolactin in inferior petrosal sinus sampling with desmopressin stimulation in Cushing's disease.

    Science.gov (United States)

    Qiao, Xiaona; Ye, Hongying; Zhang, Xiaolong; Zhao, Weiwei; Zhang, Shuo; Lu, Bin; Wang, Xuanchun; Zhang, Zhaoyun; Wu, Xi; He, Min; Zhao, Xiaolong; Li, Shiqi; Zhou, Linuo; Yang, Yehong; Hu, Renming; Li, Yiming

    2015-03-01

    Prolactin may reduce false-negative results in diagnosing Cushing's disease (CD) during inferior petrosal sinus sampling (IPSS). Prolactin normalization could improve the accuracy of IPSS in predicting adenoma lateralization in CD. However, none of the previous studies had involved the use of desmopressin during IPSS. Our objective was to examine the utility of prolactin measurement during IPSS with desmopressin stimulation. We conducted a retrospective analysis of 40 patients (including 31 females) with ACTH-dependent Cushing's syndrome who underwent IPSS between 2010 and 2013. Thirty-eight CD patients were partitioned into true positive (n = 35) and false negative (n = 3). The proportion of improper IPSS venous sampling defined by corresponding IPS:P (inferior petrosal sinus to peripheral) prolactin ratio prolactin-normalized ACTH IPS:P ratio >0.8 cutoff could increase the sensitivity of IPSS to 38/38 (100 %). Among the 31 patients with histopathologically proven adenoma localization, correct prediction of adenoma lateralization was obtained in 14/31 (45 %) patients by a peak intersinus ACTH gradient of ≥1.4 in baseline and was not improved by desmopressin stimulation. Left-right intersinus gradients of unilateral prolactin-adjusted ACTH IPS:P ratios could increase the correct prediction of adenoma lateralization to 20/31 (65 %) in baseline and 24/31 (77 %) (P = 0.006) after desmopressin stimulation, respectively. Prolactin is helpful to adjust negative results of IPSS with desmopressin stimulation. It may improve the accuracy in predicting adenoma lateralization in CD as well.

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

    Science.gov (United States)

    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 flunixin meglumine (P ≥ 0.14) or any other interactions. Cortisol concentrations increased (P 0.35) with ACTH, but was affected (P 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 Flunixin meglumine treatment suppressed serum PGFM concentrations in control and ACTH-treated cows.

  2. Stress and PTSD Mechanisms as Targets for Pharmacotherapy of Alcohol Abuse, Addiction, and Relapse

    Science.gov (United States)

    2015-10-01

    DST-ACTH whereas SCS and HD:CAS scores showed a negative correlation with baseline cortisol in hypersexual patients. The diagnosis of hypersexual...compared with subse- quent alcohol intake or alcohol preference by Pearson Product Moment Correlation Analysis. The pre-IAA startle response to 58...intake and increased alcohol preference was highly correlated with acoustic startle amplitude previously determined before the initial access to alcohol

  3. 岩下窦取血在Cushing综合征中的诊断价值

    Institute of Scientific and Technical Information of China (English)

    杜培洁; 余勤; 秦贵军; 董义光

    2010-01-01

    @@ 促肾上腺皮质激素(ACTH)依赖性Cushing综合征(Cushing's syndrome,CS)是指下丘脑-垂体病变(包括肿瘤)或垂体以外某些肿瘤组织分泌过量的ACTH或促肾上腺皮质激素释放激素(CRH),导致双侧肾上腺皮质增生并分泌过量皮质醇.

  4. Annual Review of Chronopharmacology. Volume 7. Biological Rhythms and Medications. Proceedings of the Conference of Chronopharmacology Held in Nice, France on 12-15 March 1990

    Science.gov (United States)

    1990-01-01

    Control incubations were performed by omission )f the homogenates. The reaction was terminated by the addition of 100 pLl of cold 2% bovine serum...testiculaire a 1’ACTH chez l’homme adult samn. Ann Endocrinol. (Paris) 41, 59-60. Midgley, A.R., Jr. (1967) Radicimmunoassay of human follicle... reproduction . In: Animal Models for Research on Contraception and Fertility. pp, 31 - 45. N. Alexander (Ed). Harper & Row, New York. Meier, A, H,, John T. M

  5. Cortisol, insulin and leptin during space flight and bed rest

    Science.gov (United States)

    Stein, T. P.; Schluter, M. D.; Leskiw, M. J.

    1999-01-01

    Most ground based models for studying muscle atrophy and bone loss show reasonable fidelity to the space flight situation. However there are some differences. Investigation of the reasons for these differences can provide useful information about humans during space flight and aid in the refinement of ground based models. This report discusses three such differences, the relationships between: (i) cortisol and the protein loss, (ii) cortisol and ACTH and (iii) leptin, insulin and food intake.

  6. Birth by caesarian section alters postnatal function of the hypothalamic-pituitary-adrenal axis in young pigs.

    Science.gov (United States)

    Daniel, J A; Keisler, D H; Sterle, J A; Matteri, R L; Carroll, J A

    1999-03-01

    Eight crossbred sows were selected for the present study (n = 4 vaginal delivery and n = 4 Caesarian section [C-section]). Gestation length did not differ between vaginal delivery and C-section pigs (113.6 +/- .1 and 113.2 +/- .3 d, respectively; P > .16). Blood and tissue samples from 38 pigs were collected at birth. All remaining pigs were sustained with vaginal-delivery sows until 2 wk of age (n = 39). At 2 wk of age, remaining pigs were catheterized for blood sample collection to assess pituitary-adrenal responsiveness to an injection of corticotropin-releasing hormone (CRH; 10 microg/kg). Blood samples were collected at -30, -15, 0, 5, 10, 20, 40, 60, and 90 min; pigs received CRH or saline at time 0. Pigs were killed and tissue samples were collected immediately following the last blood sample. Serum concentrations of ACTH and cortisol (CS) were measured. Total RNA was isolated from the pituitary and adrenal glands to evaluate gene expression for mRNA specific for pro-opiomelanocortin (POMC) and for the ACTH receptor. Centrifuged clot:blood ratio was reduced in the C-section pigs at birth (P pigs. Basal serum concentration of ACTH was greater in C-section than in vaginally delivered pigs at birth (P = .01) but did not differ at 2 wk of age (P = .42). Basal serum concentration of CS was not different at birth (P = .86) but was greater in C-section pigs than in vaginally delivered pigs at 2 wk of age (P .99) between the two groups of pigs following the CRH challenge. However, serum concentration of CS was greater (P pigs following the CRH challenge. Expression of ACTH receptor mRNA tended to be greater in C-section pigs at birth (P .73); however, there was a developmental increase (P pigs.

  7. Apoplejía en metástasis hipofisiaria de carcinoma de células renales: Caso clínico con siete años de seguimiento

    OpenAIRE

    Quevedo L,Iván; Rodríguez Portale,José A; Rosenberg G,Helmar; Mery S,Jorge

    2000-01-01

    We report a man in whom a 15 cm. renal tumor was excised at the age of 49. The pathological examination showed a clear cell carcinoma. Five years later, he presented with headache, vomiting and unilateral palpebral ptosis. Imaging studies showed a sellar tumor with pituitary apoplexy. The tumor was excised and the pathological study disclosed a clear cell tumor, positive for vimentin, cytokeratins AE1 and AE3 and immunohistochemically negative for LH, TSH, ACTH and GH. Considering the similar...

  8. Interleukin 1 (IL-1) type I receptors mediate activation of rat hypothalamus-pituitary-adrenal axis and interleukin 6 production as shown by receptor type selective deletion mutants of IL-1beta.

    Science.gov (United States)

    Van Dam, A M; Malinowsky, D; Lenczowski, M J; Bartfai, T; Tilders, F J

    1998-06-01

    The cytokine interleukin 1 (IL-1) plays an important role in the activation of the hypothalamus-pituary-adrenal (HPA)-axis and interleukin 6 (IL-6) production during infection or inflammation. Which of the interleukin-1 receptor types mediates these effects is not known. To investigate this issue a pharmacological approach was chosen by using recently developed IL-1 receptor type selective ligands. Rats were given one of various doses of recombinant human IL-1beta (rhIL-1beta; 1 and 10 microg/kg) and of several IL-1beta mutants (DeltaSND, DeltaQGE and DeltaI; 1, 10 and 100 microg/kg), that differ in their affinities for the IL-1 type I receptor but have similar affinities for the IL-1 type II receptor. One hour after intravenous administration of rhIL-1beta or IL-1beta mutants, plasma levels of ACTH, corticosterone (cort) and IL-6 were measured. Doses of 1 and 10 microg/kg rhIL-1beta markedly elevated plasma levels of ACTH, cort and IL-6. However, 10-100-fold higher doses of IL-1beta mutants DeltaSND and DeltaQGE and at least 100-fold higher doses of DeltaI have to be administered to increase plasma levels of ACTH, cort and IL-6. The potency differences correlate with their respective affinity for the type I receptor but not with that of the IL-1 type II receptor. It is concluded that IL-1beta induced ACTH, cort and IL-6 production is mediated by interleukin 1 type I receptors.

  9. Deconvolution of Serum Cortisol Levels by Using Compressed Sensing

    OpenAIRE

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

    2014-01-01

    The pulsatile release of cortisol from the adrenal glands is controlled by a hierarchical system that involves corticotropin releasing hormone (CRH) from the hypothalamus, adrenocorticotropin hormone (ACTH) from the pituitary, and cortisol from the adrenal glands. Determining the number, timing, and amplitude of the cortisol secretory events and recovering the infusion and clearance rates from serial measurements of serum cortisol levels is a challenging problem. Despite many years of work on...

  10. Reversible posterior encephalopathy syndrome associated with micronodular adrenocortical disease and Cushing syndrome

    OpenAIRE

    Lodish, Maya; Patronas, Nicholas J.; Stratakis, Constantine A.

    2009-01-01

    We report the case of a 6-year-old female with ACTH-independent Cushing syndrome secondary to bilateral adrenal nodular hyperplasia, who presented with hypertension and seizures, and was found have MRI changes consistent with posterior reversible encephalopathy syndrome (PRES). The patient received anti-hypertensive medication and a bilateral adrenalectomy was performed. One month later, resolution of her brain MRI changes were seen. This is the first case described in the literature of a pat...

  11. Effects of turning duration during incubation on embryo growth, utilization of albumen, and stress regulation.

    Science.gov (United States)

    Tona, K; Onagbesan, O; Bruggeman, V; Mertens, K; Decuypere, E

    2005-02-01

    Eggs from Cobb broiler breeders were incubated for 18 d. Eggs were not turned (T0) or were turned until 9 (T9), 12 (T12), 15 (T15), or 18 (T18) d. First, the effects of turning on embryo and albumen weights were studied. Samples of eggs were opened at d 9, 12, 15, and 18 for embryo and albumen weighing. The results show that embryos from unturned eggs had lower weights and higher remaining albumen weights than those from turned eggs. At d 18, albumen utilization was completed in the T12, T15, and T18 groups only. Also, further turning until d 15 and 18 increased embryo weights. The responsiveness of the embryo after adrenocorticotropic hormone (ACTH) injection was studied to test stress control in embryos. Blood samples were collected from embryos at 60 and 150 min after injection at d 12, 15, and 18 and were analyzed for corticosterone concentrations. The results showed that basal corticosterone levels increased with embryo age. At 60 min after ACTH injection, corticosterone levels were lower at d 12 than at d 15 and 18. At 150 min after ACTH injection, corticosterone levels followed different trends according to incubation stage and turning duration. The highest basal corticosterone levels were obtained with the T15 group at d 15 and 18. Also at d 18, corticosterone levels in the T15 group were the highest at 150 min after ACTH injection. We concluded that egg turning was required during incubation until d 12, at least, and should not be stopped until after d 15.

  12. Adrenal insufficiency.

    Science.gov (United States)

    Li-Ng, Melissa; Kennedy, Laurence

    2012-10-01

    Adrenocortical insufficiency may arise through primary failure of the adrenal glands or due to lack of ACTH stimulation as a result of pituitary or hypothalamic dysfunction. Prolonged administration of exogenous steroids will suppress the hypothalamic-pituitary-adrenal axis, and hence cortisol secretion. We review briefly the causes, investigation, and treatment of adrenal insufficiency, and highlight aspects of particular relevance to patients with adrenal tumors.

  13. Variability of Hormonal Stress Markers Collected from a Managed Dolphin Population

    Science.gov (United States)

    2011-09-30

    in blubber potentially mean that increased plasma cortisol after administration of ACTH treatment may not elevate plasma cortisol for a sufficient...five bottlenose dolphins. Since abrupt cessation of cortisol treatment has been observed to cause side-effects, dolphin subjects will be weaned off...by stress, which can lead to conditions of both hypo- and hyperthyroidism . Persistent elevated or diminished levels of these hormones are known to

  14. Adrenocortical reserves in hyperthyroidism.

    Science.gov (United States)

    Agbaht, Kemal; Gullu, Sevim

    2014-02-01

    Explicit data regarding the changes in adrenocortical reserves during hyperthyroidism do not exist. We aimed to document the capability (response) of adrenal gland to secrete cortisol and DHEA-S during hyperthyroidism compared to euthyroidism, and to describe factors associated with these responses. A standard-dose (0.25 mg/i.v.) ACTH stimulation test was performed to the same patients before hyperthyroidism treatment, and after attainment of euthyroidism. Baseline cortisol (Cor(0)), DHEA-S (DHEA-S(0)), cortisol binding globulin (CBG), ACTH, calculated free cortisol (by Coolen's equation = CFC), free cortisol index (FCI), 60-min cortisol (Cor(60)), and DHEA-S (DHEA-S(60)), delta cortisol (ΔCor), delta DHEA-S (ΔDHEA-S) responses were evaluated. Forty-one patients [22 females, 49.5 ± 15.2 years old, 32 Graves disease, nine toxic nodular goiter] had similar Cor(0), DHEA-S(0), CFC, FCI, and DHEA-S(60) in hyperthyroid and euthyroid states. Cor(60), ΔCor, and ΔDHEA-S were lower in hyperthyroidism. In four (10 %) patients the peak ACTH-stimulated cortisol values were lower than 18 μg/dL. When the test repeated after attainment of euthyroidism, all of the patients had normal cortisol response. Regression analysis demonstrated an independent association of Cor(60) with free T3 in hyperthyroidism. However, the predictors of CFC, FCI, and DHEA-S levels were serum creatinine levels in hyperthyroidism, and both creatinine and transaminase levels in euthyroidism. ACTH-stimulated peak cortisol, delta cortisol, and delta DHEA-S levels are decreased during hyperthyroidism, probably due to increased turnover. Since about 10 % of the subjects with hyperthyroidism are at risk for adrenal insufficiency, clinicians dealing with Graves' disease should be alert to the possibility of adrenal insufficiency during hyperthyroid stage.

  15. Microinjection of muscimol into the periaqueductal gray suppresses cardiovascular and neuroendocrine response to air jet stress in conscious rats.

    Science.gov (United States)

    de Menezes, Rodrigo C A; Zaretsky, Dmitry V; Sarkar, Sumit; Fontes, Marco A P; Dimicco, Joseph A

    2008-09-01

    Microinjection of the neuronal inhibitor muscimol into the dorsomedial hypothalamus (DMH) suppresses increases in heart rate (HR), mean arterial pressure (MAP), and circulating levels of adrenocorticotropic hormone (ACTH) evoked in air jet stress in conscious rats. Similar injection of muscimol into the caudal region of the lateral/dorsolateral periaqueductal gray (l/dlPAG) reduces autonomic responses evoked from the DMH, leading to the suggestion that neurons in the l/dlPAG may represent a descending relay for DMH-induced increases in HR and MAP. Here, we examined the role of neuronal activity in the caudal l/dlPAG on the increases in MAP, HR, and plasma ACTH seen in air jet stress in rats. Microinjection of muscimol into the caudal l/dlPAG reduced stress-induced increases in HR and MAP, while identical injections into sites just dorsal or into the rostral l/dlPAG had no effect. Microinjection of a combination of the glutamate receptor antagonists 2-amino-5-phosphonopentanoate (AP5) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) into the caudal l/dlPAG decreased stress-induced increases in HR alone only at the end of the 20-min stress period but significantly accelerated return to baseline. Surprisingly, microinjection of muscimol into the caudal l/dlPAG also reduced the stress-induced increase in plasma ACTH by 51%. Compared with unstressed control rats, rats exposed to air jet stress exhibited approximately 3 times the number of Fos-positive neurons in the l/dlPAG. These findings suggest that neurons in the l/dlPAG are activated in air jet stress and that this activity contributes to increases in HR, MAP, and plasma ACTH.

  16. Development of a Toxin Knowledge System

    Science.gov (United States)

    1990-11-12

    BRITISH COLUMBIA. 1. NATURAL OCI. NATURAL NEPHROPATHY AND SPONTANEOUS OCCURENCE OF OCCURRENCE AND DIAGNOSIS , CAN J COMP MED 40:12-19...professionals, need exten- sive information on the detection, diagnosis , and treatment of toxin related problems. Military personnel at risk of exposure to...Tucksem MW, Adler SH, Cohen CK, ADMINISTRATION OF ACTH OR CORTICOID TO SOWS IN White KD, Sphon JA: NEGATIVE ION CHEMICAL IONIZATION ADVANCED PREGNANCY

  17. Hypercortisolism as a Potential Concern for Submariners

    Science.gov (United States)

    2010-12-01

    along with other physiological changes such as decreased leptin (-17%), increased glucose (+6%), increased insulin (+22%), increased mean arterial...rats, glucocorticoids have been shown to antagonize leptin (a hormone in the body released by fat cells to reduce food consumption) sensitivity...Sports 2005; 15: 107-112. 79. Schüssler P, Uhr M, Ising M, Weikel JC, Schmid DA, et al. Nocturnal ghrelin , ACTH, GH and cortisol secretion after

  18. Immunolocalization of different neuropeptides in human interthalamic adhaesion indicates its functionality

    OpenAIRE

    Puškaš Laslo; Malobabić Slobodan; Lazić Dijana; Todorović Vera; Aksić Milan; Filipović Branislav

    2014-01-01

    Background/Aim. The interthalamic adhaesion (IA), gray matter connecting both thalami, is absent in about a quarter of human brains. Controversies are present about the nature and functional significance of the human IA. Methods. In six adult human brains we investigated the expression of different neuropeptides: somatosatin (SOM), neuropeptide Y (NPY), ghrelin, neurotensin (NT), adrenocorticotropic hormone (ACTH), substance P (SP) and L-enkephalin (L-Enk) ...

  19. Neuroendocrine, Metabolic and Cardiovascular Responses to Exercise Differ Among Healthy Men

    Science.gov (United States)

    1995-12-20

    adenohypophysis is also useful, providing a more realistic cellular environment for studying ACTH release (Watanabe and Orth, 1988). Therefore, 32 this...dissertation project used hypothalamic explant culture, AtT-20 rat anterior pituitary tumor cells and dispersed primary culture of rat adenohypophysis ...vascular route from hypophysial stalk/neural lobe to adenohypophysis . Am J Physiol 239:R463-R469,1980a. Baertschi, A, Vallet, P, Baumann, J and

  20. Giant Adrenal Myelolipoma Masquerading as Heart Failure

    Directory of Open Access Journals (Sweden)

    Parijat S. Joy

    2014-03-01

    Full Text Available Adrenal myelolipomas are rare benign tumors of the adrenal cortex composed of adipose and hematopoietic cells. They have been postulated to arise from repeated stimulation by stress, inflammation and ACTH oversecretion. Myelolipomas are usually detected incidentally on imaging and do not require any active intervention besides regular follow-up by imaging. However, myelolipomas may insidiously grow to large sizes and cause mass effects and hemorrhage. Timely diagnosis and surgical resection are curative and lifesaving.

  1. Giant adrenal myelolipoma masquerading as heart failure.

    Science.gov (United States)

    Joy, Parijat S; Marak, Creticus P; Nashed, Nadia S; Guddati, Achuta K

    2014-01-01

    Adrenal myelolipomas are rare benign tumors of the adrenal cortex composed of adipose and hematopoietic cells. They have been postulated to arise from repeated stimulation by stress, inflammation and ACTH oversecretion. Myelolipomas are usually detected incidentally on imaging and do not require any active intervention besides regular follow-up by imaging. However, myelolipomas may insidiously grow to large sizes and cause mass effects and hemorrhage. Timely diagnosis and surgical resection are curative and lifesaving.

  2. Effects of pre-experience of social exclusion on hypothalamus-pituitary-adrenal axis and catecholaminergic responsiveness to public speaking stress.

    Directory of Open Access Journals (Sweden)

    Ulrike Weik

    Full Text Available BACKGROUND: Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. METHODS: Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22 or inclusion (SI, n = 21, respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. RESULTS: Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. CONCLUSIONS: We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological

  3. Activity changes of the cat paraventricular hypothalamus during stressor exposure

    DEFF Research Database (Denmark)

    Kristensen, Morten Pilgaard; Rector, David M; Poe, Gina R

    2004-01-01

    Dorso-medial paraventricular hypothalamus (PVH) activity was assessed by light scattering procedures in freely behaving cats during auditory stressor exposure. Acoustic noise (> 95dB) raised plasma ACTH concentrations, somatic muscle tonus, respiratory frequency and cardiac rates; PVH activity...... and nadir. Isolated pixels appeared opposite in activity pattern to overall changes. We suggest that transient activity increases represent initial PVH neural stress responses, and that subsequent profound declines result from neural inhibitory feedback....

  4. Investigation of the Physiological Responses of Belugas to Stressors to Aid in Assessing the Impact of Environmental and Anthropogenic Challenges on Health

    Science.gov (United States)

    2013-12-19

    However, all belugas could establish visual and auditory contact with each other. Blood samples had been collected and archived for a subset of the...Connecticut (UCONN), Department of Marine Biosciences will contribute to development of an assay for measuring stress hormones in cetacean blow as well...activity of granulocytes and monocytes were assayed immediately following blood collection. Hormone (cortisol, ACTH, and aldosterone) and cat echo

  5. Successful treatment of a cat with primary hypoadrenocorticism and severe hyponatremia with desoxycorticosterone pivalate (DOCP)

    Science.gov (United States)

    Woolcock, Andrew D.; Ward, Cynthia

    2015-01-01

    A 6-year-old, castrated male Siamese cat was diagnosed with primary hypoadrenocorticism, confirmed by an adrenocorticotopic hormone (ACTH) stimulation test documenting both hypocortisolism and hypoaldosteronism. The cat was successfully treated using a combination of prednisolone and desoxycorticosterone pivalate (DOCP). This case demonstrates that DOCP can be used successfully as mineralocorticoid supplementation in cats with hypoadrenocorticism and may have a longer therapeutic duration than that in dogs. PMID:26538671

  6. Hyperreninaemic hypoaldosteronism in a dog.

    Science.gov (United States)

    Lobetti, R G

    1998-03-01

    A 9-year-old male German shepherd dog was evaluated for clinical and clinico-pathological changes that were suggestive of Addison's disease. On further investigation the basal plasma cortisol concentration was high, a normal cortisol response to ACTH stimulation occurred, plasma renin activity was elevated and low serum aldosterone concentration was present. A diagnosis of hyperreninaemic hypoaldosteronism was made. Replacement fludrocortisone resulted in complete normalisation of the electrolyte and fluid imbalances. Hyperreninaemic hypoaldosteronism has never been reported in the dog.

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

    Science.gov (United States)

    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.

  8. Transformation of a Silent Adrencorticotrophic Pituitary Tumor Into Central Nervous System Melanoma

    Directory of Open Access Journals (Sweden)

    Brandon A. Miller MD, PhD

    2013-06-01

    Full Text Available Silent adrenocorticotrophic pituitary adenomas are nonfunctioning pituitary adenomas that express adrenocorticotrophic hormone (ACTH but do not cause the clinical or laboratory features of hypercortisolemia. Primary central nervous system (CNS melanoma is well documented, but rarely originates in the sellar region or pituitary gland. Here we report transformation of an aggressive silent adrenocorticotrophic pituitary adenoma that transformed into CNS melanoma and review other presentations of pituitary melanoma. A 37-year-old woman initially presented with apoplexy and an invasive nonfunctioning pituitary macroadenoma for which she underwent transphenoidal surgery. The patient underwent 3 subsequent surgeries as the tumor continued to progress. Pathology from the first 3 operations showed pituitary adenoma or carcinoma. Pathology from the final surgery showed melanoma and the magnetic resonance imaging characteristics of the tumor had changed to become consistent with CNS melanoma. Dermatologic and ophthalmologic examinations did not identify cutaneous or ocular melanoma. The patient’s disease progressed despite aggressive surgical, medical and radiologic treatment. To our knowledge, this is the first report demonstrating transformation of a primary pituitary tumor into melanoma. The mechanism of tumor transformation is unclear, but it is possible that a mutation in the original ACTH-producing tumor lead to increased cleavage of pro-opiomelanocortin or ACTH into α-melanocyte-stimulating hormone, which in turn stimulated the expression of microopthalmia transcription factor, leading to melanocytic phenotype transformation.

  9. Mifepristone Accelerates HPA Axis Recovery in Secondary Adrenal Insufficiency.

    Science.gov (United States)

    Cohan, Pejman

    2016-01-01

    Context. Transient secondary adrenal insufficiency (SAI) is an expected complication following successful adenomectomy of ACTH-secreting pituitary adenomas or unilateral adrenalectomy for cortisol-secreting adrenal adenomas. To date, no pharmacological therapy has been shown to hasten recovery of the hypothalamic-pituitary-adrenal (HPA) axis in this clinical scenario. Case Description. A 33-year-old woman underwent uncomplicated unilateral adrenalectomy for a 3.7 cm cortisol-secreting adrenal adenoma. Postoperatively, she developed SAI and was placed on hydrocortisone 15 mg/day, given in divided doses. In the ensuing six years, the patient's HPA axis failed to recover and she remained corticosteroid-dependent. Quarterly biochemical testing (after withholding hydrocortisone for 18 hours) consistently yielded undetectable serum cortisol and subnormal plasma ACTH levels. While she was on hydrocortisone 15 mg/day, mifepristone was initiated and gradually titrated to a maintenance dose of 600 mg/day after 5 months. Rapid recovery of the HPA axis was subsequently noted with ACTH rising into the supranormal range at 4 months followed by a subsequent rise in cortisol levels into the normal range. After 6 months, the dose of hydrocortisone and mifepristone was lowered and both were ultimately stopped after 8 months. The HPA axis remains normal after an additional 16 months of follow-up. Conclusion. Mifepristone successfully restored the HPA axis in a woman with prolonged secondary adrenal insufficiency (SAI) after adrenalectomy for Cushing's syndrome (CS).

  10. A Patient with Postpartum Hypopituitarism (Sheehan's Syndrome Developed Postpartum Autoimmune Thyroiditis (Transient Thyrotoxicosis and Hypothyroidism: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Nobuyuki Takasu

    2011-01-01

    Full Text Available A 36-year-old woman with postpartum hypopituitarism (Sheehan's syndrome: SS developed postpartum autoimmune thyroiditis (PPAT. She delivered a baby by Caesarean section (620 mL blood loss. At 1 month post partum, she developed thyrotoxicosis due to painless thyroiditis (autoimmune destructive thyroiditis. She was positive for antithyroid antibodies. Postpartum and hypoadrenalism-induced exacerbation of autoimmune thyroiditis caused the thyrotoxicosis due to autoimmune destructive thyroiditis. ACTH was undetectable. She had ACTH deficiency and secondary hypoadrenalism. Hydrocortisone was started. At 6 months post partum, she was referred to us with hypothyroidism. Thyroxine was administered. She had thyrotoxicosis at 1-2 months post partum and then hypothyroidism. She was diagnosed with PPAT. She had hypopituitarism, ACTH deficiency (secondary hypoadrenalism, low prolactin with agalactia, and low LH with failure to resume regular menses. She had empty sella on MRI. She was diagnosed with SS. Three cases with SS have been reported to develop PPAT. Postpartum immunological rebounds and hypoadrenalism-induced immunological alterations (or a combination of the two might have been responsible for the PPAT.

  11. A Patient with Postpartum Hypopituitarism (Sheehan's Syndrome) Developed Postpartum Autoimmune Thyroiditis (Transient Thyrotoxicosis and Hypothyroidism): A Case Report and Review of the Literature.

    Science.gov (United States)

    Takasu, Nobuyuki; Nakayama, Yoshirou

    2011-01-01

    A 36-year-old woman with postpartum hypopituitarism (Sheehan's syndrome: SS) developed postpartum autoimmune thyroiditis (PPAT). She delivered a baby by Caesarean section (620 mL blood loss). At 1 month post partum, she developed thyrotoxicosis due to painless thyroiditis (autoimmune destructive thyroiditis). She was positive for antithyroid antibodies. Postpartum and hypoadrenalism-induced exacerbation of autoimmune thyroiditis caused the thyrotoxicosis due to autoimmune destructive thyroiditis. ACTH was undetectable. She had ACTH deficiency and secondary hypoadrenalism. Hydrocortisone was started. At 6 months post partum, she was referred to us with hypothyroidism. Thyroxine was administered. She had thyrotoxicosis at 1-2 months post partum and then hypothyroidism. She was diagnosed with PPAT. She had hypopituitarism, ACTH deficiency (secondary hypoadrenalism), low prolactin with agalactia, and low LH with failure to resume regular menses. She had empty sella on MRI. She was diagnosed with SS. Three cases with SS have been reported to develop PPAT. Postpartum immunological rebounds and hypoadrenalism-induced immunological alterations (or a combination of the two) might have been responsible for the PPAT.

  12. MAO A knockout attenuates adrenocortical response to various kinds of stress.

    Science.gov (United States)

    Popova, Nina K; Maslova, Larissa N; Morosova, Ekaterina A; Bulygina, Veta V; Seif, Isabelle

    2006-02-01

    The effect of a lack of the gene encoding monoamine oxidase A (MAO A) in transgenic Tg 8 mice on the corticosterone response to restraint, cold, water deprivation-induced, or social acute stress as well as chronic variable stress was studied. It was found that Tg 8 mice with genetic MAO A knockout and wild-type C3H/HeJ (C3H) strain showed similar plasma corticosterone resting level. MAO A knockout mice differed from C3H mice by attenuated response to restraint (60 min), cold (4 degrees C, 60 min), and water deprivation (48 h) as well as to a chronic (15 days) variable stress. No difference between Tg 8 and C3H strains in the response to psychosocial stress (encounters for 30 min of six previously isolated mice) has been found. ACTH administration to dexamethasone-pretreated mice produced a similar corticosterone effect in Tg 8 and C3H mice, indicating that the decreased stress response in MAO A-deficient mice was due rather to the central mechanisms regulating stress-induced ACTH release than to adrenocortical responsiveness to ACTH.

  13. The total flavonoids extracted from Xiaobuxin Tang reverse the hyperactivity of hypothalamic-pituitary-adrenal axis in chronically stressed rats

    Institute of Scientific and Technical Information of China (English)

    AN Lei; ZHANG You-zhi

    2008-01-01

    Objective To investigate the effect of XBXT-2 on the activity of hypothalamic-pituitary-adrenal (HPA) axis in chronic mild stress (CMS) model of rats. Methods Using ELISA to test the serum corticos-terone, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) level in CMS rats; Using western blot to determine hippocampal glucocorticoids receptors (GR) expression in CMS rats. Results Co-administration of XBXT-2 (25, 50 mg·kg-1, p. o., 28 days, the effective doses for behavioral responses) significantly decreased the serum corticosterone and ACTH level in CMS rats, while the CRH level was not markedly affected by chronic stress or drugs. Moreover, XBXT-2 significantly increased the GR expression in the hippocampus of CMS rats. The same effects were observed in the positive control drug imipramine ( 10 mg·kg-1 p. o. ). Conclusions The decrease of serum corticosterone and ACTH level, as well as the increase of hippocampal GR expression may be the mechanisms underlying the antidepressant action of XBXT-2, which may associate with HPA axis.

  14. Chronic Exposure to Cadmium Disrupts the Adrenal Gland Activity of the Newt Triturus carnifex (Amphibia, Urodela

    Directory of Open Access Journals (Sweden)

    Flaminia Gay

    2013-01-01

    Full Text Available We intended to verify the safety of the freshwater values established for cadmium by the European Community and the Italian Ministry of Health in drinking water (5 μg/L and sewage waters (20 μg/L. Therefore, we chronically exposed the newt Triturus carnifex to 5 μg/L and 20 μg/L doses of cadmium, respectively, during 3 and 9 months and verified the effects on the adrenal gland. We evaluated the serum concentrations of adrenocorticotropic hormone (ACTH, corticosterone, aldosterone, norepinephrine, and epinephrine. During the 3-month exposure, both doses of cadmium decreased ACTH and corticosterone serum levels and increased aldosterone and epinephrine serum levels. During the 9-month exposure, the 5 μg/L dose decreased ACTH and increased aldosterone and epinephrine serum levels; the 20 μg/L dose decreased norepinephrine and epinephrine serum levels, without affecting the other hormones. It was concluded that (1 chronic exposure to the safety values established for cadmium disrupted the adrenal gland activity and (2 the effects of cadmium were related both to the length of exposure and the dose administered. Moreover, our results suggest probable risks to human health, due to the use of water contaminated by cadmium.

  15. Chronic Exposure to Cadmium Disrupts the Adrenal Gland Activity of the Newt Triturus carnifex (Amphibia, Urodela)

    Science.gov (United States)

    Gay, Flaminia; Laforgia, Vincenza; Caputo, Ivana; Esposito, Carla; Lepretti, Marilena

    2013-01-01

    We intended to verify the safety of the freshwater values established for cadmium by the European Community and the Italian Ministry of Health in drinking water (5 μg/L) and sewage waters (20 μg/L). Therefore, we chronically exposed the newt Triturus carnifex to 5 μg/L and 20 μg/L doses of cadmium, respectively, during 3 and 9 months and verified the effects on the adrenal gland. We evaluated the serum concentrations of adrenocorticotropic hormone (ACTH), corticosterone, aldosterone, norepinephrine, and epinephrine. During the 3-month exposure, both doses of cadmium decreased ACTH and corticosterone serum levels and increased aldosterone and epinephrine serum levels. During the 9-month exposure, the 5 μg/L dose decreased ACTH and increased aldosterone and epinephrine serum levels; the 20 μg/L dose decreased norepinephrine and epinephrine serum levels, without affecting the other hormones. It was concluded that (1) chronic exposure to the safety values established for cadmium disrupted the adrenal gland activity and (2) the effects of cadmium were related both to the length of exposure and the dose administered. Moreover, our results suggest probable risks to human health, due to the use of water contaminated by cadmium. PMID:23971036

  16. Further neuroendocrine evidence of enhanced vasopressin V3 receptor responses in melancholic depression.

    LENUS (Irish Health Repository)

    Dinan, T G

    2012-02-03

    BACKGROUND: In situations of chronic stress vasopressin plays an important role in regulating the hypothalamic-pituitary adrenal axis. The aim of the current study was to investigate the role of anterior pituitary vasopressin V3 receptors in maintaining the hypercortisolism seen in melancholic depression. METHOD: Fourteen patients with major depression and 14 age- and sex-matched healthy comparison subjects were recruited. Desmopressin (ddAVP) 10 microg was given intravenously and ACTH and cortisol release was monitored for 120 min. RESULTS: The mean +\\/- S.E.M. ACTH response in the depressives was 28.4 +\\/- 4.3 ng\\/l and in the healthy subjects was 18.8 +\\/- 4.9 ng\\/l (P = 0.04). The mean +\\/- S.E.M. cortisol response in the depressives was 261.8 +\\/- 46.5 nmol\\/l and in the healthy subjects was 107.3 +\\/- 26.1 nmol\\/l (P < 0.01). CONCLUSIONS: Patients with major depression have augmented ACTH and cortisol responses to desmopressin indicating enhanced V3 responsivity.

  17. Neuroendocrine response to meta-chlorophenylpiperazine and ipsapirone in relation to anxiety and aggression.

    Science.gov (United States)

    Klaassen, Tineke; Riedel, Wim J; van Praag, Herman M; Menheere, Paul P C A; Griez, Eric

    2002-12-15

    The aim of this study was to establish the association of trait anxiety and anger with hormonal responses to acute challenges with two different 5-HT agonists in a mixed group of patients with depressed mood. Fifteen patients and 16 normal controls received single oral doses of 0.5 mg/kg meta-chlorophenylpiperazine (MCPP), a 5-HT(2C) agonist, and 10 mg of ipsapirone, a 5-HT(1A) agonist, according to a double-blind, placebo-controlled, cross-over design. Dutch-adapted versions of the Spielberger Trait-Anxiety Inventory and the Spielberger Trait-Anger Scale administered assessed at study entry. Hormonal responses, expressed as drug-placebo differences, to MCPP and ipsapirone (changes in cortisol, ACTH and prolactin) were measured. Blood levels of MCPP and ipsapirone were also measured. MCPP and ipsapirone elevated cortisol, ACTH and prolactin. In the patient group, there was a significant correlation between trait anxiety and the cortisol response to MCPP. No significant correlations between the ACTH and prolactin responses to MCPP and levels of anxiety/anger were observed in the patients. No significant correlations could be established between levels of anxiety/anger and hormonal responses to ipsapirone. This study provided evidence for an association between measures of anxiety/aggression and the hormonal response to MCPP. Thus, in subjects with depressed mood, high levels of anxiety suggest a higher probability of 5-HT(2C) disturbances.

  18. Progesterone secreting adrenal mass in a cat with clinical signs of hyperadrenocorticism.

    Science.gov (United States)

    Boord, M; Griffin, C

    1999-03-01

    A 7-year-old 7-kg (16-lb) neutered male Himalayan cat had nonpruritic progressive alopecia of 9 months' duration. The cat had hyperglycemia and glucosuria. Physical examination revealed complete alopecia along the abdomen, inguinal area, medial and caudal areas of the thighs, ventral area of the thorax, and axilla. Clinical signs were consistent with endocrine-induced alopecia and hyperadrenocorticism, however, results of diagnostic tests (ACTH stimulation and low-dose dexamethasone suppression) were not supportive of hyperadrenocorticism. Abdominal ultrasonography revealed a mass cranial to the left kidney. Blood samples were obtained before and after ACTH stimulation to measure sex hormone concentrations. Analysis revealed markedly high blood progesterone concentrations before and after ACTH stimulation. An adrenalectomy was performed and histologic examination of the mass revealed a well-differentiated adrenocortical carcinoma. The right adrenal gland could not be viewed during surgery and was assumed to be atrophic. Following surgery, the hyperglycemia and glucosuria resolved. Within 4 months of surgery, the hyperprogesteronemia had resolved, and at 12 months the cat's coat quality appeared normal. Findings suggest that cats with signs of hyperadrenocorticism should be evaluated not only for abnormal cortisol concentrations, but also for sex hormone abnormalities.

  19. Effect of noise pollution on testicular tissue and hormonal assessment in rat.

    Science.gov (United States)

    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.

  20. Flow cytometry analysis of hormone receptors on human peripheral blood mononuclear cells to identify stress-induced neuroendocrine effects

    Science.gov (United States)

    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.

  1. Small Cell Lung Cancer Presenting as Severe Thrombocytopenia and Refractory Hypokalemia

    Directory of Open Access Journals (Sweden)

    Rohan Mandaliya

    2014-01-01

    Full Text Available A 70-year-old female with a history of mild cirrhosis was referred by her primary care provider for a platelet count of 36,000/μL which had dropped from 47,000/μL in a week along with mild pain in extremities. Serum potassium was low (2.9 mEq/L in spite of the patient being recently started on potassium supplement on outpatient for hypokalemia. Initially thrombocytopenia was attributed to cirrhosis. However, platelet counts continued to drop to a nadir of 9000/μL in spite of several platelet transfusions. Hypokalemia was refractory to potassium supplements. Subsequent bone marrow biopsy revealed extensive marrow necrosis with a focus of small cell tumor cells of pulmonary origin. CT scan of the chest showed a spiculated left lung mass. The ACTH level was high, with normal rennin and aldosterone levels. The patient likely had ectopic ACTH syndrome from small cell lung cancer. She died within few days of diagnosis. Severe thrombocytopenia and refractory hypokalemia can rarely be initial presentations of small cell lung cancer. Thrombocytopenia should prompt an evaluation for bone marrow metastases and a search for undiagnosed systemic malignancy. In severe cases of metastases, bone marrow necrosis can be present. Refractory hypokalemia can be the sole presentation of ectopic ACTH production.

  2. Metachronous Bilateral Testicular Leydig-Like Tumors Leading to the Diagnosis of Congenital Adrenal Hyperplasia (Adrenogenital Syndrome

    Directory of Open Access Journals (Sweden)

    Josip Vukina

    2015-01-01

    Full Text Available A 33-year-old male with a history of left testis Leydig cell tumor (LCT, 3-month status after left radical orchiectomy, presented with a rapidly enlarging (0.6 cm to 3.7 cm right testicular mass. He underwent a right radical orchiectomy, sections interpreted as showing a similar Leydig cell-like oncocytic proliferation, with a differential diagnosis including metachronous bilateral LCT and metachronous bilateral testicular tumors associated with congenital adrenal hyperplasia (a.k.a. “testicular adrenal rest tumors” (TARTs and “testicular tumors of the adrenogenital syndrome” (TTAGS. Additional workup demonstrated a markedly elevated serum adrenocorticotropic hormone (ACTH and elevated adrenal precursor steroid levels. He was diagnosed with congenital adrenal hyperplasia, 3β-hydroxysteroid dehydrogenase deficiency (3BHSD type, and started on treatment. Metachronous bilateral testicular masses in adults should prompt consideration of adult presentation of CAH. Since all untreated CAH patients are expected to have elevated serum ACTH, formal exclusion of CAH prior to surgical resection of a testicular Leydig-like proliferation could be accomplished by screening for elevated serum ACTH.

  3. Sex differences in endocrine response to hyperthermia in sauna.

    Science.gov (United States)

    Jezová, D; Kvetnanský, R; Vigas, M

    1994-03-01

    Neuroendocrine response was investigated during and after a single 20 min bath in sauna (80 degrees C) in a group of 8 healthy men and 8 healthy women. In an additional group of 8 young men, the dynamics of plasma ACTH and cortisol levels were studied during a 30 min sauna exposure (90 degrees C). This dynamic study showed a biphasic response of plasma cortisol which decreased during the initial phase of sauna bath (15 min) and increased thereafter, reaching its maximum 15 min after the end of bathing. Maximal increase in plasma ACTH levels occurred 15 min earlier. In the first sauna exposed group the increase in body temperature was the same (about 2 degrees C) in both sexes. Nevertheless, the elevation in plasma ACTH concentration was significantly more pronounced in women than in men. In the plasma collected at the end of sauna bath inside the sauna room, a significant rise in both adrenaline and noradrenaline levels was found. Though the catecholamine responses were similar in both groups, the increase in heart rate during sauna bath was significantly higher in women. Sauna-induced prolactin release was also more pronounced in women compared with men. Thus hyperthermia induced by sauna exposure resulted in a more pronounced neuroendocrine activation in women compared with men. Moreover, it is evident that repeated blood sampling is necessary to reveal the sauna-induced activation of some hormonal systems.

  4. Acute effects of digoxin on plasma aldosterone and cortisol in monkeys.

    Science.gov (United States)

    Kau, Mei-Mei; Kan, Shu-Fen; Wang, Jiing-Rong; Wang, Paulus S; Lau, Ying-Tung; Wang, Shyi-Wu

    2009-01-01

    Digoxin, a cardiac glycoside, is used to increase cardiac contractility via inhibition of Na(+)/K(+)-adenosinetriphosphatase (ATPase) and increase intracellular calcium in congestive heart failure. Inhibitory effects of digoxin have been demonstrated on the biosynthesis of gonadal hormones and adrenal glucocorticoids in rats. However, acute effects of digoxin on levels of adrenal corticosteroid hormones in the primates in vivo are uncertain. Therefore, we test the hypothesis that a single injection of digoxin decreases the secretion of aldosterone and cortisol in monkeys. An intravenous injection of digoxin (1 microg/kg) inhibited basal and adrenocorticotropin (ACTH)- or KCl-stimulated aldosterone release in monkeys. Furthermore, digoxin induced a decrease in ACTH- and KCl-stimulated cortisol release. Administration of digoxin did not alter plasma concentrations of Na(+) and K(+). Ouabain, a selective inhibitor of Na(+)/K(+)-ATPase, did not affect ACTH- or KCl-stimulated aldosterone and cortisol release. These results revealed that injection of digoxin induced an inhibitory effect on aldosterone and cortisol secretion in monkeys. Because ouabain did not affect levels of plasma aldosterone or cortisol, we suggest that (1) the Na(+)/K(+)-ATPase pathway may not be involved in the mechanism of action of digoxin on aldosterone or cortisol secretion in monkeys and/or (2) the Na(+)/K(+)-ATPase is more sensitive to digoxin than to ouabain in monkeys.

  5. Isolated adrenocortical cells of the domestic fowl (Gallus domesticus): steroidogenic and ultrastructural properties.

    Science.gov (United States)

    Carsia, R V; Scanes, C G; Malamed, S

    1985-02-01

    Isolated adrenocortical cells from White Leghorn chickens (Gallus domesticus) were compared to those from rats (Rattus norvegicus). Cells were prepared from collagenase-dispersed adrenal glands of sexually mature male animals. Corticosterone was measured by radioimmunoassay after incubation for 2 h with steroidogenic agents. Of the four ACTH analogues used, three were 6-17 times more potent with rat cells than with fowl cells (potencies were indicated by half-maximal steroidogenic concentrations). However, 9-tryptophan (O-nitrophenylsulfenyl) ACTH was 8 times more potent with fowl cells than with rat cells, thus suggesting that ACTH receptor differences exist between the two cell types. In addition, cAMP analogues were 10 times more potent with rat cells than with fowl cells suggesting that fowl corticosteroidogenesis is less dependent on cAMP than is rat corticosteroidogenesis. At equal cell concentrations, rat cells secreted 20-40 times more corticosterone than did chicken cells when they were maximally stimulated. Although rat cells converted 8 times more pregnenolone to corticosterone than did fowl cells, the half-maximal steroidogenic concentration for pregnenolone-supported corticosterone synthesis was the same for both cell types (about 5 microM). This suggests that fowl cells have lower steroidogenic enzyme content rather than lower steroidogenic enzyme activity. An unusual feature seen in the isolated fowl adrenocortical cells was an abundance of intracellular filaments.

  6. Genetic disorders involving adrenal development.

    Science.gov (United States)

    Lin, Lin; Ferraz-de-Souza, Bruno; Achermann, John C

    2007-01-01

    The past decade has seen significant advances in our understanding of the genetic aetiology of several forms of adrenal failure that present in infancy or childhood. Several of these disorders affect adrenal development and are termed 'adrenal hypoplasia'. These conditions can be broadly divided into: (1) secondary forms of adrenal hypoplasia due to panhypopituitarism (e.g. HESX1, LHX4, SOX3) or abnormalities in ACTH synthesis (TPIT) or processing (e.g. POMC or PC1); (2) adrenal hypoplasia as part of an ACTH resistance syndrome [MC2R/ACTH receptor, MRAP, AAAS (triple A syndrome)], and (3) primary defects in the development of the adrenal gland itself (primary adrenal hypoplasia). Primary adrenal hypoplasia most commonly occurs in an X-linked form due to mutations in the nuclear receptor DAX1 (NR0B1) but can occur in a poorly understood recessive form or as part of the IMAGe (intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia, genitourinary anomalies) syndrome. Defining the molecular basis of these conditions can have significant clinical implications for management, counselling and presymptomatic diagnosis, as well as providing fascinating insight into normal and abnormal mechanisms of adrenal development in humans.

  7. Lack of specific association between panicogenic properties of caffeine and HPA-axis activation. A placebo-controlled study of caffeine challenge in patients with panic disorder.

    Science.gov (United States)

    Masdrakis, Vasilios G; Markianos, Manolis; Oulis, Panagiotis

    2015-09-30

    A subgroup of patients with Panic Disorder (PD) exhibits increased sensitivity to caffeine administration. However, the association between caffeine-induced panic attacks and post-caffeine hypothalamic-pituitary-adrenal (HPA)-axis activation in PD patients remains unclear. In a randomized, double-blind, cross-over experiment, 19 PD patients underwent a 400-mg caffeine-challenge and a placebo-challenge, both administered in the form of instant coffee. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed at both baseline and post-challenge. No patient panicked after placebo-challenge, while nine patients (47.3%) panicked after caffeine-challenge. Placebo administration did not result in any significant change in hormones' plasma levels. Overall, sample's patients demonstrated significant increases in ACTH, cortisol, and DHEAS plasma levels after caffeine administration. However, post-caffeine panickers and non-panickers did not differ with respect to the magnitude of the increases. Our results indicate that in PD patients, caffeine-induced panic attacks are not specifically associated with HPA-axis activation, as this is reflected in post-caffeine increases in ACTH, cortisol and DHEAS plasma levels, suggesting that caffeine-induced panic attacks in PD patients are not specifically mediated by the biological processes underlying fear or stress. More generally, our results add to the evidence that HPA-axis activation is not a specific characteristic of panic.

  8. Overnight suppression of HPA axis after mineraolocorticoid receptor stimulation: A sleep endocrine study.

    Science.gov (United States)

    Demiralay, Cüneyt; Agorastos, Agorastos; Jahn, Holger; Kellner, Michael; Yassouridis, Alexander; Wiedemann, Klaus

    2015-05-30

    Nocturnal hyperactivity of hypothalamic-pituitary-adrenal axis (HPA) indicates decreased feedback inhibition with stress-related conditions such as major depression and sleep disorders. To characterize the role of mineralocorticoid (MR) in regulation of HPA axis activity during nocturnal sleep and involvement in sleep architecture, we investigated sleep endocrine effects of the MR agonist fludrocortisone in healthy men after pretreatment with metyrapone to minimize the impact of endogenous cortisol. Subjects (n=8) were treated on three occasions in a single-blinded design in random order with a) metyrapone, b) fludrocortisone after metyrapone, and c) placebo. Polysomnography was recorded and blood samples were drawn for determination of adrenocorticotropic hormone (ACTH) and cortisol during the entire night. After metyrapone administration ACTH was significantly enhanced, while overall nocturnal cortisol secretion remained largely unchanged. Whereas administration of fludrocortisone induced a significant inhibitory effect on basal ACTH and cortisol secretion, no considerable effects on sleep pattern were detectable. While the involvement of MR in sleep regulation needs further study, endocrine findings underline the role of MR in tonic regulation of HPA axis during nocturnal sleep and demonstrate the ability of fludrocortisone to further suppress HPA axis activity overnight. Additional studies would be required to evaluate endocrine and clinical fludrocortisone effects in depressive patients showing HPA hyperactivity.

  9. Effects of gender and cigarette smoking on reactivity to psychological and pharmacological stress provocation.

    Science.gov (United States)

    Back, Sudie E; Waldrop, Angela E; Saladin, Michael E; Yeatts, Sharon D; Simpson, Annie; McRae, Aimee L; Upadhyaya, Himanshu P; Contini Sisson, Regana; Spratt, Eve G; Allen, Julia; Kreek, Mary Jeanne; Brady, Kathleen T

    2008-06-01

    We examined the influence of gender and smoking status on reactivity in two human laboratory stress paradigms. Participants were 46 (21 men, 25 women) healthy individuals who completed the Trier Social Stress Task (i.e., performed speech and math calculations in front of an audience) and a pharmacological stress provocation (i.e., administration of corticotrophin releasing hormone (CRH)) after an overnight hospital stay. Approximately half (53%) of the participants were smokers. Cortisol, adrenocorticotrophin hormone (ACTH), physiologic measures (heart rate, blood pressure), and subjective stress were assessed at baseline and at several time points post-task. Men demonstrated higher baseline ACTH and blood pressure as compared to women; however, ACTH and blood pressure responses were more pronounced in women. Women smokers evidenced a more blunted cortisol response as compared to non-smoking women, whereas smoking status did not affect the cortisol response in men. Finally, there was a more robust cardiovascular and subjective response to the Trier as compared to the CRH. Although preliminary, the findings suggest that women may be more sensitive than men to the impact of cigarette smoking on cortisol response. In addition, there is some evidence for a more robust neuroendocrine and physiologic response to acute laboratory stress in women as compared to men.

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

    Science.gov (United States)

    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.

  11. Opioid involvement in the perception of pain due to endurance exercise in trained man

    DEFF Research Database (Denmark)

    Paulev, P E; Thorbøll, J E; Nielsen, U

    1989-01-01

    The purpose of this study was to evaluate the role of endogenous opiates in modulating physical performance during dynamic exercise in conscious man. The plasma concentration of beta-endorphin (BEP) and of adrenocorticotropic hormone (ACTH) along with muscle pain (McGuill Pain Questionnaire) were.......v.). The average (SEM) distance reached was 3,198 (45) m in the naloxone test and 3,240 (38) m in the placebo test. The BEP increased significantly during the tests by a factor of 4.1 on naloxone and by 2.8 on placebo (from the normal resting averages of 1.7 and 2.1 pmol/l, respectively). The ACTH also increased...... significantly by a factor of 2.0 on naloxone and 2.5 on placebo (from the normal resting averages of 19.3 and 16.8 pmol/l, respectively). There were no significant differences between the naloxone and the placebo test with respect to the increments of BEP or ACTH by exercise. However, the perception of muscle...

  12. Melanocortins contribute to sequential differentiation and enucleation of human erythroblasts via melanocortin receptors 1, 2 and 5.

    Directory of Open Access Journals (Sweden)

    Eriko Simamura

    Full Text Available In this study, we showed that adrenocorticotropic hormone (ACTH promoted erythroblast differentiation and increased the enucleation ratio of erythroblasts. Because ACTH was contained in hematopoietic medium as contamination, the ratio decreased by the addition of anti-ACTH antibody (Ab. Addition of neutralizing Abs (nAbs for melanocortin receptors (MCRs caused erythroblast accumulation at specific stages, i.e., the addition of anti-MC2R nAb led to erythroblast accumulation at the basophilic stage (baso-E, the addition of anti-MC1R nAb caused accumulation at the polychromatic stage (poly-E, and the addition of anti-MC5R nAb caused accumulation at the orthochromatic stage (ortho-E. During erythroblast differentiation, ERK, STAT5, and AKT were consecutively phosphorylated by erythropoietin (EPO. ERK, STAT5, and AKT phosphorylation was inhibited by blocking MC2R, MC1R, and MC5R, respectively. Finally, the phosphorylation of myosin light chain 2, which is essential for the formation of contractile actomyosin rings, was inhibited by anti-MC5R nAb. Taken together, our study suggests that MC2R and MC1R signals are consecutively required for the regulation of EPO signal transduction in erythroblast differentiation, and that MC5R signal transduction is required to induce enucleation. Thus, melanocortin induces proliferation and differentiation at baso-E, and polarization and formation of an actomyosin contractile ring at ortho-E are required for enucleation.

  13. Recombinant human leptin attenuates stress axis activity in common carp (Cyprinus carpio L.).

    Science.gov (United States)

    Gorissen, Marnix; Bernier, Nicholas J; Manuel, Remy; de Gelder, Stefan; Metz, Juriaan R; Huising, Mark O; Flik, Gert

    2012-08-01

    Proper functioning of the endocrine stress axis requires communication between the stress axis and other regulatory mechanisms. We here describe an intimate interplay between the stress axis and recombinant human leptin (rhLeptin) in a teleostean fish, the common carp Cyprinus carpio. Restraint stress (by netting up to 96h) increased plasma cortisol but did not affect hepatic leptin expression. Perifusion of pituitary glands or head kidneys with rhLeptin revealed direct effects of rhLeptin on both tissues. RhLeptin suppresses basal and CRF-induced ACTH-secretion in a rapid and concentration-dependent manner. The rhLeptin effect persisted for over an hour after administration had been terminated. RhLeptin decreases basal interrenal cortisol secretion in vitro, and by doing so attenuates ACTH-stimulated cortisol production; rhLeptin does not affect interrenal ACTH-sensitivity. Our findings show that the endocrine stress axis activity and leptin are inseparably linked in a teleostean fish, a notion relevant to further our insights in the evolution of leptin physiology in vertebrates.

  14. Analysis of endocrine disruption effect of Roundup® in adrenal gland of male rats

    Directory of Open Access Journals (Sweden)

    Aparamita Pandey

    2015-01-01

    Full Text Available The effect of Roundup® on adrenal gland steroidogenesis and signaling pathway associated with steroid production was investigated. Doses of 10, 50, 100 and 250 mg/kg bw/d Roundup® were administered for two weeks to adult male rats. The 10 mg/kg bw/d dose which reduced circulatory corticosterone levels, but did not change food consumption and body weight, was selected for further study. The expression of cholesterol receptor (low density lipoprotein receptor, de novo cholesterol synthesis enzyme (3-hydroxy-3-methylglutaryl-coenzyme A synthase, hormone-sensitive lipase, steroidogenic acute regulatory protein (StAR mRNA and phosphorylated form was decreased. Adrenocorticotropic hormone receptor (ACTH, melanocortin-2 receptor, expression was not changed but circulatory ACTH levels and adrenal cortex protein kinase A (PKA activity were reduced. Surprisingly, exogenous ACTH treatment rescued steroidogenesis in Roundup®-treated animals. Apoptosis was evident at 250 mg/kg bw/d, but not at 10 mg/kg bw/d dose. These results suggest that Roundup® may be inhibitory to hypothalamic–pituitary axis leading to reduction in cyclic adenosine monophosphate (cAMP/PKA pathway, StAR phosphorylation and corticosterone synthesis in the adrenal tissue.

  15. Development of potent selective competitive-antagonists of the melanocortin type 2 receptor.

    Science.gov (United States)

    Bouw, Elise; Huisman, Martin; Neggers, Sebastian J C M M; Themmen, Axel P N; van der Lely, A J; Delhanty, Patric J D

    2014-08-25

    Cushing's disease, a hypercortisolemic state induced by an ACTH overexpressing pituitary adenoma, causes increased morbidity and mortality. Selective antagonism of the melanocortin type 2 receptor (MC2R) may be a novel treatment modality. Five structurally related peptides with modified HFRW sites but intact putative MC2R binding sites were tested for antagonistic activity at MC1R, MC2R/MRAP, MC3R, MC4R and MC5R. Two of these peptides (GPS1573 and GPS1574) dose-dependently antagonized ACTH-stimulated MC2R activity (IC50s of 66±23 nM and 260±1 nM, respectively). GPS1573 and 1574 suppressed the Rmax but not EC50 of ACTH on MC2R, indicating non-competitive antagonism. These peptides did not antagonize α-MSH stimulation of MC1R and antagonized MC3, 4 and 5R at markedly lower potency. GP1573 and GPS1574 antagonize MC4R with IC50s of 950 nM and 3.7 μM, respectively. In conclusion, two peptide antagonists were developed with selectivity for MC2R, forming a platform for development of a medical treatment for Cushing's disease.

  16. Functional differentiation of the anterior pituitary cells in the fetal pig. An ultrastructural immunocytochemical study.

    Science.gov (United States)

    Dacheux, F

    1984-01-01

    The fetal porcine pituitary was investigated by means of ultrastructural immunocytochemistry (1) to identify the first cells synthesizing the adenohypophyseal hormones, (2) to follow their differentiation during fetal development, and (3) to compare their ultrastructural characteristics with those of mature adult cells. The first ACTH-cells, which produced and stored ACTH, beta-LPH, beta-MSH, and alpha- and beta-endorphin in the same granules, were very numerous at day 34 and displayed a uniform morphology. At day 50 and thereafter, until the end of gestation, the ACTH-cells differed in their appearance probably reflecting various stages of differentiation of one cell type. The GH-cells gained rapidly ultrastructural features comparable to those of mature GH-cells. In contrast, in the case of PRL-cells, which appeared only at the end of the gestation period as immature elements containing very small secretory granules, the morphological maturation seemed to take place only after birth. The first cells synthesizing the glycoprotein hormones (LH alpha, LH beta, FSH and TSH) displayed ultrastructural features of immature cells. At day 50, their ultrastructural organization started to show a different pattern. At the end of gestation, the TSH-cells and the gonadotropic cells displayed the ultrastructural features of mature cells.

  17. The organochlorine o,p'-DDD disrupts the adrenal steroidogenic signaling pathway in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Lacroix, Martin; Hontela, Alice

    2003-08-01

    The mechanisms of action of o,p'-DDD on adrenal steroidogenesis were investigated in vitro in rainbow trout (Oncorhynchus mykiss). Acute exposures to o,p'-DDD inhibited ACTH-stimulated cortisol secretion while cell viability decreased significantly only at the highest concentration tested (200 microM o,p'-DDD). Stimulation of cortisol secretion with a cAMP analogue (dibutyryl-cAMP) was inhibited at a higher concentration than that needed to inhibit ACTH-stimulated cortisol synthesis in cells exposed to o,p'-DDD. Forskolin-stimulated cortisol secretion and cAMP production, and NaF-stimulated cAMP production were inhibited in a concentration-dependent manner by o,p'-DDD. In contrast, basal cortisol secretion was stimulated while basal cAMP production was unaffected by o,p'-DDD. Pregnenolone-stimulated cortisol secretion was enhanced by o,p'-DDD at a physiologically relevant pregnenolone concentration, while o,p'-DDD inhibited cortisol secretion when a pharmacological concentration of pregnenolone was used. Our results suggest that the cAMP generation step is a target in o,p'-DDD-mediated disruption of ACTH-stimulated adrenal steroidogenesis in rainbow trout but that other downstream targets such as steroidogenic enzymes responsible for cortisol synthesis might also be affected.

  18. The impact of acute stress on hormones and cytokines, and how their recovery is affected by music-evoked positive mood.

    Science.gov (United States)

    Koelsch, Stefan; Boehlig, Albrecht; Hohenadel, Maximilian; Nitsche, Ines; Bauer, Katrin; Sack, Ulrich

    2016-03-29

    Stress and recovery from stress significantly affect interactions between the central nervous system, endocrine pathways, and the immune system. However, the influence of acute stress on circulating immune-endocrine mediators in humans is not well known. Using a double-blind, randomized study design, we administered a CO2 stress test to n = 143 participants to identify the effects of acute stress, and recovery from stress, on serum levels of several mediators with immune function (IL-6, TNF-α, leptin, and somatostatin), as well as on noradrenaline, and two hypothalamic-pituitary-adrenal axis hormones (ACTH and cortisol). Moreover, during a 1 h-recovery period, we repeatedly measured these serum parameters, and administered an auditory mood-induction protocol with positive music and a neutral control stimulus. The acute stress elicited increases in noradrenaline, ACTH, cortisol, IL-6, and leptin levels. Noradrenaline and ACTH exhibited the fastest and strongest stress responses, followed by cortisol, IL-6 and leptin. The music intervention was associated with more positive mood, and stronger cortisol responses to the acute stressor in the music group. Our data show that acute (CO2) stress affects endocrine, immune and metabolic functions in humans, and they show that mood plays a causal role in the modulation of responses to acute stress.

  19. Detecting Adreno-Cortical Activity in Gorillas: A Comparison of Faecal Glucocorticoid Measures Using RIA Versus EIA

    Directory of Open Access Journals (Sweden)

    J.B. Nizeyi

    2011-04-01

    Full Text Available The conservation community is concerned that the remnants of highly endangered Mountain gorilla are being exposed to enormous stressors in their habitat but no assay has been validated to monitor stress markers in their fecal medium. Non specific ICN Corticosterone RIA and Munro Cortisol EIA were validated for measurement of free-ranging Mountain gorilla Faecal Glucocorticoids Metabolites (FGM to non-invasively detect effect of environmental stressors on the adrenocortical activity in gorillas. Parallelism and quantitative recovery of FGM showed that the RIA and EIA can reliably measure corticoid metabolites in this medium. High Performance Liquid Chromatography confirmed presence of FGM in faecal extracts. Peak immunoreactive metabolites constituting 35.43% of FGM measured by the RIA co-eluted with maximum corticosterone radioactivity, the EIA measured multiple immunoreactive peak metabolites which were less polar than the cortisol, corticosterone and DOC standard hormones. For Lowland gorilla, peak FGM eluted at fractions 27 and 53 under the 100% Isocratic gradient (San Diago protocol, and 20-80% Methanol gradient (National Zoo protocol respectively; while peak FGM eluted at fraction 8 and 47 in Mountain gorilla under 100% Isocratic and 20-80% Methanol gradients respectively. After injection of Lowland gorilla with long acting Adrenal Cortico-trophic Hormone (ACTH gel (150U Acthar Gel, urinary cortisol increased by 5-fold (p<0.05 within the first 6 h and then decreased to original values by 24 h. FGM were significantly elevated (p<0.05 between 72 and 96 h (RIA and between 48 and 120 h (EIA and there after decreased towards the pre-ACTH levels. Both assays detected a 2-fold increase in FGM 48 h post ACTH. Mean pre-ACTH and post- ACTH FGM amounts measured by RIA were 36 times (p<0.05 more than those measured by the EIA. For field application FGM were measure from three free-ranging Mountain gorilla individuals before and after chasing the

  20. Copeptin - A potential endocrine surrogate marker of CCK-4-induced panic symptoms?

    Science.gov (United States)

    Demiralay, Cüneyt; Agorastos, Agorastos; Yassouridis, Alexander; Jahn, Holger; Wiedemann, Klaus; Kellner, Michael

    2017-02-01

    Intravenous cholecystokinin-tetrapeptide (CCK-4) administration reliably and dose-dependently provokes panic anxiety in man, accompanied by adrenocorticotropic hormone (ACTH) and cortisol release. Preclinical findings suggest that behavioral and endocrine effects of CCK-4 are mediated via corticotropin-releasing hormone (CRH) release. Anxiogenic stimulation of the central CCK-receptors in man was shown to increase as well vasopressin (AVP), which acts synergistically with CRH as pituitary-adrenocortical axis stimulator during stress. Copeptin (CoP), the C-terminal part of pre-pro-AVP, is released in an equimolar ratio to AVP. It is more stable in the circulation and easier to determine than AVP and it was found to closely mirror the production of AVP. So far, CoP secretion has not been characterized during panic provocation. In 30 healthy male human subjects, we repeatedly measured CoP in plasma during a panic challenge and studied its correlation to Acute Panic Inventory (API) ratings and plasma ACTH and cortisol. CoP levels correlated positively with the increase in API ratings (r=0.41, p=0.03), while ACTH or cortisol did not (r=0.08, p=0.68 and r=0.12, p=0.53, respectively). CoP levels correlated also positively with ACTH (r=0.48, p=0.009) and cortisol (r=0.48, p=0.01) concentrations throughout the CCK-4 challenge. As expected, we found a positive correlation between plasma ACTH and cortisol levels (r=0.57, p=0.001). A vasopressinergic activation during CCK-4 induced panic was demonstrated, which was correlated positively to panic symptoms and pituitary-adrenocortical release. Our findings suggest a role of CoP as a potential surrogate marker of CCK-4 panic symptoms. Further studies are needed to replicate our results and to further clarify the role of CoP as a stress-sensitive hormone in different panic paradigms as well as in panic patients.

  1. Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout

    Energy Technology Data Exchange (ETDEWEB)

    Sandhu, Navdeep [Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada); Vijayan, Mathilakath M., E-mail: mvijayan@uwaterloo.ca [Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada)

    2011-05-15

    Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium targets genes encoding proteins critical for corticosteroid biosynthesis, including melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc), in rainbow trout (Oncorhynchus mykiss). To test this, head kidney slices (containing the interrenal tissues) were incubated in vitro with cadmium chloride (0, 10, 100 and 1000 nM) for 4 h either in the presence or absence of ACTH (0.5 IU/mL). In the unstimulated head kidney slices, cadmium exposure did not affect basal cortisol secretion and the mRNA levels of MC2R and P450scc, while StAR gene expression was significantly reduced. Cadmium exposure significantly suppressed ACTH-stimulated cortisol production in a dose-related fashion. This cadmium-mediated suppression in corticosteroidogenesis corresponded with a significant reduction in MC2R, StAR and P450scc mRNA levels in trout head kidney slices. The inhibition of ACTH-stimulated cortisol production and suppression of genes involved in corticosteroidogenesis by cadmium were completely abolished in the presence of 8-Bromo-cAMP (a cAMP analog). Overall, cadmium disrupts the expression of genes critical for corticosteroid biosynthesis in rainbow trout head kidney slices. However, the rescue of cortisol production as well as StAR and P450scc gene expressions by cAMP analog suggests that cadmium impact occurs upstream of cAMP production. We propose that MC2R signaling, the primary step in ACTH-induced cortocosteroidogenesis, is a key target for cadmium-mediated disruption of

  2. The adrenal gland and the patient with pulmonary tuberculosis infected with human immunodeficiency virus

    Directory of Open Access Journals (Sweden)

    Ifedayo Adeola Odeniyi

    2017-01-01

    Full Text Available Background: The adrenal gland is not spared from the involvement by tuberculosis. One of the recognized causes of adrenal insufficiency (AI is tuberculosis. AI, mostly at the subclinical level, is common in persons with pulmonary tuberculosis (PTB infection, occurring in about 23% of patients. Coinfection with PTB and human immunodeficiency virus (HIV may compromise adrenocortical function and produce significant adrenocortical insufficiency. Objective: To determine if coinfection with tuberculosis and HIV have a compound effect on adrenocortical function in persons with HIV and PTB coinfection. Materials and Methods: Persons with sputum-positive PTB, treatment naive, who met our inclusion criteria, were selected. All the recruited patients were screened for HIV and those positive for HIV infection had confirmatory test. A baseline blood samples for cortisol, fasting plasma glucose, full blood count, and electrolytes were collected between 8.00 h and 9.00 h immediately before administration of adrenocorticotropic hormone (ACTH. The persons received an intravenous bolus injection of 1 μg ACTH (Alliance Pharmaceuticals Ltd., Chippenham, Wiltshire SN15 2BB and blood sample was drawn for cortisol level at 30 min. Results: Forty-four people with PTB infection and forty people with PTB and HIV coinfection met the inclusion criteria of the study. The adrenal response to 1 μg ACTH stimulation in participants with PTB and PTB and HIV coinfection showed that the mean basal cortisol level in the 2 groups was not statistically significant; however, 30-min post-ACTH stimulation cortisol level was 630.84 ± 372.17 and 980.36 ± 344.82 nmol/L (P < 0.001 and increment was 367.79 ± 334.87 and 740.77 ± 317.97 nmol/L (P < 0.001, respectively. Fourteen persons (31.8% with PTB has subnormal adrenal response to ACTH stimulation while only 2 (5% persons with PTB and HIV coinfection has subnormal response. Conclusion: AI, at subclinical level, was less frequent in

  3. What factors drive prolactin and corticosterone responses to stress in a long-lived bird species (snow petrel Pagodroma nivea)?

    Science.gov (United States)

    Angelier, Frédéric; Moe, Børge; Blanc, Samuel; Chastel, Olivier

    2009-01-01

    Life-history theory predicts that individuals should adapt their parental investment to the costs and benefits of the current reproductive effort. This could be achieved by modulating the hormonal stress response, which may shift energy investment away from reproduction and redirect it toward survival. In birds, this stress response consists of a release of corticosterone that may be accompanied by a decrease in circulating prolactin, a hormone involved in the regulation of parental care. We lack data on the modulation of the prolactin stress response. In this study, we tested the hypothesis that individuals should modulate their prolactin stress response according to the fitness value of the current reproductive effort relative to the fitness value of future reproduction. Specifically, we examined the influence of breeding status (failed breeders vs. incubating birds) and body condition on prolactin and corticosterone stress responses in a long-lived species, the snow petrel Pagodroma nivea. When facing stressors, incubating birds had higher prolactin levels than failed breeders. However, we found no effect of body condition on the prolactin stress response. The corticosterone stress response was modulated according to body condition but was not affected by breeding status. We also performed an experiment using injections of adrenocorticotropic hormone (ACTH) and found that the modulation of the corticosterone stress response was probably associated with a reduction in ACTH release by the pituitary and a decrease in adrenal sensitivity to ACTH. In addition, we examined whether prolactin and corticosterone secretion were functionally linked. We found that these two hormonal stress responses were not correlated. Moreover, injection of ACTH did not affect prolactin levels, demonstrating that short-term variations in prolactin levels are not governed directly or indirectly by ACTH release. Thus, we suggest that the corticosterone and prolactin responses to short

  4. 二氧化碳结合力/血钾值在库欣综合征病因诊断中的价值探讨%Carbon dioxide combining power/potassium ratio in etiological diagnosis of Cushing's syndrome

    Institute of Scientific and Technical Information of China (English)

    郭静霞; 窦京涛; 李乐乐; 崔佳; 谷伟军; 杨国庆; 杜锦; 陈康; 臧丽

    2016-01-01

    目的 探讨二氧化碳结合力/血钾值(CO2 CP/K)对库欣综合征病因诊断的价值.方法 回顾性分析1993至2015年解放军总医院内分泌科收治的确诊为库欣综合征、资料齐全的489例患者的临床资料.489例中,促肾上腺皮质激素(ACTH)依赖性库欣综合征243例;非ACTH依赖性库欣综合征246例,其中垂体性库欣综合征(库欣病)214例,异位ACTH综合征29例.应用受试者工作特征曲线对CO2CP/K的诊断价值进行探讨,得出敏感度与特异度均较高的最佳诊断切点.结果 ①与非ACTH依赖性库欣综合征组相比,ACTH依赖性库欣综合征组的血钾水平更低[(3.46±0.77)与(3.69±0.57) mmol/L],CO2 CWK(10.0±5.5与7.6±2.1)更高(t=3.433,P=0.001;t=-3.612,P=0.000).与库欣病组相比,异位ACTH综合征组血钾[(2.47±0.63)与(3.62 f0.67) mmol/L]及血氯水平更低;二氧化碳结合力、碳酸氢根、碱剩余水平及CO2 CP/K(15.6±8.0与7.8±2.4)更高(t=-10.145,P=0.000).2组血钠及pH值差异均无统计学意义(t值分别为1.170和-1.459,均P>0.05).②以ACTH依赖性库欣综合征组为病例组,CO2CWK切点为8.95时灵敏度为0.34、特异度为0.85;以异位ACTH综合征组为病例组CO2CP/K切点为9.09时灵敏度0.89、特异度0.78.结论 CO2 CP/K对ACTH依赖性及ACTH非依赖性库欣综合征诊断价值有限,在一定程度上可以区分库欣病和异位ACTH综合征,便于库欣综合征的病因诊断的初筛.%Objective To evaluate carbon dioxide combining power/potassium ratio (CO2CP/K) in etiological diagnosis of Cushing's syndrome.Methods The clinical data 489 patients with pathohistologically confirmed Cushing's syndrome treated in PLA General Hospital between 1993 and 2015 were retrospectively reviewed.Among 489 patients,there were 246 cases of adrenocorticotropic hormone (ACTH) nondependent Cushing's syndrome and 243 cases of ACTH dependent Cushing's syndrome,including 214 cases of Cushing's disease (CD) and 29 cases of ectopic

  5. 脓毒症患儿血清皮质醇、促肾上腺皮质激素水平的测定及其临床意义%Clinical significance of the determination of serum cortisol and adrenocorticotropic hormone for sepsis in children

    Institute of Scientific and Technical Information of China (English)

    安红; 于哩哩; 徐丽瑾; 毕长柏

    2012-01-01

    目的 动态监测脓毒症、严重脓毒症患儿血清皮质醇、促肾上腺皮质激素( adrenocorticotropic hormone,ACTH)水平的变化,探讨其与临床的关系.方法 以我院2010年9月至2011年1月收治的脓毒症患儿30例为研究对象,分为严重脓毒症组(10例)和脓毒症组(20例).在病程的急性期和恢复期分别检测血清皮质醇及ACTH水平,并与同期住院的10例非脓毒症患儿(对照组)进行对比分析.结果 急性期严重脓毒症组血清皮质醇[( 33.97±6.83) μg/ml]明显高于脓毒症组[(26.30±10.43) μg/ml]和对照组[(19.06±6.91) μg/ml],差异有统计学意义(P<0.01).急性期严重脓毒症组血清ACTH[ (25.47±9.41) pg/ml]明显高于脓毒症组[(15.52±5.85) pg/ml]和对照组[(9.16±3.02) pg/ml],差异有统计学意义(P<0.01).结论 脓毒症患儿发病早期机体存在应激反应,血清皮质醇、ACTH浓度明显升高;血清皮质醇、ACTH浓度升高的水平与病情严重程度有关,血清皮质醇、ACTH水平可作为评估患儿严重程度,判断预后的指标.%Objective To dynamic monitoring the changes of serum cortisol,adrenocorticotropic hormone (ACTH) in children with sepsis and servere sepsis,and to assess it's relationship with clinical features.Methods Thirty children with sepsis were enrolled in this study from Sep 2010 to Jan 2011 in our hospital,and were divided into severe sepsis group (n =10) and sepsis group (n =20).The serum cortisol and ACTH were analysed in acute and recovery period respectively in both two groups,and compared with 10 non-sepsis children as control group.Results In the acute period,the level of serum cortisol in severe sepsis group [ (33.97 ±6.83) μg/ml ] was significantly higher than those in sepsis group [ (26.30 ± 10.43) μg/ml]and control group [ ( 19.06 ± 6.91 ) μg/ml ] ( P < 0.01 ) ; the level of serum ACTH in severe sepsis group [ (25.47 ± 9.41 ) pg/ml ] was significantly higher than those in sepsis group [ ( 15.52

  6. 不同亚型库欣综合征患者肾素-血管紧张素-醛固酮系统变化%The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome

    Institute of Scientific and Technical Information of China (English)

    崔佳; 窦京涛; 杨国庆; 臧丽; 金楠; 陈康; 杜锦; 谷伟军; 王先令

    2015-01-01

    Objective Cushing's syndrome is a clinical condition resulting from chronic exposure to excess glucocorticoid.As a consequence,long-term hypercortisolism contributes significantly to the development of systemic disorders by direct and/or indirect effects.The present study was to analyze the changes of renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome on the standard posture test.Methods We retrospectively reviewed 150 patients with histologically confirmed Cushing's syndrome treated at the PLA General Hospital between 2002 and 2014.Among them,128 patients were diagnosed as adreno-cortico-tropic-hormone (ACTH)-independent Cushing's syndrome,and 22 were ACTH-dependent Cushing's syndrome.All patients were undertaken the posture test.Plasma renin activity (PRA),angiotensin Ⅱ,plasma aldosterone concertration (PAC) levels were measured before and after the test.Results Basal plasma PRA [0.5 (0.2,1.3) μg · L-1 · h-1],angiotensin Ⅱ [(48.9 ± 20.1) ng/L] and PAC [(285.0 ± 128.1) pmol/L] levels were within the normal range in supine position.Compared with the subjects with ACTH-independent Cushing's syndrome,the basal PAC levels were higher in subjects with ACTH-dependent Cushing' s syndrome [(348.0 ± 130.4) pmol/L vs (274.2 ± 125.0) pmol/L,P < 0.05].However,the PAC response in subjects with ACTH-dependent Cushing's syndrome [(49.7 ± 26.4)%] was significantly lower than that in those with ACTH-independent Cushing's syndrome [(81.2 ± 69.3) %] upon upright posture stimulation (P < 0.05).There were no statistical significances in PRA and angiotensin Ⅱ levels between the two groups.The basal PAC and PRA levels were positively correlated with ACTH,whereas PAC response was negatively correlated with ACTH.Conclusions The renin-angiotensin-aldosterone-system activity in subjects with Cushing's syndrome was similar to that in normal control.The basal PAC level and its response to upright posture are differently associated with ACTH

  7. 白芍提取物对嗅球损毁抑郁模型大鼠行为学及下丘脑-垂体-肾上腺轴的影响%Influences of Extract of Peony Radix Alba on Behavior and Hypothalamic-pituitary-adrenocortical Axis in Depressive Rats Model with Damaged Olfactory Bulb

    Institute of Scientific and Technical Information of China (English)

    王景霞; 张建军; 苗春平; 刘妍; 林清; 陈振振

    2011-01-01

    Objective: To investigate the influences of extract from Peony Radix Alba on the behavioral and hypothalamic-pituitary-adrenocortical (HPA) axis changes in rats with damaged olfactory bulb (DOB). Method: The tests of open-field and step-down passive avoidance were used to observe the behaviors of rats.Radioimmunoassay (RIA) was used to analyze the level of corticotropin releasing hormone (CRH) in hypothalamus, adrenocorticotropic hormone (ACTH) in pituitary gland and cortisol (CORT) in serum of rats with DOB. Result: The rats had a characteristic hyperactivity in the test of "open-field" and learning deficits in stepdown passive avoidance ( P < 0. 05 ), and their levels of CRH, ACTH and CORT increased significantly ( P < 0. 05). The extract of Peony Radix Alba at the dose of 70,35 mg·kg-1 corrected the behavioral changes (P < 0. 05 ) and decreased the levels of CRH, ACTH and CORT ( P < 0. 05). Conclusion: The extract of Peony Radix Alba can correct behavioral changes in rats with DOB, and its regulating effect on HPA axis is one of the mechanisms for treating depression.%目的:研究白芍提取物对嗅球损毁抑郁模型大鼠行为学及下丘脑一垂体.肾上腺(HPA)轴的影响.方法:将嗅球损毁大鼠随机分为对照组、模型组、阳性药氟西汀2.5 mg·kg-1组以及白芍提取物70,35,17.5 mg·kg-1组,采用敞箱法、跳台法观察嗅球损毁大鼠的行为变化,间时用放免法分析白芍提取物对嗅球损毁大鼠下丘脑促肾上腺皮质激素释放素(CRH)、垂体促肾上腺皮质激素(ACTH)和血清皮质酮(CORT)含量的影响.结果:大鼠嗅球损毁后敞箱行为出现明显变化,水平运动和垂直运动显著增加,白芍提取物中、高剂量组可显著降低大鼠水平运动和垂直运动的得分;跳台试验中,造模后大鼠训练期和测试期的错误次数显著增加,自芍提取物中、高剂量组能显著降低嗅球损毁大鼠训练期和测试期的触电次数;嗅球损毁大

  8. 睡眠癲痫发作时血清促肾上腺皮质激素和皮质醇的变化%Changes of serum adrenocorticotropic hormone and cortisol levels during sleep seizures

    Institute of Scientific and Technical Information of China (English)

    张守文; 刘玉玺

    2008-01-01

    Objective Measuring the serum concentrations of adrenocorticotropic hormone (ACTH) and cortisol in epileptic seizures during sleep to investigate their link to the EEG changes. Methods Pre-surgical evaluation was performed by video-EEG monitoring using 24 channel recording. Thirty six epilepsy patients could be attributed to two groups: 28 patients had spontaneous seizures, and the other 8 patients whose seizures were induced by bemegride. Another 11 persons with confirmed psychogenic non-epileptic seizures (PNES) served as control group. Blood samples were obtained at five points: wake (08:00a.m.), sleep (00:00a.m.), and shortly before, during and after an epileptic seizure. The serum ACTH and cortisol were measured and analyzed by chemiluminescent immunoassay. Results The levels of ACTH and cortisol in serum underwent significant changes: declining below the average sleep-level shortly before seizures, increasing during seizures, and far above the average wake-level after seizures (P<0.001). Such changes did not occur in the control group (P>0.05). The ACTH and cortisol levels had no significant difference between spontaneous group and bemegride-induced group (P>0.05). Conclusion The serum concentrations of ACTH and cortisol during sleep seizures are linked with pre-ictal and ictal EEG changes in epilepsy patients.%目的 探讨睡眠癫痫患者临床发作时血清促肾上腺皮质激素(adrenocorticotropic hormone, ACTH)和皮质醇的变化及其与脑电波变化之间的联系.方法 采用24导video-EEG对睡眠癫痫患者进行脑电监测,并对其发作前瞬时的EEG进行分析,采用化学发光免疫法在清醒时、睡眠时、发作前瞬间、发作时和发作后的5个时间点测定血清中ACTH和皮质醇的浓度.在36例睡眠癫痫患者中,28例为自然发作,8例为贝美格诱发发作.用11例假性心因性癫痫发作患者作为对照组.结果 睡眠癫痫发作前、中、后血清ACTH和皮质

  9. Characteristics of hormonal profile of children with allergic diseases

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    Shumna T.Ye.

    2013-03-01

    Full Text Available With the purpose to determine features of hormonal type in children with allergic diseases, the levels of adrenocorticotropic hormone (ACTH, thyroid-stimulating hormone (TSH and cortisol were investigated in 110 children in the age from 6 to 17 years. Of them 79 children with allergic diseases (40 children from Zaporozhye and 39 children – from eco¬friendly clean Primorsk and Berdyansk districts of the Zaporozhye area and 31 healthy children (16 children - from Zaporozhye and 15 - with conventionally ecofriendly clean districts of the Zaporozhye area. Levels of hormones (ACTH (pg/ml, TSH (mkIU/ml, cortisol (ng/ml were determined through diagnostic test systems by a standard method in laboratories of the Zaporozhуe state medical university. By research results it is set, that in the conditions of large industrial city Zaporozhуe, forming of allergic pathology in children took place during activating of the hypophysis-adrenal system with the increase of TSH, cortisol, ACTH secretion with a high risk of exhaustion of immunoreactions and persistence of antigens; this was confir¬med by increase of values of their medians in relation to healthy children. In children with allergic diseases, habitants of ecologically favourable Primorsk and Berdyansk districts of the Zaporozhye area, vice versa, lower indexes of medians of ACTH, TSH and cortisol were registered; this testifies to sup¬pression of hypothalamus function and hypophysis system with violation of protective reaction and adaptation mechanisms in response to forming of allergic inflammation. Thus, adjusting of hormonal activity by principle of ne¬gative reverse link in children with allergic diseases was not executed, regardless of place of residence. In addition, indexes of median of ACTH, TSH, cortisol in children with different clinical forms of allergic diseases (bronchial asthma, allergic rhinitis, atopic dermatitis in comparison to healthy ones, testified that for children with

  10. Adiponectin and adiponectin receptor system in the rat adrenal gland: ontogenetic and physiologic regulation, and its involvement in regulating adrenocortical growth and steroidogenesis.

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    Paschke, Lukasz; Zemleduch, Tomasz; Rucinski, Marcin; Ziolkowska, Agnieszka; Szyszka, Marta; Malendowicz, Ludwik K

    2010-09-01

    Adiponectin (ADN) is a regulatory peptide secreted mostly by adipose tissue and acting via two receptors: AdipoR1 and AdipoR2. Our aim was to investigate expression of adiponectin system genes in the rat adrenal gland as well as its ontogenetic and physiological control. Furthermore, we examined the effects of acute and prolonged activation of HPA axis on ADN system in adipose tissue. By means of QPCR, ADN and AdipoR1 expression was demonstrated in rat adrenal cortex both at mRNA and protein levels, while AdipoR2 could only be detected at mRNA levels. ADN expression level was significantly upregulated in a developing and regenerating adrenal cortex. Globular domain of adiponectin at 10(-9) M stimulated corticosterone output and BrdU incorporation by cultured rat adrenocortical cells. Moreover, both acute (ACTH and ether stress) and prolonged (ACTH) adrenal stimulation resulted in lowered ADN levels, while expression of AdipoR1 and AdipoR2 was upregulated by the acute treatment. Depending on its site of origin, visceral (VAT) or subcutaneous (SAT) adipose tissue responded differently to alterations in HPA axis. VAT expression of ADN and its receptors remained almost unchanged by experimental manipulations. In SAT, on the other hand, expression of ADN and AdipoR2 was markedly increased by ACTH treatment and stress, while dexamethasone suppressed ADN and AdipoR1 mRNA levels. The results of this study provide new evidence for direct and indirect interactions between adipokines and HPA axis.

  11. Alcohol administration attenuates hypothalamic-pituitary-adrenal (HPA) activity in healthy men at low genetic risk for alcoholism, but not in high-risk subjects.

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    Mick, Inge; Spring, Konstanze; Uhr, Manfred; Zimmermann, Ulrich S

    2013-09-01

    Acute alcohol challenge studies in rodents and naturalistic observations in drinking alcoholics suggest that alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) system. The literature on respective studies in healthy volunteers is more inconsistent, suggesting differential alcohol effects depending on dosage, recent drinking history, family history of alcoholism and alcohol-induced side effects. These papers and the putative pharmacologic mechanisms underlying alcohol effects on the HPA system are reviewed here and compared with a new study, in which we investigated how secretion of adrenocorticotrophin (ACTH) and cortisol is affected by ingestion of 0.6 g/kg ethanol in 33 young healthy socially drinking males with a paternal history of alcoholism (PHP) versus 30 family history negative (FHN) males. Alcohol and placebo were administered in a 2-day, double-blind, placebo controlled crossover design with randomized administration sequence. After administration of placebo, ACTH and cortisol decreased steadily over 130 minutes. In FHN subjects, secretion of both hormones was even more attenuated after alcohol, resulting in significantly lower levels compared with placebo. In PHP subjects, no alcohol effect on hormone secretion could be detected. The ratio of cortisol to ACTH secretion, each expressed as area under the secretion curve, was significantly increased by alcohol in FHN and PHP participants. These results argue against HPA stimulation being a mechanism that promotes the transition from moderate to dependent drinking. The fact that alcohol-induced HPA suppression was not detected in PHP males is consistent with the general concept that subjects at high risk for alcoholism exhibit less-pronounced alcohol effects.

  12. Activation of PPAR-γ reduces HPA axis activity in diabetic rats by up-regulating PI3K expression.

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    Torres, Rafael Carvalho; Magalhães, Nathalia Santos; E Silva, Patrícia M R; Martins, Marco A; Carvalho, Vinicius F

    2016-10-01

    Increased hypothalamus-pituitary-adrenal axis (HPA) activity in diabetes is strongly associated with several morbidities noted in patients with the disease. We previously demonstrated that hyperactivity of HPA axis under diabetic conditions is associated with up-regulation of adrenocorticotrophic hormone (ACTH) receptors (MC2R) in adrenal and down-regulation of glucocorticoid receptors (GR and MR) in pituitary. This study investigates the role of peroxisome proliferator-activated receptor (PPAR)-γ in HPA axis hyperactivity in diabetic rats. Diabetes was induced by intravenous injection of alloxan into fasted rats. The PPAR-γ agonist rosiglitazone and/or PI3K inhibitor wortmannin were administered daily for 18 consecutive days, starting 3days after diabetes induction. Plasma ACTH and corticosterone were evaluated by radioimmunoassay, while intensities of MC2R, proopiomelanocortin (POMC), GR, MR, PI3K p110α and PPAR-γ were assessed using immunohistochemistry. Rosiglitazone treatment inhibited adrenal hypertrophy and hypercorticoidism observed in diabetic rats. Rosiglitazone also significantly reversed the diabetes-induced increase in the MC2R expression in adrenal cortex. We noted that rosiglitazone reduced the number of corticotroph cells and inhibited both anterior pituitary POMC expression and plasma ACTH levels. Furthermore, rosiglitazone treatment was unable to restore the reduced expression of GR and MR in the anterior pituitary of diabetic rats. Rosiglitazone increased the number of PPAR-γ(+) cells and expression of PI3K p110α in both anterior pituitary and adrenal cortex of diabetic rats. In addition, wortmannin blocked the ability of rosiglitazone to restore corticotroph cell numbers, adrenal hypertrophy and plasma corticosterone levels in diabetic rats. In conclusion, our findings revealed that rosiglitazone down-regulates HPA axis hyperactivity in diabetic rats via a mechanism dependent on PI3K activation in pituitary and adrenal glands.

  13. Loss of melanocortin-4 receptor function attenuates HPA responses to psychological stress.

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    Ryan, Karen K; Mul, Joram D; Clemmensen, Christoffer; Egan, Ann E; Begg, Denovan P; Halcomb, Kristen; Seeley, Randy J; Herman, James P; Ulrich-Lai, Yvonne M

    2014-04-01

    The melanocortin 4 receptor (MC4R), well-known for its role in the regulation of energy balance, is widely expressed in stress-regulatory brain regions, including the paraventricular nucleus of the hypothalamus (PVH) and the medial amygdala (MeA). In agreement with this, MC4R has been implicated in hypothalamic-pituitary-adrenocortical axis (HPA) regulation. The present work investigated the role of chronic Mc4r function to modulate basal HPA axis tone and to facilitate acute HPA responses to psychological stress, using a novel rat model with Mc4r loss-of-function. In this study, adult male rats were placed into 3 groups (n=15/group) according to genotype [wild-type (WT); heterozygous mutant (HET); and homozygous mutant (HOM)]. Basal (pre-stress) plasma adrenocorticotropic hormone (ACTH) and corticosterone were measured in the AM and PM, and the HPA axis response to restraint was assessed in the AM. Rats were perfused at 2h after restraint to assess the effect of loss of MC4R on stress-induced c-Fos immunolabeling in stress-regulatory brain regions. We find that basal (non-stress) AM and PM plasma ACTH and corticosterone showed a normal diurnal rhythm that was not altered according to genotype. Consistent with this, adrenal and thymus weights were unaffected by genotype. However, the plasma ACTH and corticosterone responses to restraint were significantly reduced by loss of MC4R function. Likewise, stress-induced c-Fos immunolabeling in both PVH and MeA was significantly reduced by loss of Mc4r function. These results support the hypothesis that endogenous MC4R signaling contributes to the HPA axis response to stress. Because MC4R plays a critical role in the regulation of energy balance, the present work suggests that it may also serve as an important communication link between brain metabolic and stress systems.

  14. Effect of cortisol on muscle sympathetic nerve activity in Pima Indians and Caucasians.

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    Vozarova, Barbora; Weyer, Christian; Snitker, Soren; Gautier, Jean-Francois; Cizza, Giovanni; Chrousos, George; Ravussin, Eric; Tataranni, P Antonio

    2003-07-01

    The hypothalamo-pituitary-adrenal axis and sympathetic nervous system (SNS) interact to maintain cardiovascular and metabolic homeostasis, especially during stress. Pima Indians have a low SNS activity, which may contribute to both their increased risk of obesity and reduced risk of hypertension. Although glucocorticoids inhibit SNS activity, Pima Indians are not hypercortisolemic compared with Caucasians. This does not exclude the possibility that the SNS is more responsive to an inhibitory effect of cortisol in the former than in the latter group. We measured fasting plasma ACTH and cortisol and muscle SNS activity [muscle sympathetic nervous system activity (MSNA), microneurography] in 58 males [27 Pimas/31 Caucasians]. Seven Pimas and 12 Caucasians were randomized to a double-blind, placebo-controlled, cross-over study to examine the effect of overnight partial chemical adrenalectomy (metyrapone) followed by cortisol replacement (hydrocortisone) on plasma ACTH, cortisol, and MSNA. There were no ethnic differences in fasting plasma ACTH or cortisol, but MSNA adjusted for percent body fat was lower in Pimas than in Caucasians (P fasting cortisol and basal MSNA. Administration of metyrapone did not lead to significant changes in MSNA. In response to a hydrocortisone infusion, MSNA decreased in Pima Indians (P = 0.03) but not in Caucasians (P = 0.7). Our data indicate that the low SNS activity that predisposes Pima Indians to obesity is not due to a tonic inhibitory effect of cortisol. However, an acute release of cortisol is likely to more effectively contain sympathoexcitation during stress in Pima Indians than in Caucasians, which may be an important mechanism of cardioprotection in this Native American population.

  15. The neurochemistry and social flow of singing: bonding and oxytocin.

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    Keeler, Jason R; Roth, Edward A; Neuser, Brittany L; Spitsbergen, John M; Waters, Daniel J M; Vianney, John-Mary

    2015-01-01

    Music is used in healthcare to promote physical and psychological well-being. As clinical applications of music continue to expand, there is a growing need to understand the biological mechanisms by which music influences health. Here we explore the neurochemistry and social flow of group singing. Four participants from a vocal jazz ensemble were conveniently sampled to sing together in two separate performances: pre-composed and improvised. Concentrations of plasma oxytocin and adrenocorticotropic hormone (ACTH) were measured before and after each singing condition to assess levels of social affiliation, engagement and arousal. A validated assessment of flow state was administered after each singing condition to assess participants' absorption in the task. The feasibility of the research methods were assessed and initial neurochemical data was generated on group singing. Mean scores of the flow state scale indicated that participants experienced flow in both the pre-composed (M = 37.06) and improvised singing conditions (M = 34.25), with no significant difference between conditions. ACTH concentrations decreased in both conditions, significantly so in the pre-composed singing condition, which may have contributed to the social flow experience. Mean plasma oxytocin levels increased only in response to improvised singing, with no significant difference between improvised and pre-composed singing conditions observed. The results indicate that group singing reduces stress and arousal, as measured by ACTH, and induces social flow in participants. The effects of pre-composed and improvised group singing on oxytocin are less clear. Higher levels of plasma oxytocin in the improvised condition may perhaps be attributed to the social effects of improvising musically with others. Further research with a larger sample size is warranted.

  16. The Neurochemistry and Social Flow of Singing: Bonding and Oxytocin

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    Jason R. Keeler

    2015-09-01

    Full Text Available Music is used in healthcare to promote physical and psychological well-being. As clinical applications of music continue to expand, there is a growing need to understand the biological mechanisms by which music influences health. Here we explore the neurochemistry and social flow of group singing. 4 participants from a vocal jazz ensemble were conveniently sampled to sing together in two separate performances: pre-composed and improvised. Concentrations of plasma oxytocin and adrenocorticotropic hormone (ACTH were measured before and after each singing condition to assess levels of social affiliation, engagement and arousal. A validated assessment of flow state was administered after each singing condition to assess participants’ absorption in the task. The feasibility of the research methods were assessed and initial neurochemical data was generated on group singing. Mean scores of the flow state scale indicated that participants experienced flow in both the pre-composed (M=37.06 and improvised singing conditions (M=34.25, with no significant difference between conditions. ACTH concentrations decreased in both conditions, significantly so in the pre-composed singing condition, which may have contributed to the social flow experience. Mean plasma oxytocin levels increased only in response to improvised singing, with no significant difference between improvised and pre-composed singing conditions observed. The results indicate that group singing reduces stress and arousal, as measured by ACTH, and induces social flow in participants. The effects of pre-composed and improvised group singing on oxytocin are less clear. Higher levels of plasma oxytocin in the improvised condition may perhaps be attributed to the social effects of improvising musically with others. Further research with a larger sample size is warranted.

  17. Demographic study of pituitary adenomas undergone trans-sphenoidal surgery in Loghman Hakim Hospital, Tehran, Iran 2001–2013

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    Farahnaz Bidari Zerehpoosh

    2015-01-01

    Full Text Available Background: Pituitary adenomas (PAs are abnormal benign tumors that develop in the pituitary gland. This study aimed to assess the prevalence of different types of PAs with an indication for trans-sphenoidal surgery in a well-defined population referred to Loghman Hakim Hospital during 2001–2013. Subjects and Methods: In this retrospective study, the prevalence rate and symptoms associated with pituitary mass and hormone excess in operated patients were investigated. The diagnosis was verified after retrieval of clinical, hormonal, radiological, and pathological data. Demographic data were collected in all cases. Descriptive analysis, t-test, one-way analysis of variance and Fischer exacts test were used. Results: A total of 278 patients with PAs who underwent surgical interventions were evaluated. Most of the patients were aged 40–50 years with an average of 41 ± 14. The most prominent complaint was pressure effect, which was detected in 153 cases (55.2%. At the second place, hormonal disorders were observed in 125 cases (44.8%. Type of pituitary tumors were: Prolactinomas (29.1%, growth hormone (GH-producing tumors (25%, nonfunctioning PAs (28.4%, adrenocorticotropic hormone (ACTH-producing tumors (2.1%, thyroid stimulating hormone (TSH-producing tumors (0.7%, GH/prolactin (13.6%, GH/ACTH (0.3%, and TSH/ACTH (0.3%. Fifty-seven patients presented with recurrent adenomas. Pituitary apoplexy was found in 11 patients. One case of Sheehan syndrome was recorded among these. The correlations between clinical symptoms and patients, age and sex were not significant. Conclusion: The overview of demographic characteristics in Iranian patients with PAs with surgical indication has been discussed in the present investigation. The prevalence of different types of PAs and the most common clinical symptoms have been demonstrated.

  18. Adaptation of the pituitary-adrenal axis to daily repeated forced swim exposure in rats is dependent on the temperature of water.

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    Rabasa, Cristina; Delgado-Morales, Raúl; Gómez-Román, Almudena; Nadal, Roser; Armario, Antonio

    2013-11-01

    Comparison of exposure to certain predominantly emotional stressors reveals a qualitatively similar neuroendocrine response profile as well as a reduction of physiological responses after daily repeated exposure (adaptation). However, particular physical components of the stressor may interfere with adaptation. As defective adaptation to stress can enhance the probability to develop pathologies, we studied in adult male rats (n = 10/group) swimming behavior (struggling, immobility and mild swim) and physiological responses (ACTH, corticosterone and rectal temperature) to daily repeated exposure to forced swim (20 min, 13 d) at 25 or 36 °C (swim25 or swim36). Rats were repeatedly blood-sampled by tail-nick and hormones measured by radioimmunoassay. Some differences were observed between the two swim temperature groups after the first exposure to forced swim: (a) active behaviors were greater in swim25 than swim36 groups; (b) swim25 but not swim36 caused hypothermia; and (c) swim36 elicited the same ACTH response as swim25, but plasma corticosterone concentration was lower for swim36 at 30 min post-swim. After daily repeated exposure, adaptation in ACTH secretion was observed with swim36 already on day 4, whereas with swim25 adaptation was not observed until day 13 and was of lower magnitude. Nevertheless, after repeated exposure to swim25 a partial protection from hypothermia was observed and the two swim conditions resulted in progressive reduction of active behaviors. Thus, daily repeated swim at 25 °C impairs adaptation of the hypothalamic-pituitary-adrenal axis as compared to swim at 36 °C, supporting the hypothesis that certain physical components of predominantly emotional stressors can interfere with the process of adaptation.

  19. Sources of variation in plasma corticosterone and dehydroepiandrosterone in the male northern cardinal (Cardinalis cardinalis): I. Seasonal patterns and effects of stress and adrenocorticotropic hormone.

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    Fokidis, H Bobby

    2016-09-01

    The secretion of steroids from the adrenal gland is a classic endocrine response to perturbations that can affect homeostasis. During an acute stress response, glucocorticoids (GC), such as corticosterone (CORT), prepare the metabolic physiology and cognitive abilities of an animal in a manner that promotes survival during changing conditions. Although GC functions during stress are well established, much less is understood concerning how adrenal androgens, namely dehydroepiandrosterone (DHEA) are influenced by stress. I conducted three field studies (one experimental and two descriptive) aimed at identifying how both CORT and DHEA secretion in free-living male northern cardinals (Cardinalis cardinalis), vary during acute stress; across different circulations (brachial vs. jugular); in response to ACTH challenge; and during the annual cycle. As predicted, restraint stress increased plasma CORT, but unexpectedly DHEA levels decreased, but the latter effect was only seen for blood sampled from the jugular vein, and not the brachial. The difference in DHEA between circulations may result from increased neural uptake of DHEA during stress. Injection with exogenous adrenocorticotropic hormone (ACTH) increased CORT concentrations, but failed to alter DHEA levels, thus suggesting ACTH is not a direct regulator of DHEA. Monthly field sampling revealed distinct seasonal patterns to both initial and restraint stress CORT and DHEA levels with distinct differences in the steroid milieu between breeding and non-breeding seasons. These data suggest that the CORT response to stress remains relatively consistent, but DHEA secretion is largely independent of the response by CORT. Although CORT functions have been well-studied in wild animals, little research exists for the role of DHEA and their variable relationship sets the stage for future experimental research addressing steroid stress responses.

  20. The Renin-Angiotensin-Aldosterone system in patients with depression compared to controls – a sleep endocrine study

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    Künzel Heike

    2003-10-01

    Full Text Available Abstract Background Hypercortisolism as a sign of hypothamamus-pituitary-adrenocortical (HPA axis overactivity and sleep EEG changes are frequently observed in depression. Closely related to the HPA axis is the renin-angiotensin-aldosterone system (RAAS as 1. adrenocorticotropic hormone (ACTH is a common stimulus for cortisol and aldosterone, 2. cortisol release is suppressed by mineralocorticoid receptor (MR agonists 3. angiotensin II (ATII releases CRH and vasopressin from the hypothalamus. Furthermore renin and aldosterone secretion are synchronized to the rapid eyed movement (REM-nonREM cycle. Methods Here we focus on the difference of sleep related activity of the RAAS between depressed patients and healthy controls. We studied the nocturnal plasma concentration of ACTH, cortisol, renin and aldosterone, and sleep EEG in 7 medication free patients with depression (1 male, 6 females, age: (mean +/-SD 53.3 ± 14.4 yr. and 7 age matched controls (2 males, 5 females, age: 54.7 ± 19.5 yr.. After one night of accommodation a polysomnography was performed between 23.00 h and 7.00 h. During examination nights blood samples were taken every 20 min between 23.00 h and 7.00 h. Area under the curve (AUC for the hormones separated for the halves of the night (23.00 h to 3.00 h and 3.00 h to 7.00 h were used for statistical analysis, with analysis of co variance being performed with age as a covariate. Results No differences in ACTH and renin concentrations were found. For cortisol, a trend to an increase was found in the first half of the night in patients compared to controls (p Conclusion Hyperaldosteronism could be a sensitive marker for depression. Further our findings point to an altered renal mineralocorticoid sensitivity in patients with depression.