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Sample records for pituitary adrenal axis

  1. Oxytocin and hypothalamo-pituitary- adrenal axis

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    Berrak Ç. Yeğen

    2010-05-01

    Full Text Available BSTRACT: Upon exposure to different types of stressors, neuroendocrine and behavioral responses that include the activation of the hypothalamus-pituitary-adrenal (HPA axis are given to allow the individuals to cope with stress conditions. It was proven that oxytocin, anonapeptide released from the posterior pituitary, has behavioral and stress-attenuating effects by dampening HPA activity. On the other hand, the neuropeptide was also shown to exert anti-inflammatory effects through the modulation of immune and inflammatory processes in several experimental models of tissue injury. The findings of recent studies suggest that the anti-inflammatory effect of oxytocin depends on its role on HPA axis activity and subsequent release of cortisol. Thus, oxytocin seems to restrain the activity within the HPA-axis, which becomes overactive during many inflammatory processes

  2. Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis

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    Mikkelsen, Jens D; Hay-Schmidt, Anders; Kiss, Alexander

    2004-01-01

    Acute stimulation of the hypothalamo-pituitary-adrenal (HPA) axis by selective serotonin reuptake inhibitors (SSRIs) is mediated by several postsynaptic 5-HT receptor subtypes. Activation of 5-HT(1A) and 5-HT(2A) receptors increases plasma corticosterone levels, and it is likely that these recept...

  3. Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis.

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    Takahiro Teshima

    Full Text Available Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to suppressive negative feedback by glucocorticoids. The abnormal expression of 11beta-hydroxysteroid dehydrogenase (11HSD, which is a cortisol metabolic enzyme, is found in human and murine corticotroph adenomas. Our recent studies demonstrated that canine corticotroph adenomas also have abnormal expression of 11HSD. 11HSD has two isoforms in dogs, 11HSD type1 (HSD11B1, which converts cortisone into active cortisol, and 11HSD type2 (HSD11B2, which converts cortisol into inactive cortisone. It has been suggested that glucocorticoid resistance in corticotroph tumors is related to the overexpression of HSD11B2. Therefore it was our aim to investigate the effects of carbenoxolone (CBX, an 11HSD inhibitor, on the healthy dog's pituitary-adrenal axis. Dogs were administered 50 mg/kg of CBX twice each day for 15 days. During CBX administration, no adverse effects were observed in any dogs. The plasma adrenocorticotropic hormone (ACTH, and serum cortisol and cortisone concentrations were significantly lower at day 7 and 15 following corticotropin releasing hormone stimulation. After completion of CBX administration, the HSD11B1 mRNA expression was higher, and HSD11B2 mRNA expression was significantly lower in the pituitaries. Moreover, proopiomelanocortin mRNA expression was lower, and the ratio of ACTH-positive cells in the anterior pituitary was also significantly lower after CBX treatment. In adrenal glands treated with CBX, HSD11B1 and HSD11B2 mRNA expression were both lower compared to normal canine adrenal glands. The results of this study suggested that CBX inhibits ACTH secretion from pituitary due to altered 11HSD expressions, and is potentially useful for the treatment of canine Cushing's disease.

  4. Endomorphins and activation of the hypothalamo-pituitary-adrenal axis.

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    Coventry, T L; Jessop, D S; Finn, D P; Crabb, M D; Kinoshita, H; Harbuz, M S

    2001-04-01

    Endomorphin (EM)-1 and EM-2 are opioid tetrapeptides recently located in the central nervous system and immune tissues with high selectivity and affinity for the mu-opioid receptor. Intracerebroventricular (i.c.v.) administration of morphine stimulates the hypothalamo-pituitary-adrenal (HPA) axis. The present study investigated the effect of centrally administered EM-1 and EM-2 on HPA axis activation. Rats received a single i.c.v. injection of either EM-1 (0.1, 1.0, 10 microg), EM-2 (10 microg), morphine (10 microg), or vehicle (0.9% saline). Blood samples for plasma corticosterone determinations were taken immediately prior to i.c.v. administration and at various time points up to 4 h post-injection. Trunk blood, brains and pituitaries were collected at 4 h. Intracerebroventricular morphine increased plasma corticosterone levels within 30 min, whereas EM-1 and EM-2 were without effect. In addition, pre-treatment of i.c.v. EM-1 did not block the rise in corticosterone after morphine. Corticotrophin-releasing factor (CRF) mRNA and arginine vasopressin (AVP) mRNA in the paraventricular nucleus (PVN) and POMC mRNA in the anterior pituitary were found to be unaffected by either morphine or endomorphins. Since release of other opioids are elevated in response to acute stress, we exposed rats to a range of stressors to determine whether plasma EM-1 and EM-2 can be stimulated by HPA axis activation. Plasma corticosterone, ACTH and beta-endorphin were elevated following acute restraint stress, but concentrations of plasma EM-1-immunoreactivity (ir) and EM-2-ir did not change significantly. Corticosterone, ACTH and beta-endorphin were further elevated in adjuvant-induced arthritis (AA) rats by a single injection of lipopolysaccharide (LPS), but not by restraint stress. In conclusion, neither EM-1 or EM-2 appear to influence the regulation of the HPA axis. These data suggest that endomorphins may be acting on a different subset of the mu-opioid receptor than morphine. The

  5. Adolescent Survivors of Hurricane Katrina: A Pilot Study of Hypothalamic-Pituitary-Adrenal Axis Functioning

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    Pfefferbaum, Betty; Tucker, Phebe; Nitiéma, Pascal

    2015-01-01

    Background: The hypothalamic-pituitary-adrenal (HPA) axis constitutes an important biological component of the stress response commonly studied through the measurement of cortisol. Limited research has examined HPA axis dysregulation in youth exposed to disasters. Objective: This study examined HPA axis activation in adolescent Hurricane Katrina…

  6. Hypothalamic-pituitary-adrenal axis activity in older persons with and without a depressive disorder

    NARCIS (Netherlands)

    Rhebergen, D.; Korten, N. C. M.; Penninx, B. W. J. H.; Stek, M. L.; van der Mast, R. C.; Voshaar, R. Oude; Comijs, H. C.

    2015-01-01

    Background: Altered functioning of the hypothalamic-pituitary-adrenal axis (HPA-axis) has been associated with depression, but findings have been inconsistent. Among older depressed persons, both hyperactivity and hypo-activity of the HPA-axis were demonstrated. However, most studies were population

  7. Pituitary-Adrenal Axis in Prader Willi Syndrome

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    Olivia S. Edgar

    2016-01-01

    Full Text Available Purpose: Prader Willi syndrome (PWS is a rare genetic condition that has concurrent endocrinological insufficiencies. The presence of growth hormone deficiency has been well documented, but adrenal insufficiency (AI is not widely reported. A review was conducted to investigate its prevalence and relevance in PWS in both adults and children. Methodology: A literature review was performed with the search terms “Prader-Willi syndrome” and “adrenal insufficiency”. Results: The review found studies disagree on the prevalence and method of investigation of AI in PWS. Case studies demonstrate that patients with PWS are at risk of premature death, often secondary to respiratory infections. The possibility that this may be the result of the inability to mount an effective cortisol response has been studied, with some evidence confirming AI in PWS patients. Most reports agreed AI is present in PWS, however, Farholt et al. showed no HPA axis dysfunction in adults, suggesting that perhaps it is rare in adults, and children should be the focus of further studies. Conclusion: AI is present in some patients with PWS. Further research is required to ensure optimal treatment can be implemented and to prevent premature deaths related to adrenal insufficiency. Clinicians should have a low threshold for testing the adrenal axis and considering treatment for adrenal insufficiency in PWS patients.

  8. Relationship between the hypothalamic-pituitary-adrenal-axis and fatty acid metabolism in recurrent depression

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    Mocking, Roel J T; Ruhe, Eric; Assies, Johanna; Lok, Anja; Koeter, Maarten W J; Visser, Ieke; Bockting, Claudi L H; Schene, Aart H

    2013-01-01

    Alterations in hypothalamic-pituitary-adrenal (HPA)-axis activity and fatty acid (FA)-metabolism have been observed in (recurrent) major depressive disorder (MDD). Through the pathophysiological roles of FAs in the brain and cardiovascular system, a hypothesized relationship between HPA-axis activit

  9. Characterization of the hypothalamic-pituitary-adrenal-axis in familial longevity under resting conditions

    NARCIS (Netherlands)

    Jansen, S.W.; Roelfsema, F.; Akintola, A.A.; Oei, N.Y.; Cobbaert, C.M.; Ballieux, B.E.; van der Grond, J.; Westendorp, R.G.; Pijl, H.; van Heemst, D.

    2015-01-01

    Objective: The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched for lon

  10. Hypothalamic Pituitary Adrenal Axis Functioning in Reactive and Proactive Aggression in Children

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    Lopez-Duran, Nestor L.; Olson, Sheryl L.; Hajal, Nastassia J.; Felt, Barbara T.; Vazquez, Delia M.

    2009-01-01

    The purpose of this study was to examine the association between hypothalamic-pituitary-adrenal axis (HPA-axis) reactivity and proactive and reactive aggression in pre-pubertal children. After a 30-min controlled base line period, 73 7-year-old children (40 males and 33 females) were randomly assigned to one of two experimental tasks designed to…

  11. Association analyses of depression and genes in the hypothalamus-pituitary-adrenal axis

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    Buttenschøn, Henrietta Nørmølle; Krogh, Jesper; Nielsen, Marit Nyholm;

    2016-01-01

    OBJECTIVE: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme...

  12. Fetal hypothalamus-pituitary-adrenal axis on the road to parturition.

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    Schwartz, J; McMillen, I C

    2001-01-01

    1. Activity of the fetal hypothalamus-pituitary-adrenal (HPA) axis waxes and wanes as a function of gestational age. 2. In a number of species, including sheep, at the end of gestation there is an increase in HPA activity, as characterized by an increase in fetal plasma glucocorticoids. 3. To a certain degree, the hypothalamus, pituitary and adrenal all act autonomously and, therefore, may be thought of as contributing to the initiation of the signal that results in the increase in steroidogenesis before birth. 4. Because it integrates sensory information from beyond as well as within the HPA axis and likely triggers developmental changes within the pituitary, the hypothalamus may be a 'first among equals' in being the ultimate source of triggering information for the HPA axis.

  13. Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice

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    McNeilly, Alison D; Macfarlane, David P; O'Flaherty, Emmett

    2010-01-01

    Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5beta-reductase....

  14. Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

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    Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

    2006-01-01

    Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12 ye

  15. Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress

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    Jereme G. Spiers

    2015-01-01

    Full Text Available Glucocorticoids released from the adrenal gland in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA axis induce activity in the cellular reduction-oxidation (redox system. The redox system is a ubiquitous chemical mechanism allowing the transfer of electrons between donor/acceptors and target molecules during oxidative phosphorylation while simultaneously maintaining the overall cellular environment in a reduced state. The objective of this review is to present an overview of the current literature discussing the link between HPA axis-derived glucocorticoids and increased oxidative stress, particularly focussing on the redox changes observed in the hippocampus following glucocorticoid exposure.

  16. Anatomy of melancholia: focus on hypothalamic-pituitary-adrenal axis overactivity and the role of vasopressin.

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    Dinan, Timothy G

    2012-02-03

    Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA\\/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down-regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.

  17. [Correlations between the hypothalamo-pituitary-adrenal axis and the metabolic syndrome].

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    Góth, Miklós; Hubina, Erika; Korbonits, Márta

    2005-01-09

    The metabolic syndrome has several similarities with Cushing's syndrome (impaired glucose tolerance, hypertension, dyslipidemia, central obesity) suggesting that abnormalities in the regulation of the hypothalamic-pituitary-adrenal axis may have a link with the metabolic syndrome. Several studies suggested an association between the clinical signs of the metabolic syndrome and the increased hypothalamic-pituitary-adrenal axis activity based on increased cortisol concentration at 09.00 a.m. and increased cortisol response to corticotropin. According to the Barker hypothesis the fetal malnutrition could determine adult cardiovascular diseases (coronary heart disease, hypertension), some endocrine and metabolic disorders (obesity, type 2 diabetes and hyperlipidemia). The suggested mechanism of the phenomenon is that the suboptimal fetal nutrition results in glucocorticoid overproduction. The 11beta-hydroxysteroid dehydrogenase (converts biological inactive cortisone to cortisol and vice versa) is an important enzyme in cortisol metabolism. The increased expression of 11beta-hydroxysteroid dehydrogenase type 1 in fat tissue could lead to central obesity and impaired glucose tolerance. The hypothesis that increased corticotropin-releasing hormone production drives the overactive hypothalamo-pituitary-adrenal axis was not proven. Further investigations are needed to identify additional pathogenetic factors and to find new therapeutic possibilities.

  18. [A test for evaluation of pituitary-adrenal axis disregulation].

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    Rybnikova, E A; Mironova, V I; Pivina, S G

    2010-01-01

    In rat models, a modification of the fast feedback paradigm for the pituitary adrenocortical system applied to detect posttraumatic stress disorder (PTSD) was developed. Both standard and modified methods were used. In contrast to the standard method (injection of exogenous cortisol), the new modification suggested measuring blood corticosterone, rather than adrenocorticotropic hormone, at the early stages of development of the stress reaction (3, 10, 30, and 60 min of the exposure to stress factors). With the suggested modification, the fast feedback phenomenon was studied in reliable rat models of PTSD (stress-restress) and depression (learned helplessness). Fast pathological inhibition of the pituitary adrenocortical system by the fast feedback mechanism was revealed only during the simulated PTSD but not in the depressive-like state, which supported the specificity and validity of the developed modification of the test. Thus, the proposed methodological modification is a valid tool for diagnostics of the PTSD-specific fast feedback inhibition of the pituitary adrenocortical system in the animal models of this psychopathology.

  19. Neuromedins U and S involvement in the regulation of the hypothalamo - pituitary - adrenal axis.

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    Ludwik K. Malendowicz

    2012-12-01

    Full Text Available Abstract: We reviewed neuromedin U (NMU and neuromedin S (NMS involvement in the regulation of the hypothalamo - pituitary - adrenal (HPA axis function. NMU and NMS are structurally related and highly conserved neuropeptides. They exert biological effects via two GPCR receptors designated as NMUR1 and NMUR2 which show differential expression. NMUR1 is expressed predominantly at the periphery, while NMUR2 in the central nervous system. Elements of the NMU/NMS and their receptors network are also expressed in the HPA axis and progress in molecular biology techniques provided new information on their actions within this system. Several lines of evidence suggest that within the HPA axis NMU and NMS act at both hypothalamic and adrenal levels. Moreover, new data suggest that NMU and NMS are involved in central and peripheral control of the stress response.

  20. Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability

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    Vernon Suzanne D

    2007-02-01

    Full Text Available Abstract Background The body's primary stress management system is the hypothalamic pituitary adrenal (HPA axis. The HPA axis responds to physical and mental challenge to maintain homeostasis in part by controlling the body's cortisol level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases. Results We developed a structured model of the HPA axis that includes the glucocorticoid receptor (GR. This model incorporates nonlinear kinetics of pituitary GR synthesis. The nonlinear effect arises from the fact that GR homodimerizes after cortisol activation and induces its own synthesis in the pituitary. This homodimerization makes possible two stable steady states (low and high and one unstable state of cortisol production resulting in bistability of the HPA axis. In this model, low GR concentration represents the normal steady state, and high GR concentration represents a dysregulated steady state. A short stress in the normal steady state produces a small perturbation in the GR concentration that quickly returns to normal levels. Long, repeated stress produces persistent and high GR concentration that does not return to baseline forcing the HPA axis to an alternate steady state. One consequence of increased steady state GR is reduced steady state cortisol, which has been observed in some stress related disorders such as Chronic Fatigue Syndrome (CFS. Conclusion Inclusion of pituitary GR expression resulted in a biologically plausible model of HPA axis bistability and hypocortisolism. High GR concentration enhanced cortisol negative feedback on the hypothalamus and forced the HPA axis into an alternative, low cortisol state. This model can be used to explore mechanisms underlying disorders of the HPA axis.

  1. Effect of intracerebroventricular injection of histamine on blood sugar level and hypothalamo-pituitary adrenal axis of rats.

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    Trivedi, C P; Modi, N T; Balothia, R K

    1976-01-01

    Intraventricular injection of histamine and normal saline in rats caused a marked fall in adrenal ascorbic acid indicating a stimulatory effect of both on pituitary adrenal axis. Intraventricularly injected histamine caused significant hypoglycaemia also in rats as compared to control series.

  2. The Minimal Model of the Hypothalamic-Pituitary-Adrenal Axis

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    Vinther, Frank; Andersen, Morten; Ottesen, Johnny T.

    2011-01-01

    thereof. The second part of the paper concerns a specific realization of the minimal model in which feedback functions are built explicitly using receptor dynamics. Using physiologically reasonable parameter values, along with the results of the general case, it is demonstrated that un...... that influence the dynamics of the HPA axis, i.e. a negative feedback from cortisol on CRH and ACTH. Therefore we term our model the minimal model. The minimal model, encompasses a wide class of different realizations, obeying only a few physiologically reasonable demands. The results include the existence...... emerge from the model. Sufficient criteria for local stability of the fixed point, and an easily applicable sufficient criteria guaranteeing global stability of the fixed point, is formulated. If the latter is fulfilled, ultradian rhythm is an impossible outcome of the minimal model and all realizations...

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

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    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.

  4. Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA axis

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    Mello Andrea de Abreu Feijó de

    2003-01-01

    Full Text Available Over the past 50 years, relationships between stress and the neurobiological changes seen in psychiatric disorders have been well-documented. A major focus of investigations in this area has been the role of the hypothalamic-pituitary-adrenal (HPA axis, both as a marker of stress response and as a mediator of additional downstream pathophysiologic changes. This review examines the emerging literature concerning the relationship between stress, HPA axis function, and depression, as well as the role of early life stress as an important risk factor for HPA axis dysregulation. The more recent studies reviewed suggest that the prominence of HPA axis hyperactivity in adults with depressive and anxiety disorders may constitute a link between the occurrence of adversity in childhood and the development of adult psychopathology

  5. Prenatal xenobiotic exposure and intrauterine hypothalamus-pituitary-adrenal axis programming alteration.

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    Zhang, Chong; Xu, Dan; Luo, Hanwen; Lu, Juan; Liu, Lian; Ping, Jie; Wang, Hui

    2014-11-05

    The hypothalamic-pituitary-adrenal (HPA) axis is one of the most important neuroendocrine axes and plays an important role in stress defense responses before and after birth. Prenatal exposure to xenobiotics, including environmental toxins (such as smoke, sulfur dioxide and carbon monoxide), drugs (such as synthetic glucocorticoids), and foods and beverage categories (such as ethanol and caffeine), affects fetal development indirectly by changing the maternal status or damaging the placenta. Certain xenobiotics (such as caffeine, ethanol and dexamethasone) may also affect the fetus directly by crossing the placenta into the fetus due to their lipophilic properties and lower molecular weights. All of these factors probably result in intrauterine programming alteration of the HPA axis, which showed a low basal activity but hypersensitivity to chronic stress. These alterations will, therefore, increase the susceptibility to adult neuropsychiatric (such as depression and schizophrenia) and metabolic diseases (such as hypertension, diabetes and non-alcoholic fatty liver disease). The "over-exposure of fetuses to maternal glucocorticoids" may be the main initiation factor by which the fetal HPA axis programming is altered. Meantime, xenobiotics can directly induce abnormal epigenetic modifications and expression on the important fetal genes (such as hippocampal glucocorticoid receptor, adrenal steroidogenic acute regulatory protein, et al) or damage by in situ oxidative metabolism of fetal adrenals, which may also be contributed to the programming alteration of fetal HPA axis.

  6. Modelling cholesterol effects on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis.

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    Marković, Vladimir M; Čupić, Željko; Maćešić, Stevan; Stanojević, Ana; Vukojević, Vladana; Kolar-Anić, Ljiljana

    2016-03-01

    A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis with cholesterol as a dynamical variable was derived to investigate the effects of cholesterol, the primary precursor of all steroid hormones, on the ultradian and circadian HPA axis activity. To develop the model, the parameter space was systematically examined by stoichiometric network analysis to identify conditions for ultradian oscillations, determine conditions under which dynamic transitions, i.e. bifurcations occur and identify bifurcation types. The bifurcations were further characterized using numerical simulations. Model predictions agree well with empirical findings reported in the literature, indicating that cholesterol levels may critically affect the global dynamics of the HPA axis. The proposed model provides a base for better understanding of experimental observations, it may be used as a tool for designing experiments and offers useful insights into the characteristics of basic dynamic regulatory mechanisms that, when impaired, may lead to the development of some modern-lifestyle-associated diseases.

  7. Improvement of kidney yang syndrome by icariin through regulating hypothalamus-pituitary-adrenal axis.

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    An, Rui; Li, Bo; You, Li-sha; Wang, Xin-hong

    2015-10-01

    To investigate whether Epimedium brevicornu Maxim (EB) and icariin could exert their protective effects on hydrocortisone induced (HCI) rats by regulating the hypothalamus-pituitary-adrenal (HPA) axis and endocrine system and the possible mechanism. Male 10-week-old Sprague Dawley (SD) rats were allotted to 6 groups (A-F) with 12 each, group A was injected normal saline (NS) 3 mL/kg day intraperitoneally, group A and B were given NS 6 mL/kg day by gastrogavage, group B-F were injected hydrocortisone 15 mg/kg intraperitoneally, group C and D were given EB 8 or 5 g/(kg day) by gastrogavage, group E and F were given icariin 25 or 50 mg/(kg day) by gastrogavage. Gene expressions of hypothalamus corticotropin releasing hormone (CRH) and pituitary proopiomelanocortin (POMC) were detected by reverse transcription-polymerase chain reaction (RT-PCR), and protein of pituitary POMC by Western-blot. The serum T4, testosterone, cortisol and POMC mRNA expression were increased after treatment with EB or icariin in HCI rats, the serum CRH and the hypothalamus CRH mRNA expression released from hypothalamus corticotropin decreased compared with group B (P<0.05).The treatment with only icariin increased serum adrenocorticotropic hormone (ACTH) compared with group B (P<0.05). EB and icariin might be therapeutically beneficial in the treatment of HCI rats through attuning the HPA axis and endocrine system which was involved in the release of CRH in hypothalamic, and the production of POMC-derived peptide ACTH in anterior pituitary, the secretion of corticosteroids in adrenal cortex.

  8. Stability analysis of a hypothalamic-pituitary-adrenal axis model with inclusion of glucocorticoid receptor and memory

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    Kaslik, Eva; Navolan, Dan Bogdan; Neamţu, Mihaela

    2017-01-01

    This paper analyzes a four-dimensional model of the hypothalamic-pituitary-adrenal (HPA) axis that includes the influence of the glucocorticoid receptor in the pituitary. Due to the spatial separation between the hypothalamus, pituitary and adrenal glands, distributed time delays are introduced in the mathematical model. The existence of the positive equilibrium point is proved and a local stability and bifurcation analysis is provided, considering several types of delay kernels. The fractional-order model with discrete time delays is also taken into account. Numerical simulations are provided to illustrate the effectiveness of the theoretical findings.

  9. Hypothalamic Norepinephrine Mediates Acupunctural Effects on Hypothalamic-Pituitary-Adrenal Axis During Ethanol Withdrawal.

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    Zhao, Zheng Lin; Kim, Sang Chan; Zhang, Jie; Liu, Hong Feng; Lee, Bong Hyo; Jang, Eun Young; Lee, Chul Won; Cho, Il Je; An, Won G; Yang, Chae Ha; Kim, Young Woo; Zhao, Rong Jie; Wu, Yi Yan

    2016-02-01

    A previous study demonstrated that acupuncture at ST36 (Zu-San-Li) attenuates ethanol withdrawal (EW)-induced hyperactivation of the hypothalamic-pituitary-adrenal axis in rats. The current study investigated the involvement of hypothalamic norepinephrine (NE) in that process. Rats were intraperitoneally treated with 3 g/kg/d of ethanol or saline for 28 days. After 24 hours of EW, acupuncture was applied to rats at bilateral ST36 points or at nonacupoints (tail) for 1 minute. A high-performance liquid chromatography analysis showed that EW significantly increased both the NE and the 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels in the hypothalamic paraventricular nucleus (PVN). Western blot analysis also revealed that EW markedly elevated the phosphorylation rates of tyrosine hydroxylase (TH), but spared TH protein expression in the PVN. However, acupuncture at ST36, but not at nonacupoints, greatly inhibited the increase in the hypothalamic NE, MHPG, and phosphorylation rates of TH. Additionally, postacupuncture infusion of NE into the PVN significantly attenuated the inhibitory effects of acupuncture at ST36 on the oversecretion of plasma corticosterone during EW. These results suggest that acupuncture at ST36 inhibits EW-induced hyperactivation of the hypothalamic NEergic system to produce therapeutic effects on the hypothalamic-pituitary-adrenal axis.

  10. Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis

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    Čupić, Željko; Marković, Vladimir M.; Maćešić, Stevan; Stanojević, Ana; Damjanović, Svetozar; Vukojević, Vladana; Kolar-Anić, Ljiljana

    2016-03-01

    Dynamic properties of a nonlinear five-dimensional stoichiometric model of the hypothalamic-pituitary-adrenal (HPA) axis were systematically investigated. Conditions under which qualitative transitions between dynamic states occur are determined by independently varying the rate constants of all reactions that constitute the model. Bifurcation types were further characterized using continuation algorithms and scale factor methods. Regions of bistability and transitions through supercritical Andronov-Hopf and saddle loop bifurcations were identified. Dynamic state analysis predicts that the HPA axis operates under basal (healthy) physiological conditions close to an Andronov-Hopf bifurcation. Dynamic properties of the stress-control axis have not been characterized experimentally, but modelling suggests that the proximity to a supercritical Andronov-Hopf bifurcation can give the HPA axis both, flexibility to respond to external stimuli and adjust to new conditions and stability, i.e., the capacity to return to the original dynamic state afterwards, which is essential for maintaining homeostasis. The analysis presented here reflects the properties of a low-dimensional model that succinctly describes neurochemical transformations underlying the HPA axis. However, the model accounts correctly for a number of experimentally observed properties of the stress-response axis. We therefore regard that the presented analysis is meaningful, showing how in silico investigations can be used to guide the experimentalists in understanding how the HPA axis activity changes under chronic disease and/or specific pharmacological manipulations.

  11. Food and the circadian activity of the hypothalamic-pituitary-adrenal axis

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    A.M.O. Leal

    1997-12-01

    Full Text Available Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or" zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states

  12. Hypothalamic-Pituitary-Adrenal Axis Programming after Recurrent Hypoglycemia during Development

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    Raghavendra Rao

    2015-08-01

    Full Text Available Permanent brain injury is a complication of recurrent hypoglycemia during development. Recurrent hypoglycemia also has adverse consequences on the neuroendocrine system. Hypoglycemia-associated autonomic failure, characterized by ineffective glucose counterregulation during hypoglycemia, is well described in children and adults on insulin therapy for diabetes mellitus. Whether recurrent hypoglycemia also has a programming effect on the hypothalamus-pituitary-adrenal cortex (HPA axis has not been well studied. Hypoglycemia is a potent stress that leads to increased glucocorticoid secretion in all age groups, including the perinatal period. Other conditions associated with exposure to excess glucocorticoid in the perinatal period have a programming effect on the HPA axis activity. Limited animal data suggest the possibility of similar programming effect after recurrent hypoglycemia in the postnatal period. The age at exposure to hypoglycemia likely determines the HPA axis response in adulthood. Recurrent hypoglycemia in the early postnatal period likely leads to a hyperresponsive HPA axis, whereas recurrent hypoglycemia in the late postnatal period lead to a hyporesponsive HPA axis in adulthood. The age-specific programming effects may determine the neuroendocrine response during hypoglycemia and other stressful events in individuals with history of recurrent hypoglycemia during development.

  13. The critical importance of the fetal hypothalamus-pituitary-adrenal axis [version 1; referees: 3 approved

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    Charles E. Wood

    2016-01-01

    Full Text Available The fetal hypothalamus-pituitary-adrenal (HPA axis is at the center of mechanisms controlling fetal readiness for birth, survival after birth and, in several species, determination of the timing of birth. Stereotypical increases in fetal HPA axis activity at the end of gestation are critical for preparing the fetus for successful transition to postnatal life. The fundamental importance in fetal development of the endogenous activation of this endocrine axis at the end of gestation has led to the use of glucocorticoids for reducing neonatal morbidity in premature infants. However, the choice of dose and repetition of treatments has been controversial, raising the possibility that excess glucocorticoid might program an increased incidence of adult disease (e.g., coronary artery disease and diabetes. We make the argument that because of the critical importance of the fetal HPA axis and its interaction with the maternal HPA axis, dysregulation of cortisol plasma concentrations or inappropriate manipulation pharmacologically can have negative consequences at the beginning of extrauterine life and for decades thereafter.

  14. Predicting mental disorders from hypothalamic-pituitary-adrenal axis functioning : a 3-year follow-up in the TRAILS study

    NARCIS (Netherlands)

    Nederhof, E.; van Oort, F. V. A.; Bouma, E. M. C.; Laceulle, O. M.; Oldehinkel, A. J.; Ormel, J.

    2015-01-01

    Background. Hypothalamic-pituitary-adrenal axis functioning, with cortisol as its major output hormone, has been presumed to play a key role in the development of psychopathology. Predicting affective disorders from diurnal cortisol levels has been inconclusive, whereas the predictive value of stres

  15. Meta-analysis and meta-regression of hypothalamic-pituitary-adrenal axis activity in functional somatic disorders

    NARCIS (Netherlands)

    Tak, Lineke M; Cleare, Anthony J; Ormel, Johan; Manoharan, Andiappan; Kok, Iris C; Wessely, Simon; Rosmalen, Judith G M

    2011-01-01

    Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is the most investigated biological risk marker in functional somatic disorders (FSDs), such as chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS). Our aim was to assess whether there is an association be

  16. Differential flatness properties and adaptive control of the hypothalamic-pituitary-adrenal axis model

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    Rigatos, Gerasimos

    2016-12-01

    It is shown that the model of the hypothalamic-pituitary-adrenal gland axis is a differentially flat one and this permits to transform it to the so-called linear canonical form. For the new description of the system's dynamics the transformed control inputs contain unknown terms which depend on the system's parameters. To identify these terms an adaptive fuzzy approximator is used in the control loop. Thus an adaptive fuzzy control scheme is implemented in which the unknown or unmodeled system dynamics is approximated by neurofuzzy networks and next this information is used by a feedback controller that makes the state variables (CRH - corticotropin releasing hormone, adenocortocotropic hormone - ACTH, cortisol) of the hypothalamic-pituitary-adrenal gland axis model converge to the desirable levels (setpoints). This adaptive control scheme is exclusively implemented with the use of output feedback, while the state vector elements which are not directly measured are estimated with the use of a state observer that operates in the control loop. The learning rate of the adaptive fuzzy system is suitably computed from Lyapunov analysis, so as to assure that both the learning procedure for the unknown system's parameters, the dynamics of the observer and the dynamics of the control loop will remain stable. The performed Lyapunov stability analysis depends on two Riccati equations, one associated with the feedback controller and one associated with the state observer. Finally, it is proven that for the control scheme that comprises the feedback controller, the state observer and the neurofuzzy approximator, an H-infinity tracking performance can be succeeded.

  17. Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity

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    Marcella Balbo

    2010-01-01

    Full Text Available The daily rhythm of cortisol secretion is relatively stable and primarily under the influence of the circadian clock. Nevertheless, several other factors affect hypothalamo-pituitary-adrenal (HPA axis activity. Sleep has modest but clearly detectable modulatory effects on HPA axis activity. Sleep onset exerts an inhibitory effect on cortisol secretion while awakenings and sleep offset are accompanied by cortisol stimulation. During waking, an association between cortisol secretory bursts and indices of central arousal has also been detected. Abrupt shifts of the sleep period induce a profound disruption in the daily cortisol rhythm, while sleep deprivation and/or reduced sleep quality seem to result in a modest but functionally important activation of the axis. HPA hyperactivity is clearly associated with metabolic, cognitive and psychiatric disorders and could be involved in the well-documented associations between sleep disturbances and the risk of obesity, diabetes and cognitive dysfunction. Several clinical syndromes, such as insomnia, depression, Cushing's syndrome, sleep disordered breathing (SDB display HPA hyperactivity, disturbed sleep, psychiatric and metabolic impairments. Further research to delineate the functional links between sleep and HPA axis activity is needed to fully understand the pathophysiology of these syndromes and to develop adequate strategies of prevention and treatment.

  18. Interaction of PGHS-2 and glutamatergic mechanisms controlling the ovine fetal hypothalamus-pituitary-adrenal axis.

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    Knutson, Nathan; Wood, Charles E

    2010-07-01

    Prostaglandins, generated within the fetal brain, are integral components of the mechanism controlling the fetal hypothalamus-pituitary-adrenal (HPA) axis. Previous studies in this laboratory demonstrated that prostaglandin G/H synthase isozyme 2 (PGHS-2) inhibition reduces the fetal HPA axis response to cerebral hypoperfusion, blocks the preparturient rise in fetal plasma ACTH concentration, and delays parturition. We also discovered that blockade of N-methyl-d-aspartate (NMDA) receptors reduces the fetal ACTH response to cerebral hypoperfusion. The present study was designed to test the hypothesis that PGHS-2 action and the downstream effect of HPA axis stimulation are stimulated by NMDA-mediated glutamatergic neurotransmission. Chronically catheterized late-gestation fetal sheep (n = 8) were injected with NMDA (1 mg iv). All responded with increases in fetal plasma ACTH and cortisol concentrations. Pretreatment with resveratrol (100 mg iv, n = 5), a specific inhibitor of PGHS-1, did not alter the magnitude of the HPA axis response to NMDA. Pretreatment with nimesulide (10 mg iv, n = 6), a specific inhibitor of PGHS-2, significantly reduced the HPA axis response to NMDA. To further explore this interaction, we injected NMDA in six chronically catheterized fetal sheep that were chronically infused with nimesulide (n = 6) at a rate of 1 mg/day into the lateral cerebral ventricle for 5-7 days. In this group, there was no significant ACTH response to NMDA. Finally, we tested whether the HPA axis response to prostaglandin E(2) (PGE(2)) is mediated by NMDA receptors. Seven chronically catheterized late-gestation fetal sheep were injected with 100 ng of PGE(2), which significantly increased fetal plasma ACTH and cortisol concentrations. Pretreatment with ketamine (10 mg iv), an NMDA antagonist, did not alter the ACTH or cortisol response to PGE(2). We conclude that generation of prostanoids via the action of PGHS-2 in the fetal brain augments the fetal HPA axis response

  19. Hypothalamic-pituitary-adrenal axis responses of horses to therapeutic riding program: effects of different riders.

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    Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Ferlazzo, Adriana

    2013-06-13

    In order to determine whether therapeutic riding could result in higher levels of stress than recreational riding, hypothalamic-pituitary-adrenal (HPA) axis response was evaluated in six horses by monitoring circulating β-endorphin, ACTH and cortisol concentrations. Horses were already accustomed to be trained both for therapy and riding school activity since 2004. Intervention consisted of 60-minute therapeutic sessions, two times per week for 6weeks with different riders: disabled and recreational riders (session A and B respectively). The therapeutic riders' group (A) consisted of six children with psychomotor disabilities; the recreational riders' group (B) consisted of six healthy children without any previous horse riding experience. Horses were asked to perform the same gaits and exercises at all sessions, both with disabled and healthy users. The statistical analysis showed that during both sessions the mean basal β-endorphin and ACTH levels of horses did not show any significant changes, while the one way RM-ANOVA showed significant effects of sessions A on the cortisol (F=11.50; PHorses submitted to sessions A showed lower cortisol levels both at 5min (Phorses and for the variables settled, HPA axis was less responsive to disabled than healthy, recreational riders. Among the endocrine responses, cortisol was one of the indicators of HPA axis stress response.

  20. The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats.

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    Merlo, Eduardo; Podratz, Priscila L; Sena, Gabriela C; de Araújo, Julia F P; Lima, Leandro C F; Alves, Izabela S S; Gama-de-Souza, Letícia N; Pelição, Renan; Rodrigues, Lívia C M; Brandão, Poliane A A; Carneiro, Maria T W D; Pires, Rita G W; Martins-Silva, Cristina; Alarcon, Tamara A; Miranda-Alves, Leandro; Silva, Ian V; Graceli, Jones B

    2016-08-01

    Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus-pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-γ protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function.

  1. Hypothalamo-pituitary-adrenal axis, glucose metabolism and TNF-α in narcolepsy.

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    Maurovich-Horvat, Eszter; Keckeis, Marietta; Lattová, Zuzana; Kemlink, David; Wetter, Thomas-Christian; Schuld, Andreas; Sonka, Karel; Pollmächer, Thomas

    2014-08-01

    Narcolepsy with cataplexy is caused by a deficiency in the production of hypocretin/orexin, which regulates sleep and wakefulness, and also influences appetite, neuroendocrine functions and metabolism. In this case-control study, 11 patients with narcolepsy with cataplexy and 11 healthy adults underwent an oral glucose tolerance test, and dexamethasone suppression/corticotropin-releasing hormone stimulation test. The average age of patients and controls was 35.1 ± 13.2 and 41.0 ± 2.9 years, respectively, body mass index was 28.1 ± 6.6 and 25.5 ± 4.7 kg m(-2) . We did not find evidence of a significantly increased prevalence of disturbed glucose tolerance in patients with narcolepsy. After hypothalamo-pituitary-adrenal axis suppression, the number of non-suppressors did not differ between the groups, indicating normal negative feedback sensitivity. The level of cortisol after dexamethasone suppression was significantly lower in patients with narcolepsy, suggesting a slight basal downregulation and/or a slightly increased negative feedback sensitivity of the major endocrine stress system in narcolepsy. Following corticotropin-releasing hormone stimulation, there were no significant differences in levels of adrenocorticotropic hormone or cortisol, and in adrenocortical responsivity to adrenocorticotropic hormone. Finally, patients with narcolepsy displayed significantly higher plasma levels of tumour necrosis factor alpha, soluble tumour necrosis factor receptor p55, soluble tumour necrosis factor receptor p75 and interleukin 6 after adjustment for body mass index. The present study confirms that narcolepsy by itself is not associated with disturbances of glucose metabolism, but goes along with a subtle dysregulation of inflammatory cytokine production. We also found that dynamic hypothalamo-pituitary-adrenal system response is not altered, whereas negative feedback to dexamethasone might be slightly enhanced.

  2. Depression, hypothalamic pituitary adrenal axis, and hippocampal and entorhinal cortex volumes--the SMART Medea study.

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    Gerritsen, Lotte; Comijs, Hannie C; van der Graaf, Yolanda; Knoops, Arnoud J G; Penninx, Brenda W J H; Geerlings, Mirjam I

    2011-08-15

    Structural brain changes have often been found in major depressive disorder (MDD), and it is thought that hypothalamic-pituitary-adrenal (HPA) axis hyperactivity may explain this relation. We investigated the association of MDD and history of depression with hippocampal and entorhinal cortex volumes and whether HPA axis activity explained this association. In 636 participants with a history of atherosclerotic disease (mean age 62 ± 9 years, 81% male) from the second Manifestation of ARTerial disease-Memory depression and aging (SMART-Medea) study, a 12-month diagnosis of MDD and history of depression were assessed. Age of first depressive episode was classified into early-onset depression (< 50 years) and late-onset depression (≥ 50 years). HPA axis regulation was assessed by four morning saliva samples, two evening samples, and one awakening sample after .5 mg dexamethasone. Hippocampus and entorhinal cortex volume were manually outlined on three-dimensional T1-weighted magnetic resonance images. General linear models adjusted for demographics, vascular risk, antidepressant use, and white matter lesions showed that ever having had MDD was associated with smaller hippocampal volumes but not with entorhinal cortex volumes. Remitted MDD was related to smaller entorhinal cortex volumes (p < .05). Participants with early-onset depression had smaller hippocampal volumes than those who were never depressed (p < .05), whereas participants with late-onset depression had smaller entorhinal cortex volumes (p < .05). HPA axis activity did not explain these differences. We found differential associations of age of onset of depression on hippocampal and entorhinal cortex volumes, which could not be explained by alterations in HPA axis regulation. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome.

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    Kim, Hee Kyung; Yoon, Jee Hee; Jeong, Yun Ah; Kang, Ho Cheol

    2016-12-01

    In subclinical Cushing syndrome (SC), it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA) axis after adrenalectomy between patients with overt Cushing syndrome (OC) and SC remain unknown. Thirty-six patients (10 with OC and 26 with SC) with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH) stimulation test. Levels of basal 24-hour urine free cortisol (UFC), serum cortisol after an overnight dexamethasone suppression test (DST), and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001), with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001). The HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.

  4. The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome

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    Hee Kyung Kim

    2016-12-01

    Full Text Available BackgroundIn subclinical Cushing syndrome (SC, it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA axis after adrenalectomy between patients with overt Cushing syndrome (OC and SC remain unknown.MethodsThirty-six patients (10 with OC and 26 with SC with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH stimulation test.ResultsLevels of basal 24-hour urine free cortisol (UFC, serum cortisol after an overnight dexamethasone suppression test (DST, and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001, with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001.ConclusionThe HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.

  5. Hypothalamic-pituitary-adrenal axis activity in patients with pathological gambling and internet use disorder.

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    Geisel, Olga; Panneck, Patricia; Hellweg, Rainer; Wiedemann, Klaus; Müller, Christian A

    2015-03-30

    Alterations in secretion of stress hormones within the hypothalamic-pituitary-adrenal (HPA) axis have repeatedly been found in substance-related addictive disorders. It has been suggested that glucocorticoids might contribute to the development and maintenance of substance use disorders by facilitatory effects on behavioral responses to substances of abuse. The objective of this pilot study was to investigate HPA axis activity in patients with non-substance-related addictive disorders, i.e. pathological gambling and internet use disorder. We measured plasma levels of copeptin, a vasopressin surrogate marker, adrenocorticotropic hormone (ACTH) and cortisol in male patients with pathological gambling (n=14), internet use disorder (n=11) and matched healthy controls for pathological gambling (n=13) and internet use disorder (n=10). Plasma levels of copeptin, ACTH and cortisol in patients with pathological gambling or internet use disorder did not differ among groups. However, cortisol plasma levels correlated negatively with the severity of pathological gambling as measured by the PG-YBOCS. Together with our findings of increased serum levels of brain-derived neurotrophic factor (BDNF) in pathological gambling but not internet use disorder, these results suggest that the pathophysiology of pathological gambling shares some characteristics with substance-related addictive disorders on a neuroendocrinological level, whereas those similarities could not be observed in internet use disorder.

  6. Hypothalamic-pituitary-adrenal axis function in patients with complex regional pain syndrome type 1.

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    Park, Jai Y; Ahn, Ryun S

    2012-09-01

    An exaggerated inflammatory process is considered an important pathophysiological feature of complex regional pain syndrome type 1 (CRPS-1). The hypothalamic-pituitary-adrenal (HPA) axis serves as a negative feedback mechanism for inflammatory processes. The present study examined the HPA axis function in patients with CRPS-1 by a determination of cortisol concentrations in saliva. Three sets of saliva samples were sequentially collected from 24 patients with CRPS-1 during medication (on-Med), 72 h after stopping medication (off-Med) and 8h after the oral administration of 1mg dexamethasone. One set of saliva samples was collected from healthy controls. The cortisol awakening response (CAR) and diurnal cortisol decline (DCD) were used as indices for HPA axis function. Cortisol levels during the post-awakening period in patients were increased following withdrawal of medications. The CAR during the off-Med condition was disappeared after administration of dexamethasone. Among the examined CRPS-related numerical variables, the frequency of spontaneous pain attacks showed relationships with the indices of HPA axis function. After classifying the patients into two subgroups, we observed that the CAR and DCD in patient who had a relatively high frequency of spontaneous pain attacks (subgroup 5 ≤) were lower and less steep than those in patient who had a relatively low frequency of spontaneous pain attacks (subgroup 0-4) for the on- and off-Med conditions. The CAR and DCD in subgroup 5 ≤ during their off-Med condition were comparable to those in controls. These results suggest that the increase in frequency of spontaneous pain attacks is associated with a reduced CAR and flattened DCD in patients CRPS-1.

  7. Study of hypothalamic pituitary adrenal axis in patients of membranous nephropathy receiving modified Ponticelli regimen

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    R Ramachandran

    2015-01-01

    Full Text Available Pulse methyl prednisolone followed by oral prednisolone and abrupt switch to chlorambucil/cyclophosphamide (Ponticelli/modified Ponticelli regimen is used in patients with idiopathic membranous nephropathy. This therapy where steroids are stopped abruptly is unphysiologic and expected to have hypothalamic pituitary adrenal (HPA axis suppression; however, this has not been evaluated. A total of 13 consecutive adult patients with idiopathic membranous nephropathy who had completed modified Ponticelli regimen were studied. The regimen included administration of pulse methylprednisolone 1 g for 3 days followed by oral prednisolone 0.5 mg/kg/day for 27 days followed by oral cyclophosphamide at a dose of 2 mg/kg/day for the next month. This was repeated for three courses. Patients who had received corticosteroids prior to therapy were excluded. The HPA axis was evaluated after 1 month of completing the last course of steroid therapy. The evaluation was done using a low-dose adrenocorticotropic hormone stimulation test. A single intravenous bolus dose of synacthen (1 μg was given at 9.00 am and the serum cortisol levels were estimated by radioimmunoassay at 0, 30, and 60 min. A peak cortisol level of 550 nmol/L or higher was considered as normal. Mean baseline cortisol levels was 662.3 ± 294.6 nmol/L and peak cortisol level was 767 ± 304.4 nmol/L. A total of 6 patients (46.2% had low basal cortisol levels, only 3 (23% had both basal and peak cortisol levels < 550 nmol/L suggestive of HPA axis suppression. To conclude, 23% of patients had suppression of HPA axis after modified Ponticelli regimen.

  8. Activation of the hypothalamic-pituitary-adrenal axis in adults with mineralocorticoid receptor haploinsufficiency.

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    Walker, Brian R; Andrew, Ruth; Escoubet, Brigitte; Zennaro, Maria-Christina

    2014-08-01

    Mineralocorticoid receptors (MRs) contribute to the negative feedback of the hypothalamic-pituitary-adrenal (HPA) axis in rodents. Studies with MR antagonists suggest a similar role in humans. The objective of the study was to establish whether loss-of-function mutations in NR3C2, encoding MR, cause activation of the HPA axis. This was a case-control study in members of pedigrees from the PHA1.NET cohort, comprising patients with pseudohypoaldosteronism type 1 (PHA1) who are heterozygous for loss-of-function mutations in NR3C2 and healthy controls who are unaffected family members. Twelve adult patients with PHA1 (six men, six women) and 20 age-matched healthy controls (seven men, 13 women) participated in the study. Patients with PHA1 had higher morning plasma cortisol (816 ± 85 vs 586 ± 50 nmol/L, P = .02) and increased 24-hour urinary excretion of cortisol metabolites (985 ± 150 vs 640 ± 46 μg/mmol creatinine, P = .03), independently of gender. After adjustment for gender, age, PHA1 diagnosis, and percentage body fat, higher plasma cortisol was associated with higher plasma renin, lower serum high-density lipoprotein-cholesterol, and higher waist circumference but not with blood pressure, carotid intima-media thickness, or echocardiographic parameters. Haploinsufficiency of MR in PHA1 causes HPA axis activation, providing genetic evidence that MR contributes to negative feedback in the human HPA axis. With limited sample size, initial indications suggest the resulting hypercortisolemia is related to the severity of MR deficiency and has adverse effects mediated by glucocorticoid receptors on liver lipid metabolism and adipose tissue distribution but does not adversely affect cardiac and vascular remodeling in the absence of normal signaling through the MR.

  9. Hypothalamic-pituitary-adrenal axis response to stress in male DUI recidivists.

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    Couture, Sophie; Brown, Thomas G; Ouimet, Marie Claude; Gianoulakis, Christina; Tremblay, Jacques; Carbonneau, René

    2008-01-01

    Cortisol is a stress hormone mediated by the hypothalamic-pituitary-adrenal (HPA) axis and a psychobiological marker of genetic risk for alcoholism and other high-risk behavioural characteristics. In previous work with driving under the influence of alcohol (DUI) recidivists, we uncovered a significant inverse relationship between the frequency of past DUI convictions and salivary cortisol, whose strength surpassed those observed between DUI frequency and measures of alcohol abuse and other DUI-related characteristics. This finding emerged using a methodology not specifically contrived to test this relationship. The goals of this follow-up study were to (a) examine if a standardized stress-induction protocol would produce a significant inverse relationship between cortisol response and number of DUI offences; and (b) clarify whether HPA axis dysregulation could be linked to particular DUI-related behavioural correlates, such as alcohol use severity, sensation seeking, and antisocial features. Thirty male DUI recidivists were recruited as well as 11 male non-DUI drivers as a comparison group. Results indicated an inverse relationship between DUI frequency and cortisol response (r(39)=-0.36, p=0.021), as well as a lower cortisol response in DUI offenders than the comparison group (F(1,39)=5.71, p=0.022). Finally, for recidivists, hierarchical regression analyses indicated that experience seeking (R(2)=0.23, p=0.008), followed by number of cigarettes smoked daily ((Delta)R(2)=0.12, p=0.031), combined to explain 35% of the variance in cortisol (F(2,29)=7.26, p=0.003). These findings indicate that severe recidivism may have psychobiological underpinnings, and that HPA axis dysregulation appears to be a mechanism common to high-risk behaviours including DUI recidivism, sensation seeking, and cigarette smoking.

  10. Renin-Angiotensin-aldosterone system and hypothalamic-pituitary-adrenal axis in hospitalized newborn foals.

    Science.gov (United States)

    Dembek, K A; Onasch, K; Hurcombe, S D A; MacGillivray, K C; Slovis, N M; Barr, B S; Reed, S M; Toribio, R E

    2013-01-01

    The renin-angiotensin-aldosterone system (RAAS) and hypothalamic-pituitary-adrenal axis (HPAA) and their interactions during illness and hypoperfusion are important to maintain organ function. HPAA dysfunction and relative adrenal insufficiency (RAI) are common in septic foals. Information is lacking on the RAAS and mineralocorticoid response in the context of RAI in newborn sick foals. To investigate the RAAS, as well as HPAA factors that interact with the RAAS, in hospitalized foals, and to determine their association with clinical findings. We hypothesized that critical illness in newborn foals results in RAAS activation, and that inappropriately low aldosterone concentrations are part of the RAI syndrome of critically ill foals. A total of 167 foals ≤3 days of age: 133 hospitalized (74 septic, 59 sick nonseptic) and 34 healthy foals. Prospective, multicenter, cross-sectional study. Blood samples were collected on admission. Plasma renin activity (PRA) and angiotensin-II (ANG-II), aldosterone, ACTH, and cortisol concentrations were measured in all foals. ANG-II, aldosterone, ACTH, and cortisol concentrations as well as ACTH/aldosterone and ACTH/cortisol ratios were higher in septic foals compared with healthy foals (P < .05). No difference in PRA between groups was found. High serum potassium and low serum chloride concentrations were associated with hyperaldosteronemia in septic foals. RAAS activation in critically ill foals is characterized by increased ANG-II and aldosterone concentrations. Inappropriately low cortisol and aldosterone concentrations defined as high ACTH/cortisol and ACTH/aldosterone ratios in septic foals suggest that RAI is not restricted to the zona fasciculata in critically ill newborn foals. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  11. Acupoint specificity on acupuncture regulation of hypothalamic- pituitary-adrenal cortex axis function.

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    Wang, Shao-jun; Zhang, Jiao-jiao; Yang, Hao-yan; Wang, Fang; Li, Si-ting

    2015-03-27

    The hypothalamus is an essential part of the brain that responds to a variety of signaling including stressful stimulations and acupuncture signals. It is also the key element of the hypothalamic-pituitary-adrenal cortex axis(HPAA). The effect of acupuncture is transmitted into the brain from the distance sensory receptor around the acupoints via peripheral nerves and body fluid. In vivo recording the activities of stress reaction neurons (SRNs, CRH-like neurons) in hypothalamic paraventricular nucleus (PVN) in response to the stimulations from different acupoints could therefore objectively reflect the acupuncture afferent effect. In this study, the electrophysiological method was adopted to record synchronously the activities of 43 CRH-like neurons after acupuncture stimulations at 33 acupoints located at the different regions. The acupoints that specifically activate certain CRH-like neurons (specificity acupoints) were selected. Furthermore, we investigated in a rat model of unpredictable chronic mild stress (UCMS) whether these specificity acupoints regulate HPAA function. The endpoints of measurement include corticosterone (CORT) level in peripheral blood, the expressions of corticotrophin releasing hormone (CRH) and glucocorticoid receptor (GR) protein in PVN and the animal behavioral performance. Our results reveal that Shenshu (BL23), Ganshu (BL18), Qimen (LR14), Jingmen (GB25), Riyue (GB24), Zangmen (LR13), Dazui (DU14) and auricular concha region (ACR) are the specificity acupoints; and Gallbladder, Liver and Du Channels were the specificity Channels. The acupoints on Gallbladder Channel and the acupoints innervated by the same spinal cord segments as the adrenal gland demonstrated dramatic effects. This study provides a new platform to further explore acupoints specificity in the regulation of HPAA activities.

  12. Psoriasis severity and hypothalamic-pituitary-adrenal axis function: results from the CALIPSO study

    Directory of Open Access Journals (Sweden)

    A.R. Brunoni

    2014-12-01

    Full Text Available Psoriasis is a chronic inflammatory disease that significantly impacts life quality, being associated with stress and mental disorders. We investigated whether the activity of the hypothalamic-pituitary-adrenal (HPA axis was associated with psoriasis severity, daily life stress and anxiety, and depressive symptoms. In this ancillary study, which was part of the CALIPSO (coronary artery calcium in psoriasis study, saliva was collected from 102 patients with psoriasis immediately upon awakening, 30, and 60 min after awakening, at 2:00 pm and at bedtime (five time points to determine salivary cortisol levels. We used Pearson's correlation coefficient to evaluate the association of clinical and psychopathological variables with HPA activity. We found a direct correlation between bedtime cortisol and psoriasis severity evaluated by the psoriasis area severity index (PASI; r=0.39, P<0.001. No correlations between other clinical and psychopathological variables or with other cortisol assessments were observed. The findings indicated that HPA dysfunction may be present in psoriasis, as bedtime cortisol was correlated with psoriasis severity. Our study is limited by the lack of a control group; therefore, we were not able to explore whether these cortisol values were different compared with a concurrent, healthy sample.

  13. Hypothalamic-pituitary-adrenal (HPA) axis functioning in relation to body fat distribution.

    Science.gov (United States)

    Rutters, Femke; Nieuwenhuizen, Arie G; Lemmens, Sofie G T; Born, Jurriaan M; Westerterp-Plantenga, Margriet S

    2010-06-01

    To relate hypothalamic-pituitary-adrenal (HPA) axis functioning and HPA feedback functioning to body fat distribution in normal weight to obese subjects. 91 men and 103 women [age 18-45 years, BMI 19-35 kg/m(2), waist-to-hip ratio (WHR) 0.6-1.1]. Anthropometry, body composition using hydrodensitometry and deuterium dilution method, cortisol variability by measuring 5-h cortisol concentrations, HPA axis feedback functioning using a dexamethasone suppression test, and HPA axis functioning under a challenged condition consisting of a standardized high-intensity test with ingestion of 4 mg dexamethasone. In men, an inverse relationship was observed between 5-h cortisol exposure (nmol/ml) and fat mass index (FMI) (kg/m(2)) (r = -0.55, P < 0.001). In women, relationships were observed between 5-h cortisol exposure (nmol/ml.min) and WHR (r = -0.49, P < 0.001), maximal workload (r = 0.32, P < 0.001) as well as oral contraceptive use (r = 0.38, P < 0.001). Similarly, in men, an inverse relationship was observed between negative feedback expressed as baseline concentrations minus post dexamethasone cortisol concentrations (nmol/ml) and FMI (r = -0.53, P < 0.001). In women, relationships were observed between negative feedback expressed as baseline concentrations minus post dexamethasone cortisol concentrations (nmol/ml) and WHR (r = -0.43, P < 0.001), maximal workload (r = 0.30, P < 0.001) as well as oral contraceptive use (r = 0.43, P < 0.001) in women. Moreover, an inverse relationship was observed between HPA axis functioning in a challenged condition expressed as percentage increase of cortisol concentrations after standardized high-intensity test with ingestion of 4 mg dexamethasone (%) and waist circumference (r = -0.21, P < 0.10) in men and WHR (r = -0.21, P < 0.05) in women. In men, strong positive relationships were observed between FMI and waist circumference (r = 0.85, P < 0.001), as well as waist-to-hip ratio (r = 0.70, P < 0.001). Disturbance of HPA axis

  14. Child mortality, hypothalamic-pituitary-adrenal axis activity and cellular aging in mothers.

    Science.gov (United States)

    Barha, Cindy K; Salvante, Katrina G; Hanna, Courtney W; Wilson, Samantha L; Robinson, Wendy P; Altman, Rachel M; Nepomnaschy, Pablo A

    2017-01-01

    Psychological challenges, including traumatic events, have been hypothesized to increase the age-related pace of biological aging. Here we test the hypothesis that psychological challenges can affect the pace of telomere attrition, a marker of cellular aging, using data from an ongoing longitudinal-cohort study of Kaqchikel Mayan women living in a population with a high frequency of child mortality, a traumatic life event. Specifically, we evaluate the associations between child mortality, maternal telomere length and the mothers' hypothalamic-pituitary-adrenal axis (HPAA), or stress axis, activity. Child mortality data were collected in 2000 and 2013. HPAA activity was assessed by quantifying cortisol levels in first morning urinary specimens collected every other day for seven weeks in 2013. Telomere length (TL) was quantified using qPCR in 55 women from buccal specimens collected in 2013. Shorter TL with increasing age was only observed in women who experienced child mortality (p = 0.015). Women with higher average basal cortisol (p = 0.007) and greater within-individual variation (standard deviation) in basal cortisol (p = 0.053) presented shorter TL. Non-parametric bootstrapping to estimate mediation effects suggests that HPAA activity mediates the effect of child mortality on TL. Our results are, thus, consistent with the hypothesis that traumatic events can influence cellular aging and that HPAA activity may play a mediatory role. Future large-scale longitudinal studies are necessary to confirm our results and further explore the role of the HPAA in cellular aging, as well as to advance our understanding of the underlying mechanisms involved.

  15. Ketamine and Etomidate Down-regulate the Hypothalamic-Pituitary-Adrenal Axis in an Endotoxemic Mouse Model.

    Science.gov (United States)

    Besnier, Emmanuel; Clavier, Thomas; Tonon, Marie-Christine; Selim, Jean; Lefevre-Scelles, Antoine; Morin, Fabrice; Tamion, Fabienne; Dureuil, Bertrand; Castel, Hélène; Compere, Vincent

    2017-08-01

    We compared the effects of etomidate and ketamine on the hypothalamic-pituitary-adrenal axis during sepsis. Mice (n = 5/group) were injected intraperitoneally with lipopolysaccharide (10 mg/kg) and 6 h later randomized to receive ketamine (100 mg/kg), etomidate (30 mg/kg), or saline. At two time points (12 and 48 h), messenger RNA levels of hypothalamic corticotropin-releasing hormone, pituitary proopiomelanocortin, and four adrenal enzymes (P450 side-chain cleavage, 3β-hydroxysteroid deshydrogenase, 21-hydroxylase, and 11β-hydroxylase) were measured by in situ hybridization (results are presented as optical density), and plasma levels of corticosterone and adrenocorticotropin hormones were measured by enzyme-linked immunosorbent assay (mean ± SD). At 12 h, lipopolysaccharide induced an overexpression of corticotropin-releasing hormone (32 ± 5 vs. 18 ± 6, P ketamine reduced P450 side-chain cleavage (19 ± 7 and 19 ± 3 vs. 32 ± 4, P Ketamine also inhibited adrenocorticotropin hormone production (2.5 ± 3.6 vs. 36 ± 15 pg/ml, P Ketamine and etomidate did not modify corticosterone plasma levels. Our endotoxemic model induces an initial activation of the hypothalamic-pituitary-adrenal axis, followed by a secondary inhibition of adrenal steroidogenesis processes. Ketamine and etomidate inhibit the enzyme expression and activity of the adrenal gland at the early stage.

  16. Basal hypothalamic pituitary adrenal axis activity and hippocampal volumes: the SMART-Medea study.

    Science.gov (United States)

    Knoops, Arnoud J G; Gerritsen, Lotte; van der Graaf, Yolanda; Mali, Willem P Th M; Geerlings, Mirjam I

    2010-06-15

    It has frequently been hypothesized that high levels of glucocorticoids have deleterious effects on the hippocampus and increase risk for cognitive decline and dementia, but no large-scale studies in humans have examined the direct relation between hippocampal volumes and hypothalamic-pituitary-adrenal axis activity. Cross-sectional analyses within the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART)-Medea study, an ancillary study to the SMART-MR study on brain changes on magnetic resonance imaging (MRI) among patients with arterial disease. In 575 patients (mean age 62 +/- 9 years), diurnal cortisol rhythm was assessed with six saliva samples, collected at awakening; at 30, 45, and 60 min thereafter; and at 10 pm and 11 pm. A low dose of dexamethasone (.5 mg) was administered at 11 pm, and saliva was sampled the next morning at awakening. Volumetric measurements of the hippocampus were performed on a three-dimensional fast field echo T1-weighted scan with isotropic voxels. Mean total relative hippocampal volume was 6.0 +/- .7 mL. Linear regression analyses, adjusted for age, sex, vascular risk factors, and global brain atrophy showed that participants with higher evening levels and higher awakening levels after dexamethasone had smaller hippocampal volumes [B per SD (4.2) increase = -.09 mL; 95% confidence interval -.15 to -.03 mL and B per SD (2.5) increase = -.07 mL; 95% confidence interval -.13 to -.01 mL, respectively]. The awakening response was not significantly associated with hippocampal volumes. In this population, higher evening cortisol levels and reduced suppression after dexamethasone were associated with smaller hippocampal volumes, independent of total brain volume. The cortisol response after awakening was not associated with hippocampal volume.

  17. Evolutionary functions of early social modulation of hypothalamic-pituitary-adrenal axis development in humans.

    Science.gov (United States)

    Flinn, Mark V; Nepomnaschy, Pablo A; Muehlenbein, Michael P; Ponzi, Davide

    2011-06-01

    The hypothalamic-pituitary-adrenal axis (HPAA) is highly responsive to social challenges. Because stress hormones can have negative developmental and health consequences, this presents an evolutionary paradox: Why would natural selection have favored mechanisms that elevate stress hormone levels in response to psychosocial stimuli? Here we review the hypothesis that large brains, an extended childhood and intensive family care in humans are adaptations resulting from selective forces exerted by the increasingly complex and dynamic social and cultural environment that co-evolved with these traits. Variations in the modulation of stress responses mediated by specific HPAA characteristics (e.g., baseline cortisol levels, and changes in cortisol levels in response to challenges) are viewed as phenotypically plastic, ontogenetic responses to specific environmental signals. From this perspective, we discuss relations between physiological stress responses and life history trajectories, particularly the development of social competencies. We present brief summaries of data on hormones, indicators of morbidity and social environments from our long-term, naturalistic studies in both Guatemala and Dominica. Results indicate that difficult family environments and traumatic social events are associated with temporal elevations of cortisol, suppressed reproductive functioning and elevated morbidity. The long-term effects of traumatic early experiences on cortisol profiles are complex and indicate domain-specific effects, with normal recovery from physical stressors, but some heightened response to negative-affect social challenges. We consider these results to be consistent with the hypothesis that developmental programming of the HPAA and other neuroendocrine systems associated with stress responses may facilitate cognitive targeting of salient social challenges in specific environments. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. 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.

  19. DOWN-REGULATION OF THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS REDUCES BRAIN-DAMAGE AND NUMBER OF SEIZURES FOLLOWING HYPOXIA/ISCHAEMIA IN RATS

    NARCIS (Netherlands)

    KRUGERS, HJ; KNOLLEMA, S; KEMPER, RHA; TERHORST, GJ; KORF, J

    1995-01-01

    Several reports suggest that the activity of the hypothalamo-pituitary-adrenal axis (HPA-axis) is increased following hypoxia/ischaemia and that this might be associated with increased neuronal vulnerability. The main goal of this study was to examine the effects of down-regulation of the HPA-axis

  20. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  1. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  2. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  3. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  4. Ansiedade, pânico e o eixo hipotálamo-pituitária-adrenal Anxiety, panic and the hypothalamic-pituitary-adrenal axis

    Directory of Open Access Journals (Sweden)

    Frederico G Graeff

    2007-05-01

    Full Text Available OBJETIVO: Este artigo discute a ativação diferencial do eixo hipotálamo-pituitária-adrenal no transtorno de ansiedade generalizada e no transtorno de pânico. MÉTODO: Resultados de recentes revisões da literatura são resumidos e discutidos. RESULTADOS: Os resultados de estudos experimentais que dosaram o hormônio adrenocorticotrópico, o cortisol e a prolactina mostram que ataques de pânico naturais, bem como os provocados por agentes panicogênicos seletivos - como lactato de sódio e dióxido de carbono -, não ativam o eixo hipotálamo-pituitária-adrenal. Agonistas do receptor de colecistocinina do tipo B, como o peptídeo colecistocinina-4 e a pentagastrina, elevam os hormônios de estresse, independentemente da ocorrência de um ataque de pânico, parecendo ativar diretamente o eixo hipotálamo-pituitária-adrenal. O antagonista benzodiazepínico flumazenil não eleva o nível dos hormônios de estresse; porém, este agente farmacológico não induz ataques de pânico de modo consistente. Agentes farmacológicos que aumentam a ansiedade em pacientes de pânico (cafeína, ioimbina, agonistas serotonérgicos, assim como em pessoas saudáveis, elevam o nível dos hormônios de estresse. CONCLUSÕES: Além das diferenças na sintomatologia e na resposta farmacológica, o transtorno de ansiedade generalizada e o transtorno de pânico afetam os hormônios de estresse de modo distinto. Enquanto a ansiedade antecipatória e o transtorno de ansiedade generalizada ativam tanto o eixo hipotálamo-pituitária-adrenal como o simpático-adrenal, o ataque de pânico causa acentuada ativação simpática; porém, afeta pouco o eixo hipotálamo-pituitária-adrenal.OBJECTIVE: This article focuses on the differential activation of the hypothalamic-pituitary-adrenal axis in generalized anxiety disorder and panic disorder. METHOD: The results of recently reported reviews of the literature are summarized and discussed. RESULTS: The results of

  5. The hypothalamo-pituitary-adrenal (HPA) axis in sheep is attenuated during lactation in response to psychosocial and predator stress.

    Science.gov (United States)

    Ralph, C R; Tilbrook, A J

    2016-04-01

    Activation of the hypothalamo-pituitary-adrenal (HPA) axis by psychosocial stress is attenuated during lactation. We tested the hypothesis that lactating ewes will have attenuated HPA axis responses to isolation and restraint but will have greater responses to predator stress in the form of barking dogs. We imposed two 4 h stressors: psychosocial stress (isolation and restraint of ewes) and predator stress (barking dogs). Blood was collected intravenous every 10 min from nonlactating ewes (n = 6), lactating ewes with lambs present but not able to be suckled (n = 6), and lactating ewes with lambs present and able to be suckled (n = 6). Plasma cortisol and oxytocin were measured. For nonlactating ewes, cortisol increased (P HPA axis response to a stressor that may be perceived to threaten the welfare of themselves and/or their offspring. The role of oxytocin in attenuation of the HPA axis to stress in sheep is unclear from the current research and requires further investigation.

  6. Comparison of miRNA expression profiles in pituitary-adrenal axis between Beagle and Chinese Field dogs after chronic stress exposure.

    Science.gov (United States)

    Luo, Wei; Fang, Meixia; Xu, Haiping; Xing, Huijie; Fu, Jiangnan; Nie, Qinghua

    2016-01-01

    MicoRNAs (miRNAs), usually as gene regulators, participate in various biological processes, including stress responses. The hypothalamus-pituitary-adrenal axis (HPA axis) is an important pathway in regulating stress response. Although the mechanism that HPA axis regulates stress response has been basically revealed, the knowledge that miRNAs regulate stress response within HPA axis, still remains poor. The object of this study was to investigate the miRNAs in the pituitary and adrenal cortex that regulate chronic stress response with high-throughput sequencing. The pituitary and adrenal cortex of beagles and Chinese Field dogs (CFD) from a stress exposure group (including beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)) and a control group (including beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)), were selected for miRNA-seq comparisons. Comparisons, that were made in pituitary (including BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1 and BP2 vs. CFDP2) and adrenal cortex (including BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2), showed that a total of 39 and 18 common differentially expressed miRNAs (DE-miRNAs) (Total read counts > 1,000, Fold change > 2 & p-value 2 & p-value < 0.05) from those target genes in pituitary and adrenal cortex were obtained separately, in combination with our previous corresponding transcriptome study. Meanwhile, in line with that miRNAs usually negatively regulated their target genes and the dual luciferase reporter assay, we finally identified cfa-miR-205 might play an important role by upregulating MMD in pituitary and hippocampus, thus enhancing the immune response, under chronic stress exposure. Our results shed light on the miRNA expression profiles in the pituitary and adrenal cortex with and without chronic stress exposure, and provide a new insight into miR-205 with its

  7. Skin under the (Spot)-Light: Cross-Talk with the Central Hypothalamic-Pituitary-Adrenal (HPA) Axis.

    Science.gov (United States)

    Jozic, Ivan; Stojadinovic, Olivera; Kirsner, Robert S F; Tomic-Canic, Marjana

    2015-06-01

    UV radiation is among the most prevalent stressors in humans and diurnal rodents, exerting direct and indirect DNA damage, free-radical production, and interaction with specific chromophores that affects numerous biological processes. In addition to its panoply of effects, UVB (290-320 nm) radiation can specifically affect various local neuroendocrine activities by stimulating the expression of corticotropin-releasing hormone (CRH), urocortin, proopiomelanocortin (POMC), and POMC-derived peptides. Although very little is known about the interplay between the central hypothalamic-pituitary-adrenal (HPA) axis and the skin HPA axis analog, in the current issue Skobowiat and Slominski propose a novel mechanism by which exposure to UVB activates a local HPA axis in skin, which in turn activates the central HPA axis, with the requirement of a functional pituitary gland. This is the first evidence of the local HPA axis in skin contributing to the central neuroendocrine response. This raises intriguing possibilities regarding how local production of cortisol and other HPA axis molecules in skin influence overall systemic levels of cortisol and help regulate local and central HPA axes in the context of homeostasis, skin injury, and inflammatory skin disorders.

  8. Neuroanatomy and physiology of the avian hypothalamic/pituitary axis: clinical aspects.

    Science.gov (United States)

    Ritchie, Midge

    2014-01-01

    This article describes the anatomy of the avian hypothalamic/pituitary axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the somatotrophic axis, and neurohypophysis.

  9. Transcriptome comparison in the pituitary-adrenal axis between Beagle and Chinese Field dogs after chronic stress exposure.

    Science.gov (United States)

    Luo, Wei; Fang, Meixia; Xu, Haiping; Xing, Huijie; Nie, Qinghua

    2015-10-01

    Chronic stress can induce a series of maladjustments, and the response to stress is partly regulated by the hypothalamus-pituitary-adrenal axis. The aim of this study was to investigate the genetic mechanisms of this axis regulating stress responsiveness. The pituitary and adrenal cortex of Beagle and Chinese Field Dog (CFD) from a stress exposure group [including Beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), Beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)] and a control group [including Beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), Beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)], selected to perform RNA-seq transcriptome comparisons, showed that 40, 346, 376, 69, 70, 38, 57 and 71 differentially expressed genes were detected in BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1, BP2 vs. CFDP2, BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2 respectively. NPB was a gene common to BAC1 vs. BAC2 and CFDAC1 vs. CFDAC2, indicating it was a potential gene affecting response to chronic stress, regardless of the extent of chronic stress induced. PLP1 was a gene common to BP1 vs. CFDP1 and BP2 vs. CFDP2, suggesting its important roles in affecting the stress-tolerance difference between the two breeds, regardless of whether there was stress exposure or not. Pathway analysis found 12, 4, 11 and 1 enriched pathway in the comparisons of BP1 vs. CFDP1, BP2 vs. CFDP2, CFDP1 vs. CFDP2 and BAC1 vs. BAC2 respectively. Glutamatergic synapse, neuroactive ligand-receptor interaction, retrograde endocannabinoid signaling, GABAergic synapse, calcium signaling pathway and dopaminergic synapse were the most significantly enriched pathways in both CFDP1 vs. CFDP2 and BP1 vs. CFDP1. GO, KEGG pathway and gene network analysis demonstrated that GRIA3, GRIN2A, GRIN2B and NPY were important in regulating the stress response in CFD. Nevertheless, ADORA1, CAMK2A, GRM1, GRM7 and NR4A1 might be critical genes contributing to the stress

  10. Can Variation in Hypothalamic-Pituitary-Adrenal (HPA)-Axis Activity Explain the Relationship between Depression and Cognition in Bipolar Patients?

    NARCIS (Netherlands)

    van der Werf-Eldering, MJ; Riemersma-van der Lek, RF; Burger, H.; Holthausen, E.A.E.; Aleman, A.; Nolen, W.A.

    2012-01-01

    Background: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning. Method

  11. Caffeine-induced activated glucocorticoid metabolism in the hippocampus causes hypothalamic-pituitary-adrenal axis inhibition in fetal rats.

    Science.gov (United States)

    Xu, Dan; Zhang, Benjian; Liang, Gai; Ping, Jie; Kou, Hao; Li, Xiaojun; Xiong, Jie; Hu, Dongcai; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-01-01

    Epidemiological investigations have shown that fetuses with intrauterine growth retardation (IUGR) are susceptible to adult metabolic syndrome. Clinical investigations and experiments have demonstrated that caffeine is a definite inducer of IUGR, as children who ingest caffeine-containing food or drinks are highly susceptible to adult obesity and hypertension. Our goals for this study were to investigate the effect of prenatal caffeine ingestion on the functional development of the fetal hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis and to clarify an intrauterine HPA axis-associated neuroendocrine alteration induced by caffeine. Pregnant Wistar rats were intragastrically administered 20, 60, and 180 mg/kg · d caffeine from gestational days 11-20. The results show that prenatal caffeine ingestion significantly decreased the expression of fetal hypothalamus corticotrophin-releasing hormone. The fetal adrenal cortex changed into slight and the expression of fetal adrenal steroid acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc), as well as the level of fetal adrenal endogenous corticosterone (CORT), were all significantly decreased after caffeine treatment. Moreover, caffeine ingestion significantly increased the levels of maternal and fetal blood CORT and decreased the expression of placental 11β-hydroxysteroid dehydrogenase-2 (11β-HSD-2). Additionally, both in vivo and in vitro studies show that caffeine can downregulate the expression of fetal hippocampal 11β-HSD-2, promote the expression of 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor (GR), and enhance DNA methylation within the hippocampal 11β-HSD-2 promoter. These results suggest that prenatal caffeine ingestion inhibits the development of the fetal HPA axis, which may be associated with the fetal overexposure to maternal glucocorticoid and activated glucocorticoid metabolism in the fetal hippocampus. These results will be beneficial in

  12. Chronic administration of U50,488H fails to produce hypothalamo-pituitary-adrenal axis tolerance in neonatal rats.

    Science.gov (United States)

    Ignar, D M; Windh, R T; Kuhn, C M

    1992-02-01

    The present study investigated the effect of chronic administration of a kappa opioid receptor agonist on the function of kappa and mu opioid, serotonergic and cholinergic regulation of secretion from the hypothalamo-pituitary-adrenal axis in neonatal rats. After chronic treatment with saline or U50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]- benzeneacetamide methane sulfonate), a kappa opioid receptor agonist and subsequent pharmacological challenge, corticosterone (CS) in serum was determined. Kappa tolerance did not develop in pups treated on postnatal days 5-9 with increasing doses of U50,488H (0.5-2.5 mg/kg). When the rats were treated with the same chronic regimen of U50,488H at different stages of development from birth through weaning, only weanling rats became tolerant to U50,488H. In the absence of measurable kappa tolerance, the responses of corticosterone in serum to morphine, quipazine, a serotonin receptor agonist and physostigmine, an inhibitor of acetylcholinesterase, were attenuated in neonatal rats, treated with U50,488H. These studies suggest that kappa tolerance is more difficult to induce in developing rats than in adults and that regulation of the function of the hypothalamo-pituitary-adrenal axis by other neurotransmitter systems is altered by treatment with kappa opioid receptor agonists, even in the apparent absence of tolerance.

  13. 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...

  14. Involvement of the hypothalamic-pituitary-thyroid axis and its interaction with the hypothalamic-pituitary-adrenal axis in the ontogeny of avian thermoregulation: a review

    NARCIS (Netherlands)

    Debonne, M.; Baarendse, P.J.J.; Brand, van den H.; Kemp, B.; Bruggeman, V.; Decuypere, E.

    2008-01-01

    The emergence of thermoregulation in avian species is a complex matter in which neural as well as hormonal processes are involved. In a previous paper, the neural aspects of primary avian thermoregulation were discussed. In this paper the role of the hypothalamus-pituitary-thyroid axis (HPT-axis)

  15. Effect of cortisol infusion on the pituitary-adrenal axis of the hypothalamo-pituitary-disconnected fetal sheep.

    Science.gov (United States)

    Antolovich, G C; McMillen, I C; Robinson, P M; Silver, M; Young, I R; Perry, R A

    1992-09-01

    In order to determine whether cortisol acts directly at the level of the fetal pituitary to promote pars distalis corticotroph maturation, we have infused cortisol into the hypothalamo-pituitary-disconnected (HPD) fetal sheep from 111 to 117 days of gestation. In this study we have measured fetal plasma cortisol and immunoreactive adrenocorticotrophic hormone (ir-ACTH) concentrations between 105 and 116 days of gestation, and we have determined the proportions of adult- and fetal-type corticotrophs in the pars distalis of catheter control fetuses and in HPD fetuses infused with either saline (HPD+SAL) or cortisol (2 mg/day; HPD+F). The fetal plasma cortisol concentrations did not change significantly following HPD. The mean fetal plasma cortisol concentration between 113 and 116 days was threefold higher in the HPD+F fetuses than that measured in HPD fetuses. Following HPD, fetal plasma ir-ACTH concentrations were significantly higher than in catheter control fetuses. Despite the significant elevation in plasma cortisol concentrations in HPD+F fetuses between 113 and 116 days, plasma ir-ACTH concentrations were not different in these fetuses from HPD fetuses infused with saline. At 117 days of gestation in HPD+F fetuses, the proportion of fetal-type corticotrophs in the pars distalis was significantly less than in the HPD+SAL fetuses; however, there was no significant change in the proportion of adult-type corticotrophs in the pars distalis following cortisol infusion. We have shown that cortisol has a direct trophic effect on the maturation of the pars distalis corticotrophs; however, the full maturation of these cells requires an intact hypothalamo-pituitary axis. These findings demonstrate the importance of the fetal hypothalamus in anterior pituitary corticotroph maturation during the last third of gestation.

  16. Cranial irradiation modulates hypothalamic-pituitary-adrenal axis activity and corticosteroid receptor expression in the hippocampus of juvenile rat.

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    Velickovic, Natasa; Djordjevic, Ana; Drakulic, Dunja; Stanojevic, Ivana; Secerov, Bojana; Horvat, Anica

    2009-01-01

    Glucocorticoids, essential for normal hypothalamic-pituitary-adrenal (HPA) axis activity, exert their action on the hippocampus through two types of corticosteroid receptors: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Recent studies report that exposure of juvenile rats to cranial irradiation adversely affects HPA axis stability leading to its activation along with radiation- induced inflammation. This study was aimed to examine the acute effects of radiation on HPA axis activity and hippocampal corticosteroid receptor expression in 18-day-old rats. Since immobilization was part of irradiation procedure, both irradiated and sham-irradiated animals were exposed to this unavoidable stress. Our results demonstrate that the irradiated rats exhibited different pattern of corticosteroid receptor expression and hormone levels compared to respective controls. These differences included upregulation of GR protein in the hippocampus with a concomitant elevation of GR mRNA and an increase in circulating level of corticosterone. In addition, the expression of MR, both at the level of protein and gene expression, was not altered. Taken together, this study demonstrates that cranial irradiation in juvenile rats leads to enhanced HPA axis activity and increased relative GR/MR ratio in hippocampus. The present paper intends to show that neuroendocrine response of normal brain tissue to localized irradiation comprise both activation of HPA axis and altered corticosteroid receptor balance, probably as consequence of innate immune activation.

  17. Fatty acid metabolism and its longitudinal relationship with the hypothalamic-pituitary-adrenal axis in major depression : Associations with prospective antidepressant response

    NARCIS (Netherlands)

    Mocking, Roel J. T.; Verburg, Hanka F.; Westerink, Anne M.; Assies, Johanna; Vaz, Frederic M.; Koeter, Maarten W. J.; Ruhe, Henricus G.; Schene, Aart H.

    2015-01-01

    Background: Metabolism of dietary fatty acids (FAs), and its relationship with the hypothalamic-pituitary-adrenal (HPA)-axis, have been found to be altered in major depressive disorder (MDD). Moreover, indications exist that these factors are associated with antidepressant-response. If we better und

  18. Effects of high fat diet on the basal activity of the hypothalamus- pituitary-adrenal axis in mice: A systematic review

    NARCIS (Netherlands)

    Auvinen, H.E.; Romijn, J.A.; Biermasz, N.R.; Havekes, L.M.; Smit, J.W.A.; Rensen, P.C.N.; Pereira, A.M.

    2011-01-01

    Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the

  19. Effects of high fat diet on the basal activity of the hypothalamus- pituitary-adrenal axis in mice: A systematic review

    NARCIS (Netherlands)

    Auvinen, H.E.; Romijn, J.A.; Biermasz, N.R.; Havekes, L.M.; Smit, J.W.A.; Rensen, P.C.N.; Pereira, A.M.

    2011-01-01

    Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the

  20. Childhood adversity and allostatic overload of the hypothalamic-pituitary-adrenal axis: a vulnerability model for depressive disorders.

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    Wilkinson, Paul O; Goodyer, Ian M

    2011-11-01

    Childhood adversity is associated with increased risk for onset of depressive episodes. This review will present evidence that allostatic overload of the hypothalamic-pituitary-adrenal axis (HPAA) partially mediates this association. The HPAA is the physiological system that regulates levels of the stress hormone cortisol. First, data from animals and humans has shown that early environmental adversity is associated with long-term dysregulation of the HPAA. This may occur due to permanent epigenetic modification of the glucocorticoid receptor. Second, data from humans has demonstrated that HPAA dysregulation is associated with increased risk of future depression onset in healthy individuals, and pharmacological correction of HPAA dysregulation reduces depressive symptoms. HPAA dysregulation may result in corticoid-mediated abnormalities in neurogenesis in early life and/or neurotoxicity on neural systems that subserve emotion and cognition.

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

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    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

  2. Effects of corticotropin-releasing factor 1 receptor antagonism on the hypothalamic-pituitary-adrenal axis of rodents.

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    Gehlert, Donald R; Cramer, Jeffrey; Morin, S Michelle

    2012-06-01

    Corticotropin-releasing factor (CRF) is the major hypothalamic neuropeptide responsible for stimulation of the hypothalamic-pituitary-adrenal axis (HPAA), resulting in the synthesis and release of glucocorticoids from the adrenal cortex. In a recent study, we reported the discovery of the CRF1 receptor antagonist, 3-(4-chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (MTIP), which has efficacy in preclinical models of stress-induced alcohol consumption. Because CRF1 is important in HPAA activation, we evaluated the effects of MTIP administration on rodent HPAA function. Initial studies established the MTIP doses required for brain and pituitary CRF1 occupancy and those associated with the inhibition of intracerebroventricular CRF on the HPAA in mice. Then, rat basal plasma corticosterone (CORT) concentrations were measured hourly by radioimmunoassay for 24 h after three daily doses of MTIP or vehicle. In these studies, the early phase of the nocturnal CORT surge was reduced; however, the area under the CORT curve was identical for the 24-h period. In subsequent studies, increases in plasma CORT due to direct pharmacological manipulation of the HPAA axis or by stressors were evaluated after MTIP treatment in mice. MTIP attenuated CORT responses generated by immediate bolus administration of insulin or ethanol; however, MTIP did not affect activation of the HPAA by other stressors and pharmacological agents. Therefore, MTIP can modulate basal HPAA activity during the CORT surge and reduced activation after a select number of stressors but does not produce a lasting suppression of basal CORT. The ability of MTIP to modulate plasma CORT after hyperinsulinemia may provide a surrogate strategy for a target occupancy biomarker.

  3. Inflammatory airway features and hypothalamic-pituitary adrenal axis function in asthmatic rats combined with chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    CAI Cui; CAO Yu-xue; ZHANG Hong-ying; LE Jing-jing; DONG Jing-cheng; CUI Yan; XU Chang-qing; LIU Bao-jun; WU Jin-feng; DUAN Xiao-hong

    2010-01-01

    Background Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are both inflammatory airway diseases with different characteristics. However, there are many patients who suffer from both BA and COPD. This study was to evaluate changes of inflammatory airway features and hypothalamic-pituitary-adrenal (HPA) axis function in asthmatic rats combined with COPD.Methods Brown Norway (BN) rats were used to model the inflammatory airway diseases of BA, COPD and COPD+BA.These three models were compared and evaluated with respect to clinical symptoms, pulmonary histopathology, airway hyperresponsiveness (AHR), inflammatory cytokines and HPA axis function.Results The inflammatory airway features and HPA axis function in rats in the COPD+BA model group were greatly influenced. Rats in this model group showed features of the inflammatory diseases BA and COPD. The expression of inflammatory cytokines in this model group might be up or downregulated when both disease processes are present. The levels of corticotrophin releasing hormone mRNA and corticosterone in this model group were both significantly decreased than those in the control group (P <0.05).Conclusions BN rat can be used as an animal model of COPD+BA. By evaluating this animal model we found that the features of inflammation in rats in this model group seem to be exaggerated. The HPA axis functions in rats in this model group have been disturbed or impaired, which is prominent at the hypothalamic level.

  4. Total Flavonoids Extracted from Xiaobuxin-Tang on the Hyperactivity of Hypothalamic-Pituitary-Adrenal Axis in Chronically Stressed Rats

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    Lei An

    2011-01-01

    Full Text Available Our previous studies have demonstrated that the total flavonoids (XBXT-2 isolated from the extract of Xiaobuxin-Tang (XBXT, a traditional Chinese herbal decoction, ameliorated behavioral alterations and hippocampal dysfunctions in chronically stressed rats. Studies over the last decades have suggested that the hyperactivity of hypothalamic-pituitary-adrenal (HPA axis is one of the most consistent findings in stress-related depression. Herein, we used the same chronic mild stress model of rats as before to further investigate the effect of XBXT-2 on the hyperactivity of HPA axis, including the stress hormones levels and glucocorticoid receptors (GRs expression. Our ELISA results showed that chronic administration of XBXT-2 (25, 50 mg kg−1, p.o., 28 days, the effective doses for behavioral responses significantly decreased serum corticosterone level and its upstream stress hormone adrenocorticotropic hormone (ACTH level in chronically stressed rats. Furthermore, western blotting result demonstrated XBXT-2 treatment ameliorated stress-induced decrease of GRs expression in hippocampus, an important target involved in the hyperactivity of HPA axis. These results were similar to that of classic antidepressant imipramine treatment (10 mg kg−1, p.o.. In conclusion, the modulation of HPA axis produced by XBXT-2, including the inhibition of stress hormones levels and up-regulation of hippocampal GRs expression, may be an important mechanism underlying its antidepressant-like effect in chronically stressed rats.

  5. Investigating the effect of acute sleep deprivation on hypothalamic-pituitary-adrenal-axis response to a psychosocial stressor.

    Science.gov (United States)

    Vargas, Ivan; Lopez-Duran, Nestor

    2017-05-01

    The hypothalamic-pituitary-adrenal (HPA) axis has been previously identified as one potential mechanism that may explain the link between sleep deprivation and negative health outcomes. However, few studies have examined the direct association between sleep deprivation and HPA-axis functioning, particularly in the context of stress. Therefore, the aim of the current study was to investigate the relationship between acute sleep deprivation and HPA-axis reactivity to a psychosocial stressor. Participants included 40 healthy, young adults between the ages of 18-29. The current protocol included spending two nights in the laboratory. After an adaptation night (night 1), participants were randomized into either a sleep deprivation condition (29 consecutive hours awake) or a control condition (night 2). Following the second night, all participants completed the Trier Social Stress Test (TSST). Salivary cortisol was collected before, during, and after the TSST. Results indicated that there were significant group differences in cortisol stress reactivity. Specifically, compared to participants in the control condition, participants in the sleep deprivation condition had greater baseline (i.e., pre-stress) cortisol, yet a blunted cortisol response to the TSST. Taken together, a combination of elevated baseline cortisol (and its subsequent effect on HPA-axis regulatory processes) and a relative 'ceiling' on the amount of cortisol a laboratory stressor can produce may explain why participants in the sleep deprivation condition demonstrated blunted cortisol responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Sleep apnoea and the hypothalamic-pituitary-adrenal axis in men and women: effects of continuous positive airway pressure.

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    Kritikou, Ilia; Basta, Maria; Vgontzas, Alexandros N; Pejovic, Slobodanka; Fernandez-Mendoza, Julio; Liao, Duanping; Bixler, Edward O; Gaines, Jordan; Chrousos, George P

    2016-02-01

    Previous findings on the association of obstructive sleep apnoea (OSA) and the hypothalamic-pituitary-adrenal (HPA) axis are inconsistent, partly due to the confounding effect of obesity and infrequent sampling. Our goal was to examine whether in a relatively nonobese population, OSA is associated with elevated cortisol levels and to assess the effects of a 2-month placebo-controlled continuous positive airway pressure (sham-CPAP) use.72 subjects (35 middle-aged males and post-menopausal females with OSA, and 37 male and female controls) were studied in the sleep laboratory for four nights. 24-h blood sampling was performed every hour on the fourth day and night in the sleep laboratory at baseline, after sham-CPAP and after CPAP treatment.In both apnoeic men and women, OSA was associated with significantly higher 24-h cortisol levels compared with controls, whereas CPAP lowered cortisol levels significantly, close to those of controls.These results suggest that OSA in nonobese men and slightly obese women is associated with HPA axis activation, similar albeit stronger compared with obese individuals with sleep apnoea. Short-term CPAP use decreased cortisol levels significantly compared with baseline, indicating that CPAP may have a protective effect against comorbidities frequently associated with chronic activation of the HPA axis, e.g. hypertension.

  7. Regulation of 5-HT receptors and the hypothalamic-pituitary-adrenal axis. Implications for the neurobiology of suicide.

    Science.gov (United States)

    López, J F; Vázquez, D M; Chalmers, D T; Watson, S J

    1997-12-29

    Disturbances in the serotonin (5-HT) system is the neurobiological abnormality most consistently associated with suicide. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is also described in suicide victims. The HPA axis is the classical neuroendocrine system that responds to stress and whose final product, corticosteroids, targets components of the limbic system, particularly the hippocampus. We will review results from animal studies that point to the possibility that many of the 5-HT receptor changes observed in suicide brains may be a result of, or may be worsened by, the HPA overactivity that may be present in some suicide victims. The results of these studies can be summarized as follows: (1) chronic unpredictable stress produces high corticosteroid levels in rats; (2) chronic stress also results in changes in specific 5-HT receptors (increases in cortical 5-HT2A and decreases in hipocampal 5-HT1A and 5-HT1B); (3) chronic antidepressant administration prevents many of the 5-HT receptor changes observed after stress; and (4) chronic antidepressant administration reverses the overactivity of the HPA axis. If indeed 5-HT receptors have a partial role in controlling affective states, then their modulation by corticosteroids provides a potential mechanism by which these hormones may regulate mood. These data may also provide a biological understanding of how stressful events may increase the risk for suicide in vulnerable individuals and may help us elucidate the neurobiological underpinnings of treatment resistance.

  8. Expression of genes related to the hypothalamic-pituitary-adrenal axis in murine fetal lungs in late gestation

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    Côté Mélissa

    2010-11-01

    Full Text Available Abstract Background Lung maturation is modulated by several factors, including glucocorticoids. Expression of hypothalamic-pituitary-adrenal (HPA axis-related components, with proposed or described local regulatory systems analogous to the HPA axis, was reported in peripheral tissues. Here, HPA axis-related genes were studied in the mouse developing lung during a period overlapping the surge of surfactant production. Methods Expression of genes encoding for corticotropin-releasing hormone (CRH, CRH receptors (CRHR 1 and 2beta, CRH-binding protein, proopiomelanocortin (POMC, melanocortin receptor 2 (MC2R, and glucocorticoid receptor was quantified by real-time PCR and localized by in situ hydridization in fetal lungs at gestational days (GD 15.5, 16.5, and 17.5, and was also quantified in primary mesenchymal- and epithelial cell-enriched cultures. In addition, the capability of CRH and adrenocorticotropic hormone (ACTH to stimulate pulmonary expression of enzymes involved in the adrenal pathway of glucocorticoid synthesis was addressed, as well as the glucocorticoid production by fetal lung explants. Results We report that all the studied genes are expressed in fetal lungs according to different patterns. On GD 15.5, Mc2r showed peaks in expression in samples that have previously presented high mRNA levels for glucocorticoid synthesizing enzymes, including 11beta-hydroxylase (Cyp11b1. Crhr1 mRNA co-localized with Pomc mRNA in cells surrounding the proximal epithelium on GD 15.5 and 16.5. A transition in expression sites toward distal epithelial cells was observed between GD 15.5 and 17.5 for all the studied genes. CRH or ACTH stimulation of genes involved in the adrenal pathway of glucocorticoid synthesis was not observed in lung explants on GD 15.5, whereas CRH significantly increased expression of 21-hydroxylase (Cyp21a1 on GD 17.5. A deoxycorticosterone production by fetal lung explants was observed. Conclusions Temporal and spatial

  9. Hypothalamic-pituitary adrenal (HPAA) axis function in adult Fischer-344 rats exposed during development to neurotoxic chemicals perinatally.

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    Rosecrans, J A; Johnson, J H; Tilson, H A; Hong, J S

    1984-01-01

    The major objective of these experiments was to determine long-term effects on the hypothalamic-pituitary adrenal axis (HPAA) of adult rats exposed during development to chlordecone, an organochlorine insecticide. Chlordecone was administered to mothers prenatally plus the first 12 days of the neonatal period (6 ppm in the diet) or neonatally via a single subcutaneous injection to rats at 4 days of age (1 mg/pup in 20 micrograms of DMSO). DMSO (20 microliters/pup) and dexamethasone (100 micrograms/pup in 20 microliters saline) were also injected on day 4. HPAA function was evaluated at 70-80 days of age. Responsiveness of the HPAA to a repeated stressor was evaluated by exposing rats of each treatment group to a 7-day stress-induced analgesia (SIA) paradigm consisting of a daily 15 sec foot-shock (0.9 mA) exposure which was preceded by a 15 sec white noise conditioned stimulus. The behavioral response to daily stress was evaluated by measuring tail-flick latencies immediately before and/or after each stress exposure. The conditioned response to stress was evaluated 24 hours after the last of 7 daily foot-shock sessions in which rats of each treatment and experimental group were exposed to the shock chamber only. All rats were killed 15 minutes after the final session and tissue (serum and adrenals) were removed and frozen for later chemical analysis; serum and adrenal corticosterone (CS) and serum prolactin (Prl) levels were measured. Perinatal exposure to chlordecone did not significantly alter the behavioral and/or neuroendocrine responses to stress. Ambient hormone levels (both CS and Prl), however, were uniformly attenuated by chlordecone.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Effects of specific mu and kappa opiate tolerance and abstinence on hypothalamo-pituitary-adrenal axis secretion in the rat.

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    Ignar, D M; Kuhn, C M

    1990-12-01

    Chronic administration of opiates to rats results in HPA axis tolerance and abstinence-induced hypersecretion. The effects of specific mu and kappa tolerance and withdrawal on the functional secretion of the HPA axis were evaluated in this study. Adult male rats were injected s.c. twice daily with saline, morphine or U50,488 for 5 days. Serum adrenocorticotrophic hormone (ACTH) or corticosterone (CS) were determined by radioimmunoassay as measures of HPA axis function. Tolerance to morphine (10 mg/kg) and U50,488 (1 mg/kg), but no cross-tolerance, was observed suggesting the development of mu- or kappa-specific tolerance, respectively. Tolerance does not occur at the pituitary or adrenal levels after these paradigms because ACTH and CS responses to exogenous corticotropin-releasing factor and ACTH, respectively, were not attenuated. CS secretion in response to novelty stress was not affected by either chronic opiate treatment, but the circadian variation of CS levels was slightly blunted after chronic morphine. In contrast, the elevation of CS secretion by quipazine (0.5 mg/kg) and physostigmine (0.1 mg/kg) was attenuated after chronic U50,488, but not morphine administration. Both spontaneous and antagonist-precipitated withdrawal from morphine, but not U50,488, resulted in elevation of CS levels. Low doses of morphine suppressed morphine abstinence-induced CS hypersecretion, whereas, U50,488 and clonidine had no effect. In conclusion, alterations of HPA axis function occur during chronic mu or kappa opiate administration that are receptor-specific and involve multiple neural controls of the HPA axis.

  11. Effects of nutritional stress during different developmental periods on song and the hypothalamic-pituitary-adrenal axis in zebra finches.

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    Kriengwatana, B; Wada, H; Schmidt, K L; Taves, M D; Soma, K K; MacDougall-Shackleton, S A

    2014-03-01

    In songbirds, developmental stress affects song learning and production. Altered hypothalamic-pituitary-adrenal (HPA) axis function resulting in elevated corticosterone (CORT) may contribute to this effect. We examined whether developmental conditions affected the association between adult song and HPA axis function, and whether nutritional stress before and after nutritional independence has distinct effects on song learning and/or vocal performance. Zebra finches (Taeniopygia guttata) were raised in consistently high (HH) or low (LL) food conditions until post-hatch day (PHD) 62, or were switched from high to low conditions (HL) or vice versa (LH) at PHD 34. Song was recorded in adulthood. We assessed the response of CORT to handling during development and to dexamethasone (DEX) and adrenocorticotropic hormone (ACTH) challenges during adulthood. Song learning and vocal performance were not affected by nutritional stress at either developmental stage. Nutritional stress elevated baseline CORT during development. Nutritional stress also increased rate of CORT secretion in birds that experienced stress only in the juvenile phase (HL group). Birds in the LL group had lower CORT levels after injection of ACTH compared to the other groups, however there was no effect of nutritional stress on the response to DEX. Thus, our findings indicate that developmental stress can affect HPA function without concurrently affecting song.

  12. 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.

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

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    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

  14. Short periods of prenatal stress affect growth, behaviour and hypothalamo-pituitary-adrenal axis activity in male guinea pig offspring.

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    Kapoor, Amita; Matthews, Stephen G

    2005-08-01

    Prenatal stress can have profound long-term influences on physiological function throughout the course of life. We hypothesized that focused periods of moderate prenatal stress at discrete time points in late gestation have differential effects on hypothalamo-pituitary-adrenal (HPA) axis function in adult guinea pig offspring, and that changes in HPA axis function will be associated with modification of anxiety-related behaviour. Pregnant guinea pigs were exposed to a strobe light for 2 h on gestational days (GD) 50, 51, 52 (PS50) or 60, 61, 62 (PS60) (gestation length approximately 70 days). A control group was left undisturbed throughout pregnancy. Behaviour was assessed in male offspring on postnatal day (PND)25 and PND70 by measurement of ambulatory activity and thigmotaxis (wall-seeking behaviour) in a novel open field environment. Subsequent to behavioural testing, male offspring were cannulated (PND75) to evaluate basal and activated HPA axis function. Body weight was significantly decreased in adult PS50 and PS60 offspring and this effect was apparent soon after weaning. The brain-to-body-weight ratio was significantly increased in adult PS50 males. Basal plasma cortisol levels were elevated in PS50 male offspring throughout the 24 h sampling period compared with controls. In response to an ACTH challenge and to exposure to an acute stressor, PS60 male offspring exhibited elevated plasma cortisol responses. Plasma testosterone concentrations were strikingly decreased in PS50 offspring. Thigmotaxis in the novel environment was increased in PS50 male offspring at PND25 and PND70, suggesting increased anxiety in these animals. In conclusion, prenatal stress during critical windows of neuroendocrine development programs growth, HPA axis function, and stress-related behaviour in adult male guinea pig offspring. Further, the nature of the effect is dependant on the timing of the maternal stress during pregnancy.

  15. 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.

  16. Hypothalamo-pituitary adrenal axis and sympatho-adrenal medullary system responses to psychological stress were not attenuated in women with elevated physical fitness levels.

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    Jayasinghe, Sisitha U; Lambert, Gavin W; Torres, Susan J; Fraser, Steve F; Eikelis, Nina; Turner, Anne I

    2016-02-01

    It is not clear if higher levels of cardiorespiratory fitness are associated with lower hypothalamo-pituitary adrenal (HPA) axis and sympatho-adrenal medullary (SAM) system reactivity to psychological stress in women. The association between cardio-metabolic risk markers and acute physiological responses to psychological stress in women who differ in their cardiorespiratory fitness status has also not been investigated. Women with high (n = 22) and low (n = 22) levels of fitness aged 30-50 years (in the mid-follicular phase of the menstrual cycle) were subjected to a Trier Social Stress Test (TSST) at 1500 h. Plasma concentrations of cortisol, adrenaline (Adr), noradrenaline (NA), and dopamine (DA) were measured in samples collected every 7-15 min from 1400 to 1700 h. Heart rate and blood pressure were measured at the same time points. Low-fit women had elevated serum triglyceride, cholesterol/HDL ratio, fasting glucose, and HOMA-IR levels compared with high-fit women. While cortisol, Adr, NA, HR, and blood pressure all demonstrated a significant response to the TSST, the responses of these variables did not differ significantly between high- and low-fit women in response to the TSST. Dopamine reactivity was significantly higher in the low-fit women compared with high-fit women. There was also a significant negative correlation between VO2 max and DA reactivity. These findings suggest that, for low-fit women aged 30-50 years, the response of HPA axis and SAM system to a potent acute psychological stressor is not compromised compared to that in high-fit women.

  17. Pre-receptor Regulation of Cortisol in Hypothalamic-Pituitary-Adrenal Axis Functioning an Metabolism

    NARCIS (Netherlands)

    M.J.H.J. Dekker (Marieke)

    2011-01-01

    textabstractGlucocorticoids (GCs) are ubiquitous, nuclear hormones, which are essential for life. In man, the main GC is cortisol, produced by the adrenals, endocrine glands that are situated on top of the kidneys. Cortisol exerts its functions in nearly all tissues and is crucial in the mediation o

  18. Cortisol reactivity and suicidal behavior: investigating the role of hypothalamic-pituitary-adrenal axis responses to stress in suicide attempters and ideators

    OpenAIRE

    O'Connor, Daryl B.; Green, Jessica A.; Ferguson, Eamonn; O'Carroll, Ronan E.; O'Connor, Rory C.

    2017-01-01

    Every 40 s a person dies by suicide somewhere in the world. The causes of suicidal behavior are not fully understood. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, is one potential risk factor. The current study aimed to investigate whether cortisol reactivity to a laboratory stress task differentiated individuals who had previously made a suicide attempt from those who had thought about suicide (suicide ideators) and control participants. On...

  19. Cortisol reactivity and suicidal behavior: investigating the role of hypothalamic-pituitary-adrenal axis responses to stress in suicide attempters and ideators

    OpenAIRE

    O’Connor, Daryl B.; Green, Jessica A.; Ferguson, Eamonn; O’Carroll, Ronan E.; O’Connor, Rory C

    2017-01-01

    Every 40 seconds a person dies by suicide somewhere in the world. The causes of suicidal behavior are not fully understood. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, is one potential risk factor. The current study aimed to investigate whether cortisol reactivity to a laboratory stress task differentiated individuals who had previously made a suicide attempt from those who had thought about suicide (suicide ideators) and control participan...

  20. Metabolic changes, hypothalamo-pituitary-adrenal axis and oxidative stress after short-term starvation in healthy pregnant women.

    Science.gov (United States)

    Schraag, Sabrina; Mandach, Ursula von; Schweer, Horst; Beinder, Ernst

    2007-01-01

    To compare metabolic effects and oxidative stress in pregnant and non-pregnant women after 12 h of fasting. Twenty-six healthy women with uncomplicated singleton pregnancies between the 24(th) and 28(th) gestational week were recruited. After an overnight fast, venous blood samples and urine samples were tested for metabolic parameters characteristic for starvation, cortisol and oxidative stress products. Healthy non-pregnant women matched by age, body mass index and length of fasting comprised the control group. The metabolic parameters beta-hydroxybutyrate and free fatty acids in blood and ketones in urine showed no differences in pregnant and non-pregnant women. However, the oxidative stress parameters, 8,12-iso-iPF(2alpha)-VI, isoprostanes and malondialdehyde were significantly higher in pregnant subjects, as was cortisol. Healthy pregnant women are exposed to oxidative stress and activation of the hypothalamo-pituitary-adrenal axis, but not to metabolic changes resembling starvation during short fasting periods in comparison to non-pregnant healthy women.

  1. Hair cortisol as a marker of hypothalamic-pituitary-adrenal Axis activity in female patients with major depressive disorder.

    Science.gov (United States)

    Pochigaeva, Ksenia; Druzhkova, Tatiana; Yakovlev, Alexander; Onufriev, Mikhail; Grishkina, Maria; Chepelev, Aleksey; Guekht, Alla; Gulyaeva, Natalia

    2017-04-01

    Hair cortisol is regarded as a promising marker of hypothalamic-pituitary-adrenal axis (HPAA) activity alterations due to stress, somatic and mental health conditions. Hair cortisol was previously reported to be elevated in patients with depression, however the data related to remission and recurrent depressive episodes are different. In this study, levels of hair cortisol were assessed in female patients with major depressive disorder (MDD) and the validity of hair cortisol as a marker of HPAA activity in this condition was evaluated. Hair cortisol was measured in 1 cm hair segments of 21 female patients with MDD and 22 female age-matched controls using enzyme-immunoassay analysis. Concurrently, serum cortisol was assessed and psychological status was evaluated using 17-item Hamilton Depression Rating Scale (HAMD-17), Beck Depression Inventory (BDI) and the Spielberger state trait anxiety inventory (STAI). The levels of hair cortisol were significantly lower in the MDD group, while serum cortisol levels were significantly higher in patients, as compared with controls. A significant negative correlation was found between HAMD-17 scores and hair cortisol. Decreased hair cortisol found in female patients with MDD as compared to controls suggests downregulation of HPAA activity during the preceding month. Further studies are needed to investigate the profiles of hair cortisol at different stages of depressive disorder to establish this parameter as a handy clinical tool.

  2. The effects of chronic SRIH-14 and octreotide administration on the pituitary-adrenal axis in adult male rats

    Directory of Open Access Journals (Sweden)

    S Trifunovic

    2009-08-01

    Full Text Available The effects of chronic treatments with SRIH-14 and octreotide on pituitary corticotropes (ACTH cells and on the adrenal cortex of male Wistar rats were examined. Adult males received two daily s.c. injections of 20 ?g/100 g of body weight of either SRIH-14 or octreotide for 28 consecutive days. ACTH cells were studied using a peroxidaseantiperoxidase immunocytochemical procedure. Morphometry was used to evaluate the changes in cell and nuclear volumes (?m3 and volume densities (% of ACTHimmunoreactive cells. The adrenal cortex was analyzed by histological and morphometric methods. A significant (p<0.05 decrease in body weight and in the absolute weights of the pituitary and adrenal glands was observed in both treated groups. Morphometric parameters of ACTH cells in both treated groups were not significantly (p>0.05 different than in control rats. The absolute volumes of the adrenal gland and adrenal cortex were significantly (p<0.05 decreased in both treated groups. The absolute and relative volumes of the zona glomerulosa (ZG, as well as the cellular and nuclear volumes of the ZG were significantly (p<0.05 decreased in the both treated groups. In rats treated with SRIH-14 and octreotide, the absolute and relative volumes of the zona fasciculata (ZF and zona reticularis (ZR, as well as their stereological parameters, did not change significantly (p>0.05. The aldosterone levels in the SRIH-14 and ocreotide-treated groups were significantly (p<0.05 decreased – by 13% and 19%, respectively. The concentration of ACTH and corticosterone did not change significantly. Together, these findings show that SRIH-14 and octreotide administration affected the morphological characteristics of the adrenal ZG in a similar manner, and brought about a decrease in plasma aldosterone concentration. These treatments did not affect pituitary ACTH cells or adrenal ZF and ZR functioning.

  3. Neurobiology of Maternal Stress: Role of Social Rank and Central Oxytocin in Hypothalamic-Pituitary Adrenal Axis Modulation

    Directory of Open Access Journals (Sweden)

    Jeremy D Coplan

    2015-07-01

    Full Text Available Background: Chronic stress may conceivably require plasticity of maternal physiology and behavior to cope with the conflicting primary demands of infant rearing and foraging for food. In addition, social rank may play a pivotal role in mandating divergent homeostatic adaptations in cohesive social groups. We examined cerebrospinal fluid (CSF oxytocin (OT levels and hypothalamic pituitary adrenal (HPA axis regulation in the context of maternal social stress and assessed the contribution of social rank to dyadic-distance as reflective of distraction from normative maternal-infant interaction. Methods: Twelve socially-housed mother-infant bonnet macaque dyads were studied after variable foraging demand (VFD exposure compared to 11 unstressed dyads. Dyadic-distance was determined by behavioral observation. Social ranking was performed blindly by two observers. Post-VFD maternal plasma cortisol and CSF OT were compared to corresponding measures in non-VFD exposed mothers. Results: High social rank was associated with increased dyadic-distance only in VFD-exposed dyads and not in control dyads. In mothers unexposed to VFD, social rank was not related to maternal cortisol levels whereas VFD-exposed dominant versus subordinate mothers exhibited increased plasma cortisol. Maternal CSF OT directly predicted maternal cortisol only in VFD-exposed mothers. CSF OT was higher in dominant versus subordinate mothers. VFD-exposed mothers with high cortisol specifically exhibited CSF OT elevations in comparison to control groups. Conclusions: Pairing of maternal social rank to dyadic-distance in VFD presumably reduces maternal contingent responsivity, with ensuing long-term sequelae. VFD-exposure dichotomizes maternal HPA axis response as a function of social rank with relatively reduced cortisol in subordinates. OT may serve as a homeostatic buffer during maternal stress exposure.

  4. Effects of early childhood trauma on hypothalamic-pituitary-adrenal (HPA) axis function in patients with Chronic Fatigue Syndrome.

    Science.gov (United States)

    Kempke, Stefan; Luyten, Patrick; De Coninck, Sarah; Van Houdenhove, Boudewijn; Mayes, Linda C; Claes, Stephan

    2015-02-01

    There is a paucity of studies that have investigated the assumption that early childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction in Chronic Fatigue Syndrome (CFS). The current study is the first to simultaneously investigate relationships among early childhood trauma, cortisol activity, and cortisol stress reactivity to psychosocial stress in a sample of well-screened CFS patients. We also examined whether self-critical perfectionism (SCP) plays a mediating role in the potential relationship between early trauma and neurobiological stress responses. A total of 40 female patients diagnosed with CFS were asked to provide morning saliva cortisol samples (after awakening, 30min later, and 1h later) for seven consecutive days as a measure of cortisol activity. In addition, patients were exposed to the Trier Social Stress Test, a well-validated stress test, to investigate the relationship between early childhood trauma and cortisol stress reactivity. Before the start of the study, patients completed the Childhood Trauma Questionnaire-Short form (CTQ-SF) as a measure of early childhood trauma (i.e. sexual, physical and emotional traumatic experiences). SCP was measured with the Depressive Experiences Questionnaire (DEQ). Data were analyzed by calculating several indices of cortisol secretion (i.e. Cortisol Awakening Response and Area Under the Curve). There was no association between early childhood trauma and cortisol as measured over the 7-day period. However, emotional neglect was significantly negatively related to cortisol reactivity in the TSST. SCP did not significantly mediate this association. Findings of this study suggest that emotional neglect is associated with blunted HPA axis reactivity, congruent with the assumption that CFS may reflect loss of adaptability of the neuroendocrine stress response system in at least a subgroup of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Disturbances in Hypothalamic-Pituitary-Adrenal Axis and Immunological Activity Differentiating between Unipolar and Bipolar Depressive Episodes.

    Directory of Open Access Journals (Sweden)

    Karlijn Becking

    Full Text Available Differentiating bipolar depression (BD from unipolar depression (UD is difficult in clinical practice and, consequently, accurate recognition of BD can take as long as nine years. Research has therefore focused on the discriminatory capacities of biomarkers, such as markers of the hypothalamic-pituitary-adrenal (HPA axis or immunological activity. However, no previous study included assessments of both systems, which is problematic as they may influence each other. Therefore, this study aimed to explore whether cortisol indicators and inflammatory markers were a independently associated with and/or b showed effect modification in relation to a lifetime (hypomanic episode in a large sample of depressed patients.Data were derived from the Netherlands Study of Depression and Anxiety and comprised 764 patients with a DSM-IV depressive disorder at baseline, of which 124 (16.2% had a lifetime (hypomanic episode at the 2-year assessment, or a more recent episode at the 4-year or 6-year assessment. Baseline cortisol awakening response, evening cortisol and diurnal cortisol slope were considered as cortisol indicators, while baseline C-reactive Protein (CRP, Interleukin-6 (IL-6, and Tumor Necrosis Factor Alpha (TNF-α were included as inflammatory markers.In depressed men and women, none of the cortisol indicators and inflammatory markers were (independently associated with a (hypomanic episode. However, effect modification was found of diurnal cortisol slope and CRP in relation to a (hypomanic episode. Further analyses showed that depressed men with high levels of diurnal cortisol slope and CRP had an increased odds (OR=10.99, p=.001 of having a (hypomanic episode. No significant differences were found in women.Our findings suggest that the combination of high diurnal cortisol slope and high CRP may differentiate between UD and BD. This stresses the importance of considering HPA-axis and immunological activity simultaneously, but more research is needed

  6. Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic-pituitary-adrenal axis activity.

    Science.gov (United States)

    Shivers, Kai-Yvonne; Amador, Nicole; Abrams, Lisa; Hunter, Deirtra; Jenab, Shirzad; Quiñones-Jenab, Vanya

    2015-04-01

    Although estrogen reduces inflammatory-mediated pain responses, the mechanisms behind its effects are unclear. This study investigated if estrogen modulates inflammatory signaling by reducing baseline or inflammation-induced cytokine levels in the injury-site, serum, dorsal root ganglia (DRG) and/or spinal cord. We further tested whether estrogen effects on cytokine levels are in part mediated through hypothalamic-pituitary-adrenal (HPA) axis activation. Lumbar DRG, spinal cord, serum, and hind paw tissue were analyzed for cytokine levels in 17β-estradiol-(20%) or vehicle-(100% cholesterol) treated female rats following ovariectomy/sham adrenalectomy (OVX), adrenalectomy/sham ovariectomy (ADX) or ADX+OVX operation at baseline and post formalin injection. Formalin significantly increased pro-inflammatory interleukin (IL)-6 levels in the paw, as well as pro- and anti-inflammatory cytokine levels in the DRG, spinal cord and serum in comparison to naïve conditions. Estrogen replacement significantly increased anti-inflammatory IL-10 levels in the DRG. Centrally, estradiol significantly decreased pro-inflammatory tumor necrosis factor (TNF)-α and IL-1β levels, as well as IL-10 levels, in the spinal cord in comparison to cholesterol treatment. At both sites, most estradiol modulatory effects occurred irrespective of pain or surgical condition. Estradiol alone had no influence on cytokine release in the paw or serum, indicating that estrogen effects were site-specific. Although cytokine levels were altered between surgical conditions at baseline and following formalin administration, ADX operation did not significantly reverse estradiol's modulation of cytokine levels. These results suggest that estrogen directly regulates cytokines independent of HPA axis activity in vivo, in part by reducing cytokine levels in the spinal cord.

  7. Relationship between glutamate in the limbic system and hypothalamus-pituitary-adrenal axis after middle cerebral artery occlusion in rats

    Institute of Scientific and Technical Information of China (English)

    何明利; 陈漫娥; 王景周; 郭光华; 郑衍平; 蒋晓江; 张猛

    2003-01-01

    Objective To investigate the features of glutamate activity in the limbic system and the effects of glutamate on the activation of the hypothalamus-pituitary-adrenal (HPA) axis throughout both acute cerebral ischemia and reperfusion.Methods The changes in glutamate content in the nervous cell gap, in corticotrophin releasing hormone (CHR) mRNA expression level in brain tissue, and in adrenocorticotropic hormone in blood plasma at different time-points after middle cerebral artery occlusion (MCAO) in rats were determined respectively with high-performance liquid chomatography (HPLC) and in situ hybridization.Results Glutamate content in the hippocampus and the hypothalamus increased rapidly at ischemia 15 minutes, and reached peak value (the averages were 21.05 mg/g±2.88 mg/g and 14.20 mg/g±2.58 mg/g, respectively) at 1 hour after middle cerebral artery occlusion. During recirculation, it returned rapidly to the baseline level. At 24 hours after reperfusion, it went up once more, and remained at a relative high level until 48 hours after reperfusion, and then declined gradually. CRH mRNA expression levels in the temporal cortex, hippocampus and hypothalamus were enhanced markedly at 1 hour ischemia and were maintained until 96 hours after reperfusion. At the same time, adrenocorticotropic hormone level in plasma was relatively increased. In the peak stage of reperfusion injury, there was a significantly positive correlation (n=15, r=0.566, P<0.05) of the glutamate contents in the hypothalamus with the number of cells positive for CRH mRNA expression level in the hypothalamus.Conclusion It is probable that the CRH system in the central nervous system is mainly distributed in the limbic system, and glutamate might be one of the trigger factors to induce excessive stress response in the HPA axis.

  8. Impact of maternal undernutrition during the periconceptional period, fetal number, and fetal sex on the development of the hypothalamo-pituitary adrenal axis in sheep during late gestation.

    Science.gov (United States)

    Edwards, L J; McMillen, I Caroline

    2002-05-01

    Evidence from epidemiologic, clinical, and experimental studies has shown that a suboptimal intrauterine environment during early pregnancy can alter fetal growth and gestation length and is associated with an increased prevalence of adult hypertension and cardiovascular disease. It has been postulated that maternal nutrient restriction may act to reprogram the development of the pituitary-adrenal axis, resulting in excess glucocorticoid exposure and adverse health outcomes in later life. It is unknown, however, whether maternal nutrient restriction during the periconceptional period alters the development of the fetal pituitary-adrenal axis or whether the effects of periconceptional undernutrition can be reversed by the provision of an adequate level of maternal nutrition throughout the remainder of pregnancy. We have investigated the effect of restricted periconceptional nutrition (70% of control feed allowance) from 60 days before until 7 days after mating and the effect of restricted gestational nutrition from Day 8 to 147 of gestation on the development of the fetal hypothalamo-pituitary adrenal (HPA) axis in the sheep. In these studies, we have also investigated the effects of fetal number and sex on the pituitary-adrenal responses to periconceptional and gestational undernutrition. In ewes maintained on a control diet throughout the periconceptional and gestational periods, fetal plasma ACTH concentrations were higher and the prepartum surge in cortisol occurred earlier in singletons compared with twins. Plasma ACTH concentrations were also significantly higher in male compared with female singletons, and in twin fetuses, the prepartum surge in cortisol concentrations occurred earlier in males than in females. Periconceptional undernutrition resulted in higher fetal plasma concentrations of ACTH between 110 and 145 days of gestation and a significantly greater cortisol response to a bolus dose of corticotropin-releasing hormone in twin, but not singleton

  9. Associations between anthropometrical measurements, body composition, single-nucleotide polymorphisms of the hypothalamus/pituitary/adrenal (HPA) axis and HPA axis functioning.

    Science.gov (United States)

    Rutters, Femke; Nieuwenhuizen, Arie G; Lemmens, Sofie G T; Bouwman, Freek; Mariman, Edwin; Westerterp-Plantenga, Margriet S

    2011-06-01

    The relationship between hypothalamus/pituitary/adrenal (HPA) axis functioning and (visceral) obesity may be explained by single-nucleotide polymorphisms (SNPs) of the HPA axis. Objective  To investigate the relationship between the HPA axis SNP's 'BclI' in the glucocorticoid receptor gene and C8246T in the POMC gene and anthropometric measurements, body composition, 5-h cortisol concentrations, HPA axis feedback sensitivity, as well as HPA axis feedback sensitivity under stress in men and women. DESIGN/SUBJECTS/MEASUREMENTS: We assessed in 92 men and 102 women (18-55 years, BMI 19-41 kg/m(2) ) anthropometry, body composition using hydrodensitometry and deuterium dilution method, cortisol variability by measuring 5-h cortisol concentrations, HPA axis feedback functioning using a dexamethasone suppression test and HPA axis functioning under a challenged condition consisting of a standardized high intensity test with ingestion of 4 mg dexamethasone. In female participants, the 8246C allele carriers compared to the 8246T allele carries were associated with a higher 5-h cortisol exposure (1·52 × 10(5) ± 0·8 vs 1·18 × 10(5) ± 0·6 nm·min, P < 0·05) and higher baseline postdexamethasone cortisol concentrations (54·5 ± 35·6 vs 37·4 ± 18·5 nm, P < 0·05). In male participants regarding the C8246T allele carriers and in both male and female participants regarding the BclI genotypes, no significant differences in anthropometric measurements, body composition and HPA axis functioning were observed. Multiple regression analysis showed that only increased 5-h cortisol exposure significantly related to changes in anthropometric measurements and body composition; the BclI and C8246T genotypes were not associated. Our preliminary data show that in both men and women (18-55 years, BMI 19-41 kg/m(2) ), the SNP's BclI and C8246T of the HPA axis were primarily related to altered HPA axis functioning, rather than to altered anthropometric measurements and body

  10. Volume of the adrenal and pituitary glands in depression

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Willer, Inge Stoel; Knorr, Ulla

    2011-01-01

    Numerous studies have shown that the hypothalamic-pituitary-adrenal (HPA) axis is hyperactive in some depressed patients. It is unclear whether such hyperactivity results in changed volumes of the adrenal glands, pituitary gland and hypothalamus. We systematically reviewed all controlled studies ...

  11. Sex-specific prediction of hypothalamic-pituitary-adrenal axis activity by pituitary volume during adolescence: a longitudinal study from 12 to 17 years of age.

    Science.gov (United States)

    Kaess, Michael; Simmons, Julian G; Whittle, Sarah; Jovev, Martina; Chanen, Andrew M; Yücel, Murat; Pantelis, Christos; Allen, Nicholas B

    2013-11-01

    To investigate the longitudinal relationship between pituitary gland volume (PGV) and parameters of hypothalamic-pituitary-adrenal axis (HPAA) functioning during adolescence. Participants were 49 adolescents (19 girls and 30 boys) selected from a larger longitudinal, population-based study of adolescent development. Assessments were conducted at three time points (S1, S2 and S3). MRI sessions were at S1 (age: M=12.62, SD=0.45 years) and S3 (M=16.48, SD=0.53 years) and multiple assessments of salivary cortisol were undertaken at S2 (M=15.51, SD=0.35 years). PGV was measured via previously validated manual tracing methods, and the cortisol awakening response (CAR) and diurnal slope (DSL) were used as indices of HPAA functioning. A significant sex-linked interaction was found for PGV at S1 predicting both CAR (p=0.025) and DSL (p=0.009) at S2. Specifically, PGV at S1 significantly predicted CAR (p=0.033) and DSL (p=0.010) in boys only, with no significant results found for girls. Neither CAR nor DSL at S2 predicted growth of PGV from S1 to S3. PGV in early adolescence predicted HPAA functioning in mid-adolescent boys but not in girls. The results suggest a significant influence of sex-specific development on the relationship between PGV and HPAA activity and reactivity. The findings have potential implications for understanding and interpreting sex-linked and stress related clinical disorders that emerge during mid-to-late adolescence. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Brain Mast Cells Act as an Immune Gate to the Hypothalamic-Pituitary-Adrenal Axis in Dogs

    OpenAIRE

    Matsumoto, Itsuro; Inoue, Yasuhisa; Shimada, Toshio; Aikawa, Tadaomi

    2001-01-01

    Mast cells perform a significant role in the host defense against parasitic and some bacterial infections. Here we show that in the dog, degranulation of brain mast cells evokes hypothalamic-pituitary-adrenal responses via histamine release. A large number of mast cells were found in a circumscribed ventral region of the hypothalamus, including the pars tuberalis and median eminence. When these intracranial mast cells were passively sensitized with immunoglobulin E via either the intracerebro...

  13. Hypothalamic-pituitary-adrenal axis tonus is associated with hippocampal microstructural asymmetry

    DEFF Research Database (Denmark)

    Madsen, Kathrine Skak; Jernigan, Terry L; Iversen, Pernille

    2012-01-01

    It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since there is gr...

  14. Breast-Milk Cortisol and Cortisone Concentrations Follow the Diurnal Rhythm of Maternal Hypothalamus-Pituitary-Adrenal Axis Activity.

    Science.gov (United States)

    van der Voorn, Bibian; de Waard, Marita; van Goudoever, Johannes B; Rotteveel, Joost; Heijboer, Annemieke C; Finken, Martijn Jj

    2016-11-01

    Very preterm infants often receive donor milk from mothers who deliver at term, but its composition differs from that of their own mother's milk. Because breast-milk glucocorticoids can support developing neonates, we explored concentration variability within and between mothers. We hypothesized that breast-milk glucocorticoid concentrations would be higher after very preterm delivery [gestational age (GA) cortisone, and the cortisone-to-(cortisol+cortisone) ratio of mothers who delivered at (median) GA: 28.6 wk or at term weekly during the first month postpartum. Study 2 assessed variations in milk cortisol, cortisone, and the cortisone-to-(cortisol+cortisone) ratio over 24 h, and tested Pearson correlations between milk and salivary concentrations in mothers who delivered at term (median GA: 38.9 wk) during week 4 postpartum. In these studies, foremilk glucocorticoids were measured by liquid chromatography-tandem mass spectrometry. Associations of milk cortisol, milk cortisone, and the milk cortisone-to-(cortisol+cortisone) ratio with prematurity (study 1) or collection time (study 2) were studied with longitudinal data analyses. In study 1, giving birth to a very preterm infant was associated with reductions in milk cortisol and cortisone concentrations of 50% (β: 0.50; 95% CI: 0.26, 0.99; P = 0.05) and 53% (β: 0.53; 95% CI: 0.30, 0.93; P = 0.03), respectively, when adjusted for collection time. In study 2, concentrations of milk cortisol and cortisone were associated with collection time (both P cortisone (r = 0.93, P cortisone-to-(cortisol+cortisone) ratio (r = 0.64, P < 0.01) were correlated with one another. Breast-milk glucocorticoid concentrations follow the diurnal rhythm of maternal hypothalamus-pituitary-adrenal axis activity and are lower in mothers who deliver very preterm. © 2016 American Society for Nutrition.

  15. [The relationship of ultrastructure and function of hypothalamus-pituitary-adrenal axis in early stage of sepsis in rats].

    Science.gov (United States)

    Zhang, Yu-xiang; Li, Hong-shan; Ma, Peng-lin

    2011-05-01

    To observe the changes in ultrastructure and function of hypothalamic-pituitary-adrenal axis (HPAA), and to approach the relationship between them in early stage of sepsis in rats. Thirty male Sprague-Dawley (SD) rats were randomly divided into normal control group, sham group, sepsis group. The sepsis model was reproduced by cecal ligation and puncture (CLP). The rats were sacrificed after collection of blood at 6 hours after CLP, and the levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in the plasma, and the corticotropin release hormone (CRH) in the tissue of hypothalamus were detected. The histopathological changes in HPAA were observed with transmission electron microscopy. The levels of ACTH and CORT in plasma, and the CRH in hypothalamus tissue of sepsis group were increased in the early stage of sepsis compared with the normal control group or sham group [ACTH (pmol/L): 5.78±0.36 vs. 1.94±0.31, 2.51±0.10; CORT (nmol/L): 88.48±4.47 vs. 22.02±1.62, 34.20±2.51; CRH (μg/L): 101.92±6.61 vs. 61.65±6.05, 66.65±4.03, PHPAA was excessively activated, and ACTH and CORT in plasma, and CRH in hypothalamus were significantly increased in early stage of sepsis. The changes in ultrastructure of HPAA were obvious, and the change in function was closely related to the ultrastructural changes.

  16. Decreased maternal hypothalamic-pituitary-adrenal axis activity in very severely obese pregnancy: Associations with birthweight and gestation at delivery.

    Science.gov (United States)

    Stirrat, Laura I; O'Reilly, James R; Barr, Sarah M; Andrew, Ruth; Riley, Simon C; Howie, Alexander F; Bowman, Maria; Smith, Roger; Lewis, John G; Denison, Fiona C; Forbes, Shareen; Seckl, Jonathan R; Walker, Brian R; Norman, Jane E; Reynolds, Rebecca M

    2016-01-01

    The maternal hypothalamic-pituitary-adrenal-axis (HPAA) undergoes dramatic activation during pregnancy. Increased cortisol and corticotrophin-releasing-hormone (CRH) associate with low birthweight and preterm labor. In non-pregnant obesity, the HPAA is activated but circulating cortisol levels are normal or lower than in lean women. We hypothesized that maternal cortisol levels would be lower in obese pregnancy, and would associate with increased fetal size and length of gestation. Fasting serum cortisol was measured at 16, 28 and 36 weeks gestation and at 3-6 months postpartum in 276 severely obese and 135 lean women. In a subset of obese (n=20) and lean (n=20) we measured CRH, hormones that regulate bioavailable cortisol (corticosteroid-binding-globulin, estradiol, estriol, and progesterone). Urinary glucocorticoid metabolites were measured in pregnant (obese n=6, lean n=5) and non-pregnant (obese n=7, lean n=7) subjects. Maternal cortisol and HPAA hormones were lower in obese pregnancy. Total urinary glucocorticoid metabolites increased significantly in lean pregnancy, but not in obese. Lower maternal cortisol in obese tended to be associated with increased birthweight (r=-0.13, p=0.066). In obese, CRH at 28 weeks correlated inversely with gestational length (r=-0.49, p=0.04), and independently predicted gestational length after adjustment for confounding factors (mean decrease in CRH of -0.25 pmol/L (95% CI -0.45 to -0.043 pmol/L) per/day increase in gestation). In obese pregnancy, lower maternal cortisol without an increase in urinary glucocorticoid clearance may indicate a lesser activation of the HPAA than in lean pregnancy. This may offer a novel mechanism underlying increased birthweight and longer gestation in obese pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Interleukin-6 is an afferent signal to the hypothalamo-pituitary-adrenal axis during local inflammation in mice.

    Science.gov (United States)

    Turnbull, Andrew V; Prehar, Sukhpal; Kennedy, Adam R; Little, Roderick A; Hopkins, Stephen J

    2003-05-01

    The cytokines IL-1 and IL-6 are able to induce prostaglandin (PG)-dependent activation of the hypothalamo-pituitary-adrenal axis (HPAA) and are thought to play key roles in immune-neuroendocrine interactions during inflammation. The present study shows that inflammation induced by im injection of turpentine (TPS) in the hind limb of mice causes an increase in the plasma concentration of IL-6, but not that of IL-1 alpha or IL-1 beta, together with a prolonged (>18-h) activation of the HPAA. IL-6 plays a causal role in the TPS-induced elevation in HPAA activity, because the sustained (8-18 h) increases in 1) plasma corticosterone, 2) plasma ACTH, and 3) induction of c-Fos in the hypothalamic paraventricular nucleus are all markedly blunted in IL-6-deficient (IL-6(-/-)) mice. Peripheral administration of a neutralizing IL-6 antiserum inhibited the plasma corticosterone response of normal (C57BL/6) mice to hind limb inflammation to an extent similar to that seen in IL-6(-/-) mice, suggesting that the IL-6 responsible for the increased HPAA activity is produced, or acts, on the blood side of the blood-brain barrier. We also show that IL-6 in the circulation is induced almost exclusively at the local inflammatory site, where IL-1 beta is produced. Induction of IL-6 and activation of the HPAA are dependent upon prior activation of an IL-1 type I receptor, as both are inhibited in type I IL-1 receptor-deficient mice. Furthermore, hind limb inflammation induced cyclooxygenase-2 protein expression around the cerebrovasculature of normal (IL-6(+/+)), but not IL-6(-/-), mice. Based on these data, we propose that IL-6 is produced at the local inflammatory site under the control of IL-1 beta and is the circulating afferent signal that is in part responsible for elevated HPAA activity, possibly acting via eicosanoid production within the cerebrovasculature.

  18. Hypothalamic-Pituitary-Adrenal Axis Function in Dissociative Disorders, PTSD, and Healthy Volunteers

    Science.gov (United States)

    Simeon, Daphne; Knutelska, Margaret; Yehuda, Rachel; Putnam, Frank; Schmeidler, James; Smith, Lisa M.

    2007-01-01

    Background This study investigated basal and stress-induced HPA axis alterations in dissociative disorders (DD). Methods Forty-six subjects with DD without lifetime PTSD, 35 subjects with PTSD, and 58 HC subjects, free of current major depression, were studied as inpatients. After a 24-hour urine collection and hourly blood sampling for ambient cortisol determination, a low-dose dexamethasone suppression test was administered, followed by the Trier Social Stress Test. Results The DD group had significantly elevated urinary cortisol compared to the HC group, more pronounced in the absence of lifetime major depression, whereas the PTSD and HC groups did not differ. The DD group demonstrated significantly greater resistance to, and faster escape from, dexamethasone suppression compared to the HC group, whereas the PTSD and HC groups did not differ. The three groups did not differ in cortisol stress reactivity, but both psychiatric groups demonstrated a significant inverse correlation between dissociation severity and cortisol reactivity, after controlling for all other symptomatology. The PTSD subgroup with comorbid DD tended to have blunted reactivity compared to the HC group. Conclusions The study demonstrates a distinct pattern of HPA axis dysregulation in DD, emphasizing the importance of further study of stress response systems in dissociative psychopathology. PMID:17137559

  19. Sound conditioning protects hearing by activating the hypothalamic-pituitary-adrenal axis.

    Science.gov (United States)

    Tahera, Yeasmin; Meltser, Inna; Johansson, Peter; Salman, Hazim; Canlon, Barbara

    2007-01-01

    Sound conditioning primes the auditory system to low levels of acoustic stimuli and reduces damage caused by a subsequent acoustic trauma. This priming activates the HPA axis resulting in the elevation of plasma corticosterone with a consequent upregulation of glucocorticoid receptors (GR) in the cochlea and the paraventricular nucleus (PVN) of the hypothalamus in the mouse. This protective effect is blocked by adrenalectomy or pharmacological treatment with RU486 + metyrapone. Sound conditioning prevents GR down-regulation induced by acoustic trauma and subsequently enhances GR activity in spiral ganglion neurons. Increased SRC-1 expression, triggered by sound conditioning, positively correlates with the upregulation of GR in the cochlea. These findings will help to define the cellular mechanisms responsible for protecting the auditory system from hearing loss by sound conditioning.

  20. FGF1 and FGF19 reverse diabetes by suppression of the hypothalamic-pituitary-adrenal axis.

    Science.gov (United States)

    Perry, Rachel J; Lee, Sangwon; Ma, Lie; Zhang, Dongyan; Schlessinger, Joseph; Shulman, Gerald I

    2015-04-28

    Fibroblast growth factor-1 (FGF1) and FGF19 have been shown to improve glucose metabolism in diabetic rodents, but how this occurs is unknown. Here to investigate the mechanism of action of these growth factors, we perform intracerebroventricular (i.c.v.) injections of recombinant FGF1 or FGF19 in an awake rat model of type 1 diabetes (T1D) and measure rates of whole-body lipolysis, hepatic acetyl CoA content, pyruvate carboxylase activity and hepatic glucose production. We show that i.c.v. injection of FGF19 or FGF1 leads to a ∼60% reduction in hepatic glucose production, hepatic acetyl CoA content and whole-body lipolysis, which results from decreases in plasma ACTH and corticosterone concentrations. These effects are abrogated by an intra-arterial infusion of corticosterone. Taken together these studies identify suppression of the HPA axis and ensuing reductions in hepatic acetyl CoA content as a common mechanism responsible for mediating the acute, insulin-independent, glucose-lowering effects of FGF1 and FGF19 in rodents with poorly controlled T1D.

  1. Examining the role of endogenous orexins in hypothalamus-pituitary-adrenal axis endocrine function using transient dual orexin receptor antagonism in the rat.

    Science.gov (United States)

    Steiner, Michel A; Sciarretta, Carla; Brisbare-Roch, Catherine; Strasser, Daniel S; Studer, Rolf; Jenck, Francois

    2013-04-01

    The orexin neuropeptide system regulates wakefulness and contributes to physiological and behavioral stress responses. Moreover, a role for orexins in modulating hypothalamus-pituitary-adrenal (HPA) axis activity has been proposed. Brain penetrating dual orexin receptor (OXR) antagonists such as almorexant decrease vigilance and have emerged as a novel therapeutic class for the treatment of insomnia. Almorexant was used here as a pharmacological tool to examine the role of endogenous orexin signaling in HPA axis endocrine function under natural conditions. After confirming the expression of prepro-orexin and OXR-1 and OXR-2 mRNA in hypothalamus, pituitary and adrenal glands, the effects of systemic almorexant were investigated on peripheral HPA axis hormone release in the rat under baseline, stress and pharmacological challenge conditions. Almorexant did not alter basal or stress-induced corticosterone release despite affecting wake and sleep stages (detected by radiotelemetric electroencephalography/electromyography) during the stress exposure. Moreover, almorexant did not affect the release of adrenocorticotropin (ACTH) and corticosterone at different time points along the diurnal rhythm, nor corticotrophin-releasing hormone (CRH)- and ACTH-stimulated neuroendocrine responses, measured in vivo under stress-free conditions. These results illustrate that dual OXR antagonists, despite modulating stress-induced wakefulness, do not interfere with endocrine HPA axis function in the rat. They converge to suggest that endogenous orexin signaling plays a minor role in stress hormone release under basal conditions and under challenge.

  2. Short-term safety assessment of clobetasol propionate 0.05% shampoo: hypothalamic-pituitary-adrenal axis suppression, atrophogenicity, and ocular safety in subjects with scalp psoriasis.

    Science.gov (United States)

    Andres, Philippe; Poncet, Michel; Farzaneh, Sidou; Soto, Pascale

    2006-04-01

    Clobetasol propionate is known to be a very effective treatment for psoriasis; however, its use is limited by potent corticosteroid class related side effects such as hypothalamic-pituitary-adrenal (HPA) axis suppression and atrophogenicity. The aim of this single-center, parallel group, randomized study was to assess the HPA axis suppression potential, atrophogenicity, and ocular tolerability of clobetasol propionate shampoo in 26 patients with scalp psoriasis. Suitable subjects were treated once daily for 4 weeks with clobetasol propionate shampoo, to be rinsed off after 15 minutes or with a leave-on clobetasol propionate gel. The study demonstrated that clobetasol propionate shampoo did not lead to HPA axis suppression or to skin atrophy. Conversely, the gel led to HPA axis suppression and a decrease in skin thickness. Neither formulation had an impact on ocular safety. Despite the short contact application time, the clobetasol propionate shampoo provides similar efficacy results to the gel.

  3. Recovery of the hypothalamic-pituitary-adrenal axis in children and adolescents after surgical cure of Cushing's disease.

    Science.gov (United States)

    Lodish, Maya; Dunn, Somya Verma; Sinaii, Ninet; Keil, Margaret F; Stratakis, Constantine A

    2012-05-01

    Recovery of the hypothalamic-pituitary-adrenal axis (HPAA) after transsphenoidal surgery (TSS) for Cushing's disease (CD) in children has not been adequately studied. Our objective was to assess time to recovery of the HPAA after TSS in children with CD. This was a case series at the National Institutes of Health Clinical Center. Fifty-seven patients with CD (6-18 yr, mean 13.0 ± 3.1 yr) given a standard regimen of glucocorticoid tapering after TSS were studied out of a total of 73 recruited. ACTH (250 μg) stimulation tests were administered at approximately 6-month intervals for up to 36 months. Age, sex, pubertal status, body mass index, length of disease, midnight cortisol, and urinary free cortisol at diagnosis were analyzed for effects on recovery. The main outcome measure was complete recovery of the HPAA as defined by a cortisol level of at least 18 μg/dl in response to 250 μg ACTH. Full recovery was reached by 43 (75.4%) of 57 patients, with 29 of the 43 (67.4%) and 41 of the 43 (95.3%) recovering by 12 and 18 months, respectively. The overall mean time to recovery was 12.6 ± 3.3 months. Kaplan-Meier survivor function estimated a 50% chance of recovering by 12 months after TSS and 75% chance of recovering within 14 months. By receiver operating characteristic curve assessment, the cutoff of at least 10-11 μg/dl of cortisol as the peak of ACTH stimulation testing at 6 months after TSS yielded the highest sensitivity (70-80%) and specificity (64-73%) to predict full recovery of the HPAA at 12 months. Two of the four patients that recovered fully within 6 months had recurrent CD. Although this is not a randomized study, we present our standardized tapering regimen for glucocorticoid replacement after TSS that led to recovery of the HPAA in most patients within the first postoperative year. Multiple factors may affect this process, but an early recovery may indicate disease recurrence.

  4. Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

    Science.gov (United States)

    Annabi, Alya; Dhouib, Ines Bini; Lamine, Aicha Jrad; El Golli, Nargès; Gharbi, Najoua; El Fazâa, Saloua; Lasram, Mohamed Montassar

    2015-01-01

    Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

  5. Hormonal status modifies renin-angiotensin system-regulating aminopeptidases and vasopressin-degrading activity in the hypothalamus-pituitary-adrenal axis of female mice.

    Science.gov (United States)

    García, María Jesús; Martínez-Martos, José Manuel; Mayas, María Dolores; Carrera, María Pilar; De la Chica, Susana; Cortés, Pedro; Ramírez-Expósito, María Jesús

    2008-07-01

    The hypothalamus-pituitary-adrenal axis (HPA) participates in the maintenance of cardiovascular functions and in the control of blood pressure. By other hand, it is known that blood pressure regulation and HPA activity are affected by sex hormones. The aim of the present work is to analyze the influence of estradiol and progesterone on renin-angiotensin system (RAS)-regulating aminopeptidase A, aminopeptidase B and aminopeptidase N activities and vasopressin-degrading activity in the HPA axis of ovariectomized mice and ovariectomized mice treated subscutaneously with different doses of estradiol and progesterone. Our data suggest that in female mice, estradiol and progesterone influence RAS-regulating and vasopressin-degrading activities at different levels of the HPA axis.

  6. Polymorphisms of genes related to the hypothalamic-pituitary-adrenal axis influence the cortisol awakening response as well as self-perceived stress.

    Science.gov (United States)

    Li-Tempel, Ting; Larra, Mauro F; Winnikes, Ulrike; Tempel, Tobias; DeRijk, Roel H; Schulz, André; Schächinger, Hartmut; Meyer, Jobst; Schote, Andrea B

    2016-09-01

    The hypothalamus-pituitary-adrenal (HPA) axis is a crucial endocrine system for coping with stress. A reliable and stable marker for the basal state of that system is the cortisol awakening response (CAR). We examined the influence of variants of four relevant candidate genes; the mineralocorticoid receptor gene (MR), the glucocorticoid receptor gene (GR), the serotonin transporter gene (5-HTT) and the gene encoding the brain-derived neurotrophic factor (BDNF) on CAR and self-perceived stress in 217 healthy subjects. We found that polymorphisms of GR influenced both, the basal state of the HPA axis as well as self-perceived stress. MR only associated with self-perceived stress and 5-HTT only with CAR. BDNF did not affected any of the investigated indices. In summary, we suggest that GR variants together with the CAR and supplemented with self reports on perceived stress might be useful indicators for the basal HPA axis activity.

  7. Acupuncture Relieves the Excessive Excitation of Hypothalamic-Pituitary-Adrenal Cortex Axis Function and Correlates with the Regulatory Mechanism of GR, CRH, and ACTHR

    Directory of Open Access Journals (Sweden)

    Shao-Jun Wang

    2014-01-01

    Full Text Available It had been indicated in the previous studies that acupuncture relieved the excessive excitation of hypothalamic-pituitary-adrenal cortex axis (HPAA function induced by stress stimulation. But the changes in glucocorticoid receptor (GR induced by acupuncture have not been detected clearly. The objective of the study was to observe the impacts of acupuncture on the protein expressions of corticotrophin releasing hormone (CRH, adrenocorticotropic hormone receptor (ACTHR, and GR under the physiological and stress states. The results showed that under the stress state, acupuncture upregulated the protein expression of GR in the hippocampus, hypothalamic paraventricular nucleus (PVN, and pituitary gland, downregulated the protein expression of GR in the adrenal cortex, and obviously reduced the protein expressions of CRH and ACTHR. Under the physiological state, acupuncture promoted GR protein expression in the hippocampus and CRH protein expression in the hippocampus and PVN. The results explained that acupuncture regulated the stress reaction via promoting the combination of glucocorticoids (GC with GR, and GR protein expression. The increase of GR protein expression induced feedback inhibition on the overexpression of CRH and ACTHR, likely decreased GC level, and caused the reduction of GR protein expression in the adrenal cortex.

  8. Acupuncture Relieves the Excessive Excitation of Hypothalamic-Pituitary-Adrenal Cortex Axis Function and Correlates with the Regulatory Mechanism of GR, CRH, and ACTHR

    Science.gov (United States)

    Wang, Shao-Jun; Zhang, Jiao-Jiao; Qie, Li-Li

    2014-01-01

    It had been indicated in the previous studies that acupuncture relieved the excessive excitation of hypothalamic-pituitary-adrenal cortex axis (HPAA) function induced by stress stimulation. But the changes in glucocorticoid receptor (GR) induced by acupuncture have not been detected clearly. The objective of the study was to observe the impacts of acupuncture on the protein expressions of corticotrophin releasing hormone (CRH), adrenocorticotropic hormone receptor (ACTHR), and GR under the physiological and stress states. The results showed that under the stress state, acupuncture upregulated the protein expression of GR in the hippocampus, hypothalamic paraventricular nucleus (PVN), and pituitary gland, downregulated the protein expression of GR in the adrenal cortex, and obviously reduced the protein expressions of CRH and ACTHR. Under the physiological state, acupuncture promoted GR protein expression in the hippocampus and CRH protein expression in the hippocampus and PVN. The results explained that acupuncture regulated the stress reaction via promoting the combination of glucocorticoids (GC) with GR, and GR protein expression. The increase of GR protein expression induced feedback inhibition on the overexpression of CRH and ACTHR, likely decreased GC level, and caused the reduction of GR protein expression in the adrenal cortex. PMID:24761151

  9. Acupuncture Relieves the Excessive Excitation of Hypothalamic-Pituitary-Adrenal Cortex Axis Function and Correlates with the Regulatory Mechanism of GR, CRH, and ACTHR.

    Science.gov (United States)

    Wang, Shao-Jun; Zhang, Jiao-Jiao; Qie, Li-Li

    2014-01-01

    It had been indicated in the previous studies that acupuncture relieved the excessive excitation of hypothalamic-pituitary-adrenal cortex axis (HPAA) function induced by stress stimulation. But the changes in glucocorticoid receptor (GR) induced by acupuncture have not been detected clearly. The objective of the study was to observe the impacts of acupuncture on the protein expressions of corticotrophin releasing hormone (CRH), adrenocorticotropic hormone receptor (ACTHR), and GR under the physiological and stress states. The results showed that under the stress state, acupuncture upregulated the protein expression of GR in the hippocampus, hypothalamic paraventricular nucleus (PVN), and pituitary gland, downregulated the protein expression of GR in the adrenal cortex, and obviously reduced the protein expressions of CRH and ACTHR. Under the physiological state, acupuncture promoted GR protein expression in the hippocampus and CRH protein expression in the hippocampus and PVN. The results explained that acupuncture regulated the stress reaction via promoting the combination of glucocorticoids (GC) with GR, and GR protein expression. The increase of GR protein expression induced feedback inhibition on the overexpression of CRH and ACTHR, likely decreased GC level, and caused the reduction of GR protein expression in the adrenal cortex.

  10. 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.

  11. Volume of the adrenal and pituitary glands in depression

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Willer, Inge Stoel; Knorr, Ulla

    2011-01-01

    Numerous studies have shown that the hypothalamic-pituitary-adrenal (HPA) axis is hyperactive in some depressed patients. It is unclear whether such hyperactivity results in changed volumes of the adrenal glands, pituitary gland and hypothalamus. We systematically reviewed all controlled studies...... on the adrenal or pituitary glands or hypothalamus volume in unipolar depressive disorder published in PubMed 1966 to December 2009. We identified three studies that investigated the volume of the adrenal glands and eight studies that examined the volume of the pituitary gland, but no studies on hypothalamus...... identified such as small population samples, different subtypes of depression and insufficient matching of patients and controls. Due to large heterogeneity of study designs and data, it was futile to make a meta-analysis. It is concluded that it remains unclear whether hyperactivity of the HPA axis results...

  12. The effect of hypothalamo-pituitary disconnection on the functional and morphologic development of the pituitary-adrenal axis in the fetal sheep in the last third of gestation.

    Science.gov (United States)

    Antolovich, G C; McMillen, I C; Robinson, P M; Silver, M; Young, I R; Perry, R A

    1991-09-01

    We have investigated the effect of hypothalamo-pituitary disconnection (HPD) on the maturation of basal ir-ACTH and cortisol concentrations in fetal sheep plasma, and on the development of the anterior pituitary corticotroph population in the last third of gestation. After HPD, fetal plasma ir-ACTH concentrations were significantly elevated, and continued to rise with increasing gestational age. However, despite elevated ir-ACTH concentrations, there was no increase in fetal plasma cortisol concentrations, and parturition was delayed for at least 8 days beyond normal term. Furthermore, HPD resulted in a significant disruption of the maturation of the pars distalis corticotrophs. We also examined the change in fetal plasma concentrations of ir-ACTH and cortisol to exogenous CRF after HPD. There was a significant increase in plasma ir-ACTH in response to CRF administration in the HPD fetuses, which was qualitatively similar to that observed in sham-operated fetuses. In contrast, the plasma cortisol response was less in HPD fetuses when compared to that in sham-operated fetuses. The results of this study demonstrate that ir-ACTH secretion is not maintained by the fetal hypothalamus in the last third of gestation, and that ir-ACTH secretion is tonically inhibited by the hypothalamus during this time. The disconnection of the pituitary from the hypothalamus disrupts the maturation of the pituitary-adrenal axis, thus demonstrating the fundamental importance of the hypothalamo-pituitary axis in the normal maturational cascade which culminates in birth in this species.

  13. Multigenerational effects of fetal dexamethasone exposure on the hypothalamic-pituitary-adrenal axis of first- and second-generation female offspring.

    Science.gov (United States)

    Long, Nathan M; Ford, Stephen P; Nathanielsz, Peter W

    2013-03-01

    Synthetic glucocorticoid (sGC) administration to women threatening preterm delivery increases neonatal survival. Evidence shows that fetal exposure to glucocorticoid levels higher than appropriate for current maturation programs offspring development. We examined fetal sGC multigenerational effects on F1 and F2 female offspring hypothalamo-pituitary-adrenal axis (HPAA) function. At 0.7 gestation, pregnant F0 ewes received 4 dexamethasone injections (2 mg, approximately 60 μg/kg(-1) per day(-1), 12 hours apart) or saline (control). F1 female offspring were bred to produce F2 female offspring. Postpubertal HPAA function was tested in F1 and F2 ewes. F1 and F2 ewe lambs showed reduced birthweight and morphometrics. Dexamethasone increased baseline but reduced stimulated HPAA activity in F1 and F2 female offspring. This is the first demonstration that sGC doses in the clinical range have multigenerational effects on hypothalamo-pituitary-adrenal activity in a precocial species, indicating the need for the study of long-term effects of fetal sGC exposure. Copyright © 2013 Mosby, Inc. All rights reserved.

  14. Metoclopramide as pharmacological tool to assess vasopressinergic co-activation of the hypothalamus-pituitary-adrenal (HPA) axis: a study in healthy volunteers.

    Science.gov (United States)

    Jacobs, G E; Hulskotte, E G J; de Kam, M L; Zha, G; Jiang, J; Hu, P; Zhao, Q; van Pelt, J; Goekoop, J G; Zitman, F G; van Gerven, J M A

    2010-12-01

    The synthetic vasopressin (AVP) analogue desmopressin (dDAVP) has been used as pharmacological function test to quantify vasopressinergic co-activation of the hypothalamus-pituitary-adrenal (HPA) axis in the past. Such exogenous vasopressinergic stimulation may induce confounding cardiovascular, pro-coagulatory and anti-diuretic effects and low endogenous corticotrophin-releasing-hormone (CRH) levels may limit its potential to reliably assess co-activation. Alternatively, the dopamine-2-(D2)-antagonist metoclopramide is believed to induce co-activation indirectly by releasing endogenous AVP. We investigated this indirect co-activation with metoclopramide under conditions of low and enhanced endogenous CRH release in healthy volunteers. A randomized, double-blind, placebo-controlled, four-way crossover study was performed in 12 healthy males. CRH release was induced by administering an oral 5-hydroxytryptophan (5-HTP) 200 mg function test. Co-activation was investigated by administering metoclopramide 10mg intravenously around the expected maximal effect of 5-HTP. The neuroendocrine effects were compared to those of metoclopramide alone, the 5-HTP test alone and matching placebo. Metoclopramide safely induced HPA-axis activation by itself, and potently synergized 5-HTP-induced corticotrophinergic activation of the HPA axis. These findings are indicative of vasopressinergic co-activation and suggest a role for metoclopramide as a practical function test for co-activation of the HPA axis. However, its application will be hampered pending clarification of the exact pharmacological mechanism by which metoclopramide induces co-activation of the HPA axis.

  15. 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

  16. Up-regulation of the fetal baboon hypothalamo-pituitary-adrenal axis in intrauterine growth restriction: coincidence with hypothalamic glucocorticoid receptor insensitivity and leptin receptor down-regulation.

    Science.gov (United States)

    Li, Cun; Ramahi, Emma; Nijland, Mark J; Choi, Jaeyhek; Myers, Dean A; Nathanielsz, Peter W; McDonald, Thomas J

    2013-07-01

    Intrauterine growth restriction (IUGR) is an important fetal developmental problem resulting from 2 broad causes: maternal undernutrition and/or decreased fetal nutrient delivery to the fetus via placental insufficiency. IUGR is often accompanied by up-regulation of the hypothalamo-pituitary-adrenal axis (HPAA). Sheep studies show fetal HPAA autonomy in late gestation. We hypothesized that IUGR, resulting from poor fetal nutrient delivery, up-regulates the fetal baboon HPAA in late gestation, driven by hypothalamo-pituitary glucocorticoid receptor (GR) insensitivity and decreased fetal leptin in peripheral plasma. Maternal baboons were fed as ad libitum controls or nutrient restricted to produce IUGR (fed 70% of the control diet) from 0.16 to 0.9 gestation. Peripheral ACTH, cortisol, and leptin were measured by immunoassays. CRH, arginine vasopressin (AVP), GR, leptin receptor (ObRb), and pro-opiomelanocortin peptide expression were determined immunohistochemically. IUGR fetal peripheral cortisol and ACTH, but not leptin, were increased (P HPAA activation was aided by GR insensitivity and decreased ObRb expression in the PVN, and (3) the anterior pituitary is not a site for ObRb effects on the HPAA.

  17. Chlorella vulgaris reduces the impact of stress on hypothalamic-pituitary-adrenal axis and brain c-fos expression.

    Science.gov (United States)

    Souza Queiroz, Julia; Marín Blasco, Ignacio; Gagliano, Humberto; Daviu, Nuria; Gómez Román, Almudena; Belda, Xavier; Carrasco, Javier; Rocha, Michelle C; Palermo Neto, João; Armario, Antonio

    2016-03-01

    Predominantly emotional stressors activate a wide range of brain areas, as revealed by the expression of immediate early genes, such as c-fos. Chlorella vulgaris (CV) is considered a biological response modifier, as demonstrated by its protective activities against infections, tumors and stress. We evaluated the effect of acute pretreatment with CV on the peripheral and central responses to forced swimming stress in adult male rats. Pretreatment with CV produced a significant reduction of stress-related hypothalamic-pituitary-adrenal activation, demonstrated by decreased corticotrophin releasing factor gene expression in the hypothalamic paraventricular nucleus (PVN) and lower ACTH response. Hyperglycemia induced by the stressor was similarly reduced. This attenuated neuroendocrine response to stress occurred in parallel with a diminished c-fos expression in most evaluated areas, including the PVN. The data presented in this study reinforce the usefulness of CV to diminish the impact of stressors, by reducing the HPA response. Although our results suggest a central effect of CV, further studies are necessary to understand the precise mechanisms underpinning this effect.

  18. Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals

    NARCIS (Netherlands)

    Huizenga, NATM; Koper, JW; De Lange, P; Pols, HAP; Stolk, RP; Grobbee, DE; De Jong, FH; Lamberts, SWJ

    1998-01-01

    In the present study, we investigated whether the negative feedback action of glucocorticoids (GCs) on the hypothdamo-pituitary-adrenal (HPA) axis changes with age. We performed a 1-mg dexamethasone (DEX) suppression test in 216 healthy elderly individuals. To investigate individual variability of f

  19. Can variation in hypothalamic-pituitary-adrenal (HPA-axis activity explain the relationship between depression and cognition in bipolar patients?

    Directory of Open Access Journals (Sweden)

    Marieke J van der Werf-Eldering

    Full Text Available BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning. METHODOLOGY/PRINCIPAL FINDINGS: In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition. CONCLUSIONS/SIGNIFICANCE: As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship.

  20. Sex differences in early-life programming of the hypothalamic-pituitary-adrenal axis in humans suggest increased vulnerability in females: a systematic review.

    Science.gov (United States)

    Carpenter, T; Grecian, S M; Reynolds, R M

    2017-04-01

    Fetal glucocorticoid overexposure is a key mechanism linking early development with later-life disease. In humans, low birth weight associates with increased fasting cortisol, hypothalamic-pituitary-adrenal (HPA) axis reactivity, and with cardiovascular risk and cognitive decline. As there are sex differences in these adult diseases, we hypothesized that there may be sex differences in programming of the HPA axis in response to prenatal stressors. We conducted a systematic review following Meta-Analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analysis. We searched Embase, MEDLINE and Web of Science from inception to 31 October 2016. We included studies related to sex differences, prenatal exposures and HPA axis. We excluded studies investigating specific disease states. The 23 included studies investigated the consequences of low birth weight, preterm birth and maternal stressors of asthma, psychosocial stress and glucocorticoid medications on HPA axis outcomes of placental glucocorticoid biology and offspring HPA axis function in early life and later life. Female offspring exposed to stressors had increased HPA axis reactivity compared with males. Furthermore, the female placenta increased its permeability to maternal glucocorticoids following maternal stress with changes in the expression of 11β-hydroxysteroid dehydrogenase enzymes in response to maternal glucocorticoid exposure or asthma. Among males there was some evidence of altered diurnal cortisol secretion. We conclude that although there is some evidence of male vulnerability leading to altered diurnal cortisol secretion, the female HPA axis is more vulnerable to programming, particularly in terms of its reactivity; this suggests a mechanism underlying sex differences in later-life diseases.

  1. Immediate and prolonged effects of alcohol exposure on the activity of the hypothalamic-pituitary-adrenal axis in adult and adolescent rats

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    ALLEN, Camryn D.; LEE, Soon; KOOB, George F.; RIVIER, Catherine

    2011-01-01

    Alcohol stimulates the hypothalamic-pituitary-adrenal (HPA) axis. Part of this influence is likely exerted directly at the level of the corticotropin-releasing factor (CRF) gene, but intermediates may also play a role. Here we review the effect of alcohol on this axis, provide new data on the effects of binge drinking during adolescence, and argue for a role of catecholaminergic circuits. Indeed, acute injection of this drug activates brain stem adrenergic and noradrenergic circuits, and their lesion, or blockade of α1 adrenergic receptors significantly blunts alcohol-induced ACTH release. As alcohol can influence the HPA axis even once discontinued, and alcohol consumption in young people is associated with increased adult drug abuse (a phenomenon possibly mediated by the HPA axis), we determined whether alcohol consumption during adolescence modified this axis. The number of CRF-immunoreactive (ir) cells/section was significantly decreased in the central nucleus of the amygdala of adolescent self-administering binge-drinking animals, compared to controls. When another group of adolescent binge-drinking rats was administered alcohol in adulthood, the number of colocalized c-fos-ir and PNMT-ir cells/brain stem section in the C3 area was significantly decreased, compared to controls. As the HPA axis response to alcohol is blunted in adult rats exposed to alcohol vapors during adolescence, a phenomenon which was not observed in our model of self-administration, it is possible that the blood alcohol levels achieved in various models play a role in the long-term consequences of exposure to alcohol early in life. Collectively, these results suggest an important role of brain catecholamines in modulating the short- and long-term consequences of alcohol administration. PMID:21300146

  2. Neuroregulation of the Hypothalamus-Pituitary-Adrenal (HPA Axis in Humans: Effects of GABA-, Mineralocorticoid-, and GH-Secretagogue-Receptor Modulation

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    Roberta Giordano

    2006-01-01

    Full Text Available The hypothalamus-pituitary-adrenal (HPA axis exerts a variety of effects at both the central and peripheral level. Its activity is mainly regulated by CRH, AVP, and the glucocorticoid-mediated feedback action. Moreover, many neurotransmitters and neuropeptides influence HPA axis activity by acting at the hypothalamic and/or suprahypothalamic level. Among them, GABA and Growth Hormone Secretagogues (GHS/GHS-receptor systems have been shown to exert a clear inhibitory and stimulatory effect, respectively, on corticotroph secretion. Alprazolam (ALP, a GABA-A receptor agonist, shows the most marked inhibitory effect on both spontaneous and stimulated HPA axis activity, in agreement with its peculiar efficacy in panic disorders and depression where an HPA axis hyperactivation is generally present. Ghrelin and synthetic GHS possess a marked ACTH/cortisol-releasing effect in humans and the ghrelin/GHS-R system is probably involved in the modulation of the HPA response to stress and nutritional/metabolic variations. The glucocorticoid-mediated negative feedback action is mediated by both glucocorticoid (GR and mineralocorticoid (MR receptors activation at the central level, mainly in the hippocampus. In agreement with animal studies, MRs seem to play a crucial role in the maintenance of the circadian ACTH and cortisol rhythm, through the modulation of CRH and AVP release. GABA agonists (mainly ALP, ghrelin, as well as MR agonists/antagonists, may represent good tools to explore the activity of the HPA axis in both physiological conditions and pathological states characterized by an impaired control of the corticotroph function.

  3. Fetal alcohol exposure alters proopiomelanocortin gene expression and hypothalamic-pituitary-adrenal axis function via increasing MeCP2 expression in the hypothalamus.

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    Omkaram Gangisetty

    Full Text Available Proopiomelanocortin (POMC is a precursor gene of the neuropeptide β-endorphin in the hypothalamus and is known to regulate various physiological functions including stress response. Several recent reports showed that fetal alcohol exposure programs the hypothalamus to produce lower levels of POMC gene transcripts and to elevate the hypothalamic-pituitary-adrenal (HPA axis response to stressful stimuli. We investigated the role of methyl CpG binding protein (MeCP2 in the effects of prenatal ethanol on POMC gene expression and hypothalamic-pituitary-adrenal (HPA axis function. Pregnant Sprague Dawley rats were fed between GD 7 and 21 with a liquid diet containing 6.7% alcohol, pair-fed with isocaloric liquid diet, or fed ad libitum with rat chow, and their male offsprings were used at 60 days after birth in this study. Fetal alcohol exposure reduced the level of POMC mRNA, but increased the level of DNA methylation of this gene in the arcuate nucleus (ARC of the hypothalamus where the POMC neuronal cell bodies are located. Fetal alcohol exposed rats showed a significant increase in MeCP2 protein levels in POMC cells, MeCP2 gene transcript levels as well as increased MeCP2 protein binding on the POMC promoter in the arcuate nucleus. Lentiviral delivery of MeCP2 shRNA into the third ventricle efficiently reduced MeCP2 expression and prevented the effect of prenatal ethanol on POMC gene expression in the arcuate nucleus. MeCP2-shRNA treatment also normalized the prenatal ethanol-induced increase in corticotropin releasing hormone (CRH gene expression in the hypothalamus and elevated plasma adrenocorticotrophic hormone (ACTH and corticosterone hormone responses to lipopolysaccharide (LPS challenge. These results suggest that fetal alcohol programming of POMC gene may involve recruitment of MeCP2 on to the methylated promoter of the POMC gene to suppress POMC transcript levels and contribute to HPA axis dysregulation.

  4. Positive environmental modification of depressive phenotype and abnormal hypothalamic-pituitary-adrenal axis activity in female C57BL/6J mice during abstinence from chronic ethanol consumption

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    Terence Y Pang

    2013-07-01

    Full Text Available Depression is a commonly reported co-morbidity during rehabilitation from alcohol use disorders and its presence is associated with an increased likelihood of relapse. Interventions which impede the development of depression could be of potential benefit if incorporated into treatment programs. We previously demonstrated an ameliorative effect of physical exercise on depressive behaviours in a mouse model of alcohol abstinence. Here, we show that environmental enrichment (cognitive and social stimulation has a similar beneficial effect. The hypothalamic-pituitary-adrenal (HPA axis is a key physiological system regulating stress responses and its dysregulation has been separably implicated in the pathophysiology of depression and addiction disorders. We performed a series of dexamethasone challenges and found that mice undergoing 2 weeks of alcohol abstinence had significantly greater corticosterone and ACTH levels following a DEX-CRH challenge compared to water controls. Environmental enrichment during alcohol abstinence corrected the abnormal DEX-CRH corticosterone response despite a further elevation of ACTH levels. Examination of gene expression revealed abstinence-associated alterations in glucocorticoid receptor (Gr, corticotrophin releasing hormone (Crh and pro-opiomelanocortin (Pomc1 mRNA levels which were differentially modulated by environmental enrichment. Overall, our study demonstrates a benefit of environmental enrichment on alcohol abstinence-associated depressive behaviours and HPA axis dysregulation.

  5. Exploration of the Hypothalamic-Pituitary-Adrenal Axis to Improve Animal Welfare by Means of Genetic Selection: Lessons from the South African Merino.

    Science.gov (United States)

    Hough, Denise; Swart, Pieter; Cloete, Schalk

    2013-05-17

    It is a difficult task to improve animal production by means of genetic selection, if the environment does not allow full expression of the animal's genetic potential. This concept may well be the future for animal welfare, because it highlights the need to incorporate traits related to production and robustness, simultaneously, to reach sustainable breeding goals. This review explores the identification of potential genetic markers for robustness within the hypothalamic-pituitary-adrenal axis (HPAA), since this axis plays a vital role in the stress response. If genetic selection for superior HPAA responses to stress is possible, then it ought to be possible to breed robust and easily managed genotypes that might be able to adapt to a wide range of environmental conditions whilst expressing a high production potential. This approach is explored in this review by means of lessons learnt from research on Merino sheep, which were divergently selected for their multiple rearing ability. These two selection lines have shown marked differences in reproduction, production and welfare, which makes this breeding programme ideal to investigate potential genetic markers of robustness. The HPAA function is explored in detail to elucidate where such genetic markers are likely to be found.

  6. Exploration of the Hypothalamic-Pituitary-Adrenal Axis to Improve Animal Welfare by Means of Genetic Selection: Lessons from the South African Merino

    Directory of Open Access Journals (Sweden)

    Schalk Cloete

    2013-05-01

    Full Text Available It is a difficult task to improve animal production by means of genetic selection, if the environment does not allow full expression of the animal’s genetic potential. This concept may well be the future for animal welfare, because it highlights the need to incorporate traits related to production and robustness, simultaneously, to reach sustainable breeding goals. This review explores the identification of potential genetic markers for robustness within the hypothalamic-pituitary-adrenal axis (HPAA, since this axis plays a vital role in the stress response. If genetic selection for superior HPAA responses to stress is possible, then it ought to be possible to breed robust and easily managed genotypes that might be able to adapt to a wide range of environmental conditions whilst expressing a high production potential. This approach is explored in this review by means of lessons learnt from research on Merino sheep, which were divergently selected for their multiple rearing ability. These two selection lines have shown marked differences in reproduction, production and welfare, which makes this breeding programme ideal to investigate potential genetic markers of robustness. The HPAA function is explored in detail to elucidate where such genetic markers are likely to be found.

  7. A Role for the Androgen Metabolite, 5alpha androstane, 3beta, 17beta Diol (3b-DIol in the regulation of the hypothalamo-pituitary-adrenal axis.

    Directory of Open Access Journals (Sweden)

    Robert James Handa

    2011-11-01

    Full Text Available Activation of the hypothalamo-pituitary-adrenal (HPA axis is a basic reaction of animals to environmental perturbations that threaten homeostasis. These responses are ultimately regulated by neurons residing within the paraventricular nucleus of the hypothalamus (PVN. Within the PVN, corticotropin-releasing hormone (CRH, vasopressin (AVP and oxytocin (OT expressing neurons are critical as they can regulate both neuroendocrine and autonomic responses. Estradiol (E2 and testosterone (T are well known reproductive hormones, however, they have also been shown to modulate stress reactivity. In rodent models, evidence shows that under some conditions E2 enhances stress activated ACTH and corticosterone secretion. In contrast, T decreases the gain of the HPA axis. The modulatory role of testosterone was originally thought to be via 5 alpha reduction to the potent androgen, dihydrotestosterone, whereas E2 effects were thought to be mediated by both estrogen receptors alpha (ERα and beta (ERβ. However, DHT has been shown to be metabolized to the ERβ agonist, 5alpha- androstane 3beta,17beta diol (3b-Diol. The actions of 3β-Diol on the HPA axis are mediated by ERbeta which inhibits the PVN response to stressors. In gonadectomized rats, ERbeta agonists reduce CORT and ACTH responses to restraint stress, an effect that is also present in wild-type but not ERbeta knockout mice. The neurobiological mechanisms underlying the actions of ERbeta to alter HPA reactivity are not currently known. CRH, AVP and OT have all been shown to be regulated by estradiol and recent studies indicate an important role of ERbeta in these regulatory processes. Moreover, activation of the CRH and AVP promoters have been shown by 3β-Diol binding to ERbeta and this is thought to be through alternate pathways of gene regulation. Based on available data, a novel and important role for 3beta Diol in the regulation of the HPA axis is suggested.

  8. Multi-Level Risk Factors for Suicidal Ideation Among at-Risk Adolescent Females: The Role of Hypothalamic-Pituitary-Adrenal Axis Responses to Stress.

    Science.gov (United States)

    Giletta, Matteo; Calhoun, Casey D; Hastings, Paul D; Rudolph, Karen D; Nock, Matthew K; Prinstein, Mitchell J

    2015-07-01

    Adopting a multi-level approach, this study examined risk factors for adolescent suicidal ideation, with specific attention to (a) hypothalamic-pituitary-adrenal (HPA) axis stress responses and (b) the interplay between HPA-axis and other risk factors from multiple domains (i.e., psychological, interpersonal and biological). Participants were 138 adolescent females (M(age) = 14.13 years, SD = 1.40) at risk for suicidal behaviors. At baseline, lifetime suicidal ideation and a number of risk factors were assessed (i.e., depressive symptoms, impulsiveness, pubertal status and peer stress). Participants were exposed to a psychosocial stress task and HPA-axis responses were assessed by measuring cortisol levels pre- and post-stressor. At 3 months post-baseline, suicidal ideation again was assessed. Using group-based trajectory modeling, three groups of cortisol stress-response patterns were identified (i.e., hyporesponsive, normative, and hyperresponsive). As compared to females in the normative and hyporesponsive group, females in the hyperresponsive group were more likely to report a lifetime history of suicidal ideation at baseline, above and beyond the effects of the other predictors. Moreover, as compared to females in the normative group, females in the hyperresponsive group were at increased risk for reporting suicidal ideation 3 months later, after controlling for prior ideation. No interactions between cortisol group and the other risk factors were significant, with the exception of a non-significant trend between impulsiveness and cortisol group on lifetime suicidal ideation. Findings highlight the importance of HPA-axis responses to acute stressors as a risk factor for suicidal ideation among adolescents.

  9. Clinical insights into the safety and utility of the insulin tolerance test (ITT) in the assessment of the hypothalamo-pituitary-adrenal axis.

    LENUS (Irish Health Repository)

    Finucane, Francis M

    2008-10-01

    The insulin tolerance test (ITT) is the gold standard for assessing GH and cortisol production in pituitary disease. However, areas of uncertainty remain regarding its safety in older people, the optimal duration of the test and its performance in insulin resistant states. Whether basal cortisol concentration can reliably predict an adequate adrenal response to hypoglycaemia remains to be determined.

  10. Evidence against a critical role of CB1 receptors in adaptation of the hypothalamic-pituitary-adrenal axis and other consequences of daily repeated stress.

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    Rabasa, Cristina; Pastor-Ciurana, Jordi; Delgado-Morales, Raúl; Gómez-Román, Almudena; Carrasco, Javier; Gagliano, Humberto; García-Gutiérrez, María S; Manzanares, Jorge; Armario, Antonio

    2015-08-01

    There is evidence that endogenous cannabinoids (eCBs) play a role in the control of the hypothalamic-pituitary-adrenal (HPA) axis, although they appear to have dual, stimulatory and inhibitory, effects. Recent data in rats suggest that eCBs, acting through CB1 receptors (CB1R), may be involved in adaptation of the HPA axis to daily repeated stress. In the present study we analyze this issue in male mice and rats. Using a knock-out mice for the CB1 receptor (CB1-/-) we showed that mutant mice presented similar adrenocorticotropic hormone (ACTH) response to the first IMO as wild-type mice. Daily repeated exposure to 1h of immobilization reduced the ACTH response to the stressor, regardless of the genotype, demonstrating that adaptation occurred to the same extent in absence of CB1R. Prototypical changes observed after repeated stress such as enhanced corticotropin releasing factor (CRH) gene expression in the paraventricular nucleus of the hypothalamus, impaired body weight gain and reduced thymus weight were similarly observed in both genotypes. The lack of effect of CB1R in the expression of HPA adaptation to another similar stressor (restraint) was confirmed in wild-type CD1 mice by the lack of effect of the CB1R antagonist AM251 just before the last exposure to stress. Finally, the latter drug did not blunt the HPA, glucose and behavioral adaptation to daily repeated forced swim in rats. Thus, the present results indicate that CB1R is not critical for overall effects of daily repeated stress or proper adaptation of the HPA axis in mice and rats.

  11. 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

  12. Dysregulation of the hypothalamus-pituitary-adrenal axis predicts some aspects of the behavioral response to chronic fluoxetine: association with hippocampal cell proliferation

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    Wahid eKhemissi

    2014-09-01

    Full Text Available In depressed patients, antidepressant resistance has been associated with dysregulation of the hypothalamus-pituitary-adrenal (HPA axis but the underlying mechanisms are poorly understood. The scope of this study was to try to create HPA-related antidepressant resistance in mice and to investigate adult hippocampal neurogenesis as a putative mechanism of antidepressant resistance. Mice were subjected to a 9 week Unpredictable Chronic Mild Stress (UCMS. After a 2 weeks drug-free period, mice were segregated in two groups, according to the percentage of corticosterone suppression after dexamethasone injection: High suppression (HS and Low suppression (LS mice. From the 5thweek onwards, fluoxetine at a dose of 15 mg/kg (i.p. was administered daily and at the end of 8th week, a battery of behavioral tests assessing the emotional, cognitive, and motor aspects of UCMS-induced depressive-like behavior was applied. Results show that fluoxetine-induced antidepressant effects were observed with higher amplitude in HS when compared to LS on various behavioral phenotypes, like coat state, novelty suppression of feeding, splash test and nest test. The same profile was found concerning the immunohistochimical analysis of ki-67 positive cells in the dentate gyrus of the hippocampus, which is a marker of neuronal proliferation, but not for doublecortin labelling. This suggests that the failure of fluoxetine to induce antidepressant effects may be associated to the poor ability of the compound to stimulate cell proliferation in the hippocampus.

  13. Environmental enrichment mitigates the sex-specific effects of gestational inflammation on social engagement and the hypothalamic pituitary adrenal axis-feedback system.

    Science.gov (United States)

    Connors, E J; Shaik, A N; Migliore, M M; Kentner, A C

    2014-11-01

    Modest environmental enrichment (EE) is well recognized to protect and rescue the brain from the consequences of a variety of insults. Although animal models of maternal immune activation (MIA) are associated with several neurodevelopmental impairments in both the behavioral and cognitive functioning of offspring, the impact of EE in protecting or reversing these effects has not been fully evaluated. In the present study, female Sprague-Dawley rats were randomized into EE (pair-housed in a large multi-level cage with toys, tubes and ramps) or animal care control (ACC; pair-housed in standard cages) conditions. Each pair was bred, following assignment to their housing condition, and administered 100μg/kg of lipopolysaccharide (LPS) on gestational day 11. After birth, and until the end of the study, offspring were maintained in their respective housing conditions. EE protected against both the social and hypothalamic pituitary adrenal axis consequences of MIA in juvenile male rats, but surprisingly not against the spatial discrimination deficits or accompanying decrease in glutamate levels within the hippocampus (as measured via LCMS-MS). Based on these preliminary results, the mechanisms that underlie the sex-specific consequences that follow MIA appear to be dependent on environmental context. Together, this work highlights the importance of environmental complexity in the prevention of neurodevelopmental deficits following MIA.

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

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    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.

  15. [Influence of interleukin-1 and interleukin-6 on modulation of hypothalamo-pituitary-adrenal axis in pregnancy at term and in spontaneous and oxytocin-induced delivery].

    Science.gov (United States)

    Ochedalski, Tomasz; Lachowicz, Agnieszka

    2003-10-01

    During the pregnancy the placenta and hypothalamus produce trophic hormones for hypothalamo-pituitary-adrenal axis (HPA), i.e. corticotropin releasing hormone (CRH) and adrenocorticotropin (ACTH). The HPA axis of pregnant women is differentially modulated in comparison to non-pregnant ones. Beside steroids, the influence on CRH release may be modulated by cytokines, especially interleukin 1 (IL-1) and interleukin 6 (IL-6). To evaluate the effects of IL-1 and IL-6 on modulation of HPA axis in pregnancy, we have examined the group of women with spontaneous delivery, and second group consists of women delivered after intravenous oxytocin infusion. All women were at term and in the same pregnancy age. Blood was sampled from a maternal peripheral vein days before labour, during the second stage of labour and on the second postnatal day, the levels of IL-1, IL-6, CRH, ACTH and cortisol were measured. The concentrations of hormones were measured using RIA method. The level of IL-1 before the delivery was significantly higher in the group with oxytocin-induction. CRH concentration before the labour was much higher in the group with spontaneous contractions. The levels of IL-1 and CRH in both groups decreased during the labour and were lowest after the delivery. Concentration of IL-6 did not changed dependently of group and time of blood sampling. Changes in CRH in time concentration did not correlate with changes in ACTH levels. ACTH concentrations were similar in both groups, low before delivery raised during the delivery and low again after labour. Cortisol concentration in spontaneous labour was much lower before delivery in comparison with second examined group, then lowered during and after the delivery. In group with oxytocin induction, cortisol levels raised during the delivery and maintained almost the same level after the labour. The time-changes in IL-1 concentration and ACTH and cortisol levels were similar in shape in group with spontaneous delivery. These

  16. Cortisol reactivity and suicidal behavior: Investigating the role of hypothalamic-pituitary-adrenal axis responses to stress in suicide attempters and ideators.

    Science.gov (United States)

    O'Connor, Daryl B; Green, Jessica A; Ferguson, Eamonn; O'Carroll, Ronan E; O'Connor, Rory C

    2017-01-01

    Every 40s a person dies by suicide somewhere in the world. The causes of suicidal behavior are not fully understood. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, is one potential risk factor. The current study aimed to investigate whether cortisol reactivity to a laboratory stress task differentiated individuals who had previously made a suicide attempt from those who had thought about suicide (suicide ideators) and control participants. One hundred and sixty participants were recruited to a previous attempt, a suicidal ideation or a control group. Participants completed background questionnaires before completing the Maastricht Acute Stress Test (MAST). Cortisol levels were assessed throughout the stress task. Measures of suicide behavior were measured at baseline, 1 month and 6 month follow-up. Participants who had made a previous suicide attempt exhibited significantly lower aggregate cortisol levels during the MAST compared to participants in the control group; suicide ideators were intermediate to both groups. This effect, however, was driven by participants who made an attempt within the past year, and to some degree by those with a family history of attempt. Participants who made a suicide attempt and had a family history of suicide exhibited the lowest levels of cortisol in response to stress. Finally, lower levels of cortisol in response to the MAST were associated with higher levels of suicidal ideation at 1-month follow-up in the suicide attempter group. These results are consistent with other findings indicating that blunted HPA axis activity is associated with some forms of suicidal behavior. The challenge for researchers is to elucidate the precise causal mechanisms linking stress, cortisol and suicide risk.

  17. Effect of continuous positive airway pressure therapy on hypothalamic-pituitary-adrenal axis function and 24-h blood pressure profile in obese men with obstructive sleep apnea syndrome.

    Science.gov (United States)

    Carneiro, Gláucia; Togeiro, Sônia Maria; Hayashi, Lílian F; Ribeiro-Filho, Fernando Flexa; Ribeiro, Artur Beltrame; Tufik, Sérgio; Zanella, Maria Teresa

    2008-08-01

    Obstructive sleep apnea syndrome (OSAS) increases the risk of cardiovascular events. Sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis activation may be the mechanism of this relationship. The aim of this study was to evaluate HPA axis and ambulatory blood pressure monitoring in obese men with and without OSAS and to determine whether nasal continuous positive airway pressure therapy (nCPAP) influenced responses. Twenty-four-hour ambulatory blood pressure monitoring and overnight cortisol suppression test with 0.25 mg of dexamethasone were performed in 16 obese men with OSAS and 13 obese men controls. Nine men with severe apnea were reevaluated 3 mo after nCPAP therapy. Body mass index and blood pressure of OSAS patients and obese controls were similar. In OSAS patients, the percentage of fall in systolic blood pressure at night (P = 0.027) and salivary cortisol suppression postdexamethasone (P = 0.038) were lower, whereas heart rate (P = 0.022) was higher compared with obese controls. After nCPAP therapy, patients showed a reduction in heart rate (P = 0.036) and a greater cortisol suppression after dexamethasone (P = 0.001). No difference in arterial blood pressure (P = 0.183) was observed after 3 mo of nCPAP therapy. Improvement in cortisol suppression was positively correlated with an improvement in apnea-hypopnea index during nCPAP therapy (r = 0.799, P = 0.010). In conclusion, men with OSAS present increased postdexamethasone cortisol levels and heart rate, which were recovered by nCPAP.

  18. Early life stress in depressive patients: role of glucocorticoid and mineralocorticoid receptors and of hypothalamic-pituitary-adrenal axis activity.

    Science.gov (United States)

    Juruena, Mario Francisco; Werne Baes, Cristiane Von; Menezes, Itiana Castro; Graeff, Frederico Guilherme

    2015-01-01

    Depression is a chronic, recurrent and long-term disorder characterized by high rates of impairment and several comorbidities. Early life stress (ELS) is associated with the increased risk for developing depression in adulthood, influences its clinical course and predicts a poorer treatment outcome. Stressful life events play an important role in the pathogenesis of depression, being well established as acute triggers of psychiatric illness. The vulnerability for developing depression is associated to changes in neurobiological systems related to stress regulation. The hypothalamic-pituitaryadrenal (HPA) axis responds to external and internal stimuli. Reported results indicate that stress in early phases of development can induce persistent changes in the response of the HPA axis to stress in adulthood, leading to a raised susceptibility to depression. These abnormalities appear to be related to the HPA axis deregulation in depression, partially due to an imbalance between glucocorticoid receptors (GR) and mineral ocorticoid receptors (MR). While most studies have consistently demonstrated that GR function is impaired in major depression (reduced GR-mediated feedback in HPA axis), data about the MR role in depression are still limited and contr oversial. Thus, in this review article we summarize the main reported findings about the consequences of ELS in HPA axis functioning and in the responsivity of MR/GR receptors in depression.

  19. Effects of atrazine (ATR), deisopropylatrazine (DIA), Diaminochlorotriazine (DACT) on the hypothalamic-pituitary-adrenal (HPA) axis in female rats

    Science.gov (United States)

    We previously reported that a single dose of the herbicide ATR stimulated the HPA axis in the male rat while equimolar doses of its primary metabolite, DACT, had a minimal effect. In this study, we evaluated the effects of one or four daily doses of ATR, DACT, and an intermediat...

  20. EFFECTS OF ATRAZINE (ATR), DEISOPROPYLATRAZINE (DIA), AND DIAMINOCHLOROTRIAZINE (DACT) ON THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS IN FEMALE RATS

    Science.gov (United States)

    Previously we reported that a single dose of ATR herbicide stimulated HPA axis activation in the male rat while its primary metabolite, DACT, did so to a lesser extent. In this study, we evaluated the effects of ATR, DACT, and an intermediate metabolite, DIA, on adrenocorticotrop...

  1. Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation

    Directory of Open Access Journals (Sweden)

    Jong-Ho Lee

    2014-06-01

    Full Text Available BackgroundThis study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF during adolescence on the adverse behavioral outcome of neonatal maternal separation.MethodsMale Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS or left undisturbed (nonhandled, NH. Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF. Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay.ResultsDaily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it.ConclusionProlonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA axis.

  2. Acute heat stress impairs performance parameters and induces mild intestinal enteritis in broiler chickens: role of acute hypothalamic-pituitary-adrenal axis activation.

    Science.gov (United States)

    Quinteiro-Filho, W M; Rodrigues, M V; Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Sá, L R M; Ferreira, A J P; Palermo-Neto, J

    2012-06-01

    Studies on the environmental consequences of stress are relevant for economic and animal welfare reasons. We recently reported that long-term heat stressors (31 ± 1°C and 36 ± 1°C for 10 h/d) applied to broiler chickens (Gallus gallus domesticus) from d 35 to 42 of life increased serum corticosterone concentrations, decreased performance variables and the macrophage oxidative burst, and produced mild, multifocal acute enteritis. Being cognizant of the relevance of acute heat stress on tropical and subtropical poultry production, we designed the current experiment to analyze, from a neuroimmune perspective, the effects of an acute heat stress (31 ± 1°C for 10 h on d 35 of life) on serum corticosterone, performance variables, intestinal histology, and peritoneal macrophage activity in chickens. We demonstrated that the acute heat stress increased serum corticosterone concentrations and mortality and decreased food intake, BW gain, and feed conversion (P 0.05). Increases in the basal and the Staphylococcus aureus-induced macrophage oxidative bursts and a decrease in the percentage of macrophages performing phagocytosis were also observed. Finally, mild, multifocal acute enteritis, characterized by the increased presence of lymphocytes and plasmocytes within the lamina propria of the jejunum, was also observed. We found that the stress-induced hypothalamic-pituitary-adrenal axis activation was responsible for the negative effects observed on chicken performance and immune function as well as for the changes in the intestinal mucosa. The data presented here corroborate with those presented in other studies in the field of neuroimmunomodulation and open new avenues for the improvement of broiler chicken welfare and production performance.

  3. Effects of early- and late-gestational maternal stress and synthetic glucocorticoid on development of the fetal hypothalamus-pituitary-adrenal axis in sheep.

    Science.gov (United States)

    Rakers, Florian; Frauendorf, Vilmar; Rupprecht, Sven; Schiffner, Rene; Bischoff, Sabine J; Kiehntopf, Michael; Reinhold, Petra; Witte, Otto W; Schubert, Harald; Schwab, Matthias

    2013-01-01

    Prenatal maternal stress (PMS) programs dysregulation of the hypothalamus-pituitary-adrenal axis (HPAA) in postnatal life, though time periods vulnerable to PMS, are still unclear. We evaluated in pregnant sheep the effect of PMS during early gestation [30-100 days of gestation (dGA); term is 150 dGA] or late gestation (100-120 dGA) on development of fetal HPAA function. We compared the effects of endogenous cortisol with synthetic glucocorticoid (GC) exposure, as used clinically to enhance fetal lung maturation. Pregnant sheep were exposed to repeated isolation stress twice per week for 3 h in a separate box with no visual, tactile, or auditory contact with their flock-mates either during early (n = 7) or late (n = 7) gestation. Additional groups received two courses of betamethasone (BM; n = 7; 2 × 110 μg kg(- 1) body weight, 24 h apart) during late gestation (106/107 and 112/113 dGA, n = 7) or acted as controls (n = 7). Fetal cortisol responses to hypotensive challenge, a physiological fetal stressor, were measured at 112 and 129 dGA, i.e. before and during maturation of the HPAA. Hypotension was induced by fetal infusion of sodium nitroprusside, a potent vasodilator. At 112 dGA, neither PMS nor BM altered fetal cortisol responses. PMS, during early or late gestation, and BM treatment increased fetal cortisol responses at 129 dGA with the greatest increase achieved in stressed early pregnant sheep. Thus, development of the HPAA is vulnerable to inappropriate levels of GCs during long periods of fetal life, whereas early gestation is most vulnerable to PMS.

  4. Blunted hypothalamic-pituitary-adrenal axis and insulin response to psychosocial stress in young adults born preterm at very low birth weight.

    Science.gov (United States)

    Kaseva, Nina; Wehkalampi, Karoliina; Pyhälä, Riikka; Moltchanova, Elena; Feldt, Kimmo; Pesonen, Anu-Katriina; Heinonen, Kati; Hovi, Petteri; Järvenpää, Anna-Liisa; Andersson, Sture; Eriksson, Johan G; Räikkönen, Katri; Kajantie, Eero

    2014-01-01

    Young adults born preterm at very low birth weight (VLBW, ≤1500 g) have higher levels of cardiovascular risk factors, including impaired glucose regulation, than their term-born peers. This could be mediated through altered hypothalamic-pituitary-adrenal axis (HPAA) response to stress. To compare HPAA, glucose and insulin responses provoked by psychosocial stress in VLBW subjects versus a comparison group of term-born controls. We studied 54 unimpaired young adults, aged 19-27 years, born at VLBW and a comparison group of 40 adults born at term, group-matched for age, sex and birth hospital, from one regional centre in southern Finland. The participants underwent a standardized psychosocial stress test (Trier Social Stress Test, TSST). In conjunction with TSST, we measured salivary cortisol, plasma ACTH, cortisol, glucose and insulin. Data were analysed with mixed-effects model and multiple linear regression analyses. Baseline concentrations for cortisol, ACTH, insulin and glucose were similar in VLBW and comparison groups. During TSST, analysed with mixed-effects model, overall concentrations of plasma cortisol were 17·2% lower (95% CI; 3·5 to 28·9) in the VLBW group. The VLBW group also had lower salivary (P = 0·04) and plasma cortisol (P = 0·02) responses to TSST. Insulin and glucose concentrations correlated with changes in cortisol concentrations. Accordingly, VLBW subjects had 26·5% lower increment in insulin (95% CI; 9·8-40·1). Analyses were adjusted for age, sex, body mass index, hormonal contraception, menstrual cycle phase, time of day and parental education. VLBW adults have lower HPAA responses to psychosocial stress than term-born controls. This is accompanied by a lower insulin response. © 2013 John Wiley & Sons Ltd.

  5. Adaptation of the pituitary-adrenal axis to daily repeated forced swim exposure in rats is dependent on the temperature of water.

    Science.gov (United States)

    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.

  6. Development of the adrenal axis in the neonatal rat

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, Ronnie [Univ. of Rochester, NY (United States)

    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)

  7. [Effects of blockage of hypothalamic-pituitary-adrenal cortex axis by metyrapone and Jiawei Xiaoyao Pills on immune system in mice exposed to chronic emotional stress].

    Science.gov (United States)

    Zhang, Yun; Wu, Zhen-Yu; Xiao, Jian; Geng, Xiao-Feng; Guo, Yan-Xia; Li, Shi-Jie

    2006-07-01

    To explore the effects of Jiawei Xiaoyao Pills (JWXYP) on immune system of mice exposed to chronic emotional stress, and to compare its effects with blockage of hypothalamic-pituitary-adrenal cortex axis (HPAA) by metyrapone. Eighty male mice were randomly divided into eight groups: normal saline-treated group, normal saline-treated stress group, JWXYP-treated group, JWXYP-treated stress group, metyrapone-treated group, metyrapone-treated stress group, metyrapone and JWXYP-treated group and metyrapone and JWXYP-treated stress group. A box of electrical shock was used to induce chronic emotional stress in mice. The metyrapone was applied to blocking the HPAA. The JWXYP, a classical formula of traditional Chinese medicine, which can alleviate the damages caused by chronic emotional stress, was also used to compare its effects with that of metyrapone. The body weight, thymus index, rate of apoptosis in thymus, serum concentration of glucocorticoid, activity of natural killer cells, lymphocyte transmission rate of mice were all measured and examined after interventions. The pathological changes of thymus tissue were observed. The thymus index, activity of natural killer cells and lymphocyte transmission rate were lower while the rate of apoptosis in thymus as well as the severity degree of pathological damages in thymus tissue were increased in the different drug-treated stress groups as compared with those in the corresponding drug-treated groups without stress. The activity of natural killer cells and the lymphocyte transmission rate induced by lipopolysaccharide were increased while the serum concentration of glucocorticoid and the severity degree of pathological damages in thymus tissue were decreased in both the metyrapone-treated stress group and JWXYP-treated stress group as compared with those in the normal saline-treated stress group. The combined intervention of metyrapone and JWXYP did not show better effects on immune system in mice exposed to chronic

  8. Chronic stress adaptation of the nitric oxide synthases and IL-1β levels in brain structures and hypothalamic-pituitary-adrenal axis activity induced by homotypic stress.

    Science.gov (United States)

    Gadek-Michalska, A; Tadeusz, J; Rachwalska, P; Bugajski, J

    2015-06-01

    β level in response to homotypic stress after 3 days and after 14 days. The present results indicate time-related similarities in the potent alterations in IL-1β and iNOS protein levels in brain structures. Single restraint induced a significant increase of plasma IL-1β level which was abolished by pretreatment with IL-1 receptor antagonist (IL-1Ra). A parallel strong increase of plasma ACTH and corticosterone levels were significantly impaired by IL-1Ra suggesting a marked involvement of stress-induced stimulation of ACTH and corticosterone by IL-1β in single restraint. In repeatedly restrained rats IL-1Ra significantly blunted plasma IL-1β level induced by homotypic stress. A parallel strong increase in plasma ACTH level by homotypic stress was not substantially altered by pretreatment with IL-1Ra in repeatedly stressed rats. Plasma a corticosterone level increased by homotypic stress in rats restrained for 3 and 14 days was not affected by pretreatment with IL-1Ra, but after for 7 days its level was significantly enhanced. These results suggest that repeated stress desensitizes IL-1β-induced stimulatory component in a single restraint stress-induced hypothalamic-pituitary-adrenal (HPA) axis stimulation. A sensitization by homotypic stress of corticosterone response after restraint for 7 days may depend on other stimulatory systems acting within adrenal glands during prolonged stress. Comparative data from the same model of rather mild psychological stress allows for the comparison of functional adaptive changes of NO synthases and IL-1β in brain structures involved in stress regulation. In general, the iNOS system is strongly sensitized by repeated stress for 3 days in prefrontal cortex and hippocampus. Increased plasma IL-1β level by a single restraint stress is significantly involved in ACTH and corticosterone secretion. Repeated stress for 3-14 days reduces this participation of IL-1β in pituitary-adrenal stimulation.

  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. 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.

  11. Reducing treatments in cattle superovulation protocols by combining a pituitary extract with a 5% hyaluronan solution: Is it able to diminish activation of the hypothalamic pituitary adrenal axis compared to the traditional protocol?

    Science.gov (United States)

    Biancucci, Andrea; Sbaragli, Tatiana; Comin, Antonella; Sylla, Lakamy; Monaci, Maurizio; Peric, Tanja; Stradaioli, Giuseppe

    2016-03-15

    Traditional superovulation protocols that include multiple gonadotropin treatments are time-consuming and labor intensive. These protocols require multiple handling and restraining of embryo donors. This will likely increase the risks of injuries in both animals and humans and induce stress that may lead to a reduced superovulatory response. These are more evident when working with cattle that are rarely handled or raised on extensive grazing. The objectives of this experiment were to compare the efficacy of a split-injection protocol of porcine pituitary-derived porcine FSH (pFSH) preparation (slow release [SR] group) to the traditional 4-day treatment with pFSH administered twice daily (C group) and to determine the concentrations of cortisol in the hair as a marker of activation of the hypothalamic-pituitary-adrenal (HPA) axis during the two superovulatory treatments. Thirty-two heifers were stimulated twice in a 2 × 2 crossover design and compared for ovarian response and numbers and characteristics of recovered ova-embryo among treatments. No differences between SR and C groups were found in terms of percentage of responsive animals (100% vs. 93.8%) and ovulation rate (83.7 ± 1.1 vs. 79.5 ± 1.0%). A positive correlation was found between the number of follicles responsive to pFSH (2-8 mm) at the beginning of treatments and the superovulatory response, and no differences were found in these follicular populations between the two treatment groups. The numbers of CLs, ova-embryos, fertilized ova, transferable and freezable embryos recovered per cow were found to be significantly higher in SR compared with C group (14.0 ± 1.6 vs. 10.6 ± 1.0, 12.1 ± 1.6 vs. 7.6 ± 1.0, 11.1 ± 1.1 vs. 7.3 ± 1.0, 9.6 ± 1.4 vs. 6.6 ± 1.0, and 9.4 ± 1.4 vs. 6.0 ± 1.0 for SR and C group, respectively). The SR group produced also a significantly greater number of excellent- and/or good-quality embryos compared with the C group. The concentrations of cortisol in the hair at

  12. Maus-tratos na infância e psicopatologia no adulto: caminhos para a disfunção do eixo hipotálamo-pituitária-adrenal Childhood maltreatment and adult psychopathology: pathways to hypothalamic-pituitary-adrenal axis dysfunction

    Directory of Open Access Journals (Sweden)

    Marcelo F. Mello

    2009-10-01

    psychopathology, as reflected in hypothalamic-pituitary-adrenal axis dysfunction. METHOD: A selective review of the relevant literature was undertaken in order to identify key and illustrative research findings. RESULTS: There is now a substantial body of preclinical and clinical evidence derived from a variety of experimental paradigms showing how early-life stress is related to hypothalamic-pituitary-adrenal axis function and psychological state in adulthood, and how that relationship can be modulated by other factors. DISCUSSION: The risk for adult psychopathology and hypothalamic-pituitary-adrenal axis dysfunction is related to a complex interaction among multiple experiential factors, as well as to susceptibility genes that interact with those factors. Although acute hypothalamic-pituitary-adrenal axis responses to stress are generally adaptive, excessive responses can lead to deleterious effects. Early-life stress alters hypothalamic-pituitary-adrenal axis function and behavior, but the pattern of hypothalamic-pituitary-adrenal dysfunction and psychological outcome in adulthood reflect both the characteristics of the stressor and other modifying factors. CONCLUSION: Research to date has identified multiple determinants of the hypothalamic-pituitary-adrenal axis dysfunction seen in adults with a history of childhood maltreatment or other early-life stress. Further work is needed to establish whether hypothalamic-pituitary-adrenal axis abnormalities in this context can be used to develop risk endophenotypes for psychiatric and physical illnesses.

  13. Temperament and hypothalamic-pituitary-adrenal axis function are related and combine to affect growth, efficiency, carcass, and meat quality traits in Brahman steers.

    Science.gov (United States)

    Cafe, L M; Robinson, D L; Ferguson, D M; Geesink, G H; Greenwood, P L

    2011-05-01

    analysis separated these traits into separate components, which in turn had different relations with productivity traits. The largest component of temperament was described similarly by FS and CS, but there were smaller components that these described differently. There were some temperament-related differences in the metabolic status of the steers which were not related to the variation in cortisol, suggesting involvement of the sympatho-adrenal-medullary axis in these temperament-related effects.

  14. Hair-Normalized Cortisol Waking Response as a Novel Biomarker of Hypothalamic-Pituitary-Adrenal Axis Activity following Acute Trauma: A Proof-of-Concept Study with Pilot Results

    Directory of Open Access Journals (Sweden)

    David M. Walton

    2013-01-01

    Full Text Available The mechanisms underlying the development of persistent posttraumatic pain and disability remain elusive. Recent evidence suggests that disordered stress-system pathway (hypothalamic-pituitary-adrenal axis activity may be responsible for the genesis and maintenance of long-term sensory and emotional problems. However, confidence in current evidence is limited by the necessarily retrospective collection of data. Hair cortisol can serve as a calendar of HPA axis activity going back several months prior to injury. The purposes of this pilot study were to determine the feasibility of using hair cortisol and hair-normalized salivary cortisol as biomarkers of distress following traumatic injuries of whiplash or distal radius fracture. Ten subjects provided complete data within 3 weeks of injury. Hair cortisol, cortisol waking response (CWR, and mean daily cortisol (MDC were captured at inception, as were self-report indicators of pain, disability, and pain catastrophizing. Pain and disability were also captured 3 months after injury. Results indicate that cortisol waking response may be a useful biomarker of current distress as measured using the pain catastrophizing scale, especially when normalized to 3-month hair cortisol (r=0.77 raw, 0.93 normalized. Hair-normalized CWR may also have predictive capacity, correlating with 3-month self-reported disability at r=0.70. While promising, the results must be viewed in light of the small sample.

  15. Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

    NARCIS (Netherlands)

    Meerlo, P; Koehl, M; van der Borght, K; Turek, FW

    2002-01-01

    Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine

  16. Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

    NARCIS (Netherlands)

    Meerlo, P; Koehl, M; van der Borght, K; Turek, FW

    2002-01-01

    Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine st

  17. Enhancement of BDNF Concentration and Restoration of the Hypothalamic-Pituitary-Adrenal Axis Accompany Reduced Depressive-Like Behaviour in Stressed Ovariectomised Rats Treated with Either Tualang Honey or Estrogen

    Directory of Open Access Journals (Sweden)

    Badriya Al-Rahbi

    2014-01-01

    Full Text Available A possible interaction between glucocorticoids and estrogen-induced increases in brain-derived-neurotrophic factor (BDNF expression in enhancing depressive-like behaviour has been documented. Here we evaluated the effects of Tualang honey, a phytoestrogen, and 17β-estradiol (E2 on the depressive-like behaviour, stress hormones, and BDNF concentration in stressed ovariectomised (OVX rats. The animals were divided into six groups: (i nonstressed sham-operated control, (ii stressed sham-operated control, (iii nonstressed OVX, (iv stressed OVX, (v stressed OVX treated with E2 (20 μg daily, sc, and (vi stressed OVX treated with Tualang honey (0.2 g/kg body weight daily, orally. Two months after surgery, the animals were subjected to social instability stress procedure followed by forced swimming test. Struggling time, immobility time, and swimming time were scored. Serum adrenocorticotropic hormone (ACTH and corticosterone levels, and the BDNF concentration were determined using commercially available ELISA kits. Stressed OVX rats displayed increased depressive-like behaviour with significantly increased serum ACTH and corticosterone levels, while the BDNF concentration was significantly decreased compared to other experimental groups. These changes were notably reversed by both E2 and Tualang honey. In conclusion, both Tualang honey and E2 mediate antidepressive-like effects in stressed OVX rats, possibly acting via restoration of hypothalamic-pituitary-adrenal axis and enhancement of the BDNF concentration.

  18. Hypothalamo-pituitary and immune-dependent adrenal regulation during systemic inflammation.

    Science.gov (United States)

    Kanczkowski, Waldemar; Alexaki, Vasileia-Ismini; Tran, Nguyen; Großklaus, Sylvia; Zacharowski, Kai; Martinez, Antoine; Popovics, Petra; Block, Norman L; Chavakis, Triantafyllos; Schally, Andrew V; Bornstein, Stefan R

    2013-09-03

    Inflammation-related dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is central to the course of systemic inflammatory response syndrome or sepsis. The underlying mechanisms, however, are not well understood. Initial activation of adrenocortical hormone production during early sepsis depends on the stimulation of hypothalamus and pituitary mediated by cytokines; in late sepsis, there is a shift from neuroendocrine to local immune-adrenal regulation of glucocorticoid production. Therefore, the modulation of the local immune-adrenal cross talk, and not of the neuroendocrine circuits involved in adrenocorticotropic hormone production, may be more promising in the prevention of the adrenal insufficiency associated with prolonged sepsis. In the present work, we investigated the function of the crucial Toll-like receptor (TLR) adaptor protein myeloid differentiation factor 88 (MyD88) in systemic and local activation of adrenal gland inflammation and glucocorticoid production mediated by lipopolysachharides (LPSs). To this end, we used mice with a conditional MyD88 allele. These mice either were interbred with Mx1 Cre mice, resulting in systemic MyD88 deletion, predominantly in the liver and hematopoietic system, or were crossed with Akr1b7 Cre transgenic mice, resulting thereby in deletion of MyD88, which was adrenocortical-specific. Although reduced adrenal inflammation and HPA-axis activation mediated by LPS were found in Mx1(Cre+)-MyD88(fl/fl) mice, adrenocortical-specific MyD88 deletion did not alter the adrenal inflammation or HPA-axis activity under systemic inflammatory response syndrome conditions. Thus, our data suggest an important role of immune cell rather than adrenocortical MyD88 for adrenal inflammation and HPA-axis activation mediated by LPS.

  19. Modeling of the hypothalamic-pituitary-adrenal axis-mediated interaction between the serotonin regulation pathway and the stress response using a Boolean approximation: a novel study of depression

    Science.gov (United States)

    2013-01-01

    Major depressive disorder (MDD) is a multifactorial disorder known to be influenced by both genetic and environmental factors. MDD presents a heritability of 37%, and a genetic contribution has also been observed in studies of family members of individuals with MDD that imply that the probability of suffering the disorder is approximately three times higher if a first-degree family member is affected. Childhood maltreatment and stressful life events (SLEs) have been established as critical environmental factors that profoundly influence the onset of MDD. The serotonin pathway has been a strong candidate for genetic studies, but it only explains a small proportion of the heritability of the disorder, which implies the involvement of other pathways. The serotonin (5-HT) pathway interacts with the stress response pathway in a manner mediated by the hypothalamic-pituitary-adrenal (HPA) axis. To analyze the interaction between the pathways, we propose the use of a synchronous Boolean network (SBN) approximation. The principal aim of this work was to model the interaction between these pathways, taking into consideration the presence of selective serotonin reuptake inhibitors (SSRIs), in order to observe how the pathways interact and to examine if the system is stable. Additionally, we wanted to study which genes or metabolites have the greatest impact on model stability when knocked out in silico. We observed that the biological model generated predicts steady states (attractors) for each of the different runs performed, thereby proving that the system is stable. These attractors changed in shape, especially when anti-depressive drugs were also included in the simulation. This work also predicted that the genes with the greatest impact on model stability were those involved in the neurotrophin pathway, such as CREB, BDNF (which has been associated with major depressive disorder in a variety of studies) and TRkB, followed by genes and metabolites related to 5-HT

  20. The role of sleep and the hypothalamic-pituitary-adrenal axis for behavioral and emotional problems in very preterm children during middle childhood.

    Science.gov (United States)

    Perkinson-Gloor, Nadine; Hagmann-von Arx, Priska; Brand, Serge; Holsboer-Trachsler, Edith; Grob, Alexander; Weber, Peter; Lemola, Sakari

    2015-01-01

    Very preterm children are at higher risk to develop behavioral and emotional problems, poor sleep, and altered hypothalamic-pituitary-adrenocortical activity (HPAA). However, knowledge on objective sleep and HPAA as well as their role for the development of behavioral and emotional problems in very preterm children is limited. Fifty-eight very preterm children (HPAA was assessed with four saliva samples in the morning (morning cortisol secretion) and four saliva samples in the evening (evening cortisol secretion). Parents completed the Strengths and Difficulties Questionnaire (SDQ) to assess children's behavioral and emotional problems and a subscale of the Children's Sleep Habits Questionnaire to assess sleep disordered breathing. Very preterm children showed more behavioral and emotional problems (SDQ total behavioral/emotional difficulties, emotional symptoms), poorer sleep (more nocturnal awakenings, more stage 2 sleep, less slow wave sleep), and faster decreasing evening cortisol secretion compared to full-term children. Across the whole sample, more stage 2 sleep and/or less slow wave sleep were associated with more SDQ total behavioral/emotional difficulties, hyperactivity-inattention, and peer problems. Lower morning cortisol secretion and lower evening cortisol secretion were associated with more conduct problems. In very preterm children, increased SDQ total behavioral/emotional difficulties was partially explained by less restorative sleep including more stage 2 sleep and less slow wave sleep. This result points to the importance of restorative sleep for the behavioral and emotional development of very preterm children during middle childhood. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Hypothalamic-pituitary-adrenal-axis dysregulation and double product increases potentiate ischemic heart disease risk in a Black male cohort: the SABPA study.

    Science.gov (United States)

    Malan, Leoné; Schutte, Christiaan E; Alkerwi, Ala'a; Stranges, Saverio; Malan, Nicolaas T

    2017-06-01

    Emotional distress has been associated with a poorer prognosis in myocardial infarction patients. Elevated adrenocorticotrophic hormone (ACTH), lower cortisol, dehydroepiandrosterone sulfate (DHEAS) and cortisol:DHEAS, as measures of emotional distress, might correlate with silent myocardial ischemia (SMI) and workload. Thus, we assessed the relationship between emotional distress, SMI and double product (systolic blood pressure (SBP) × heart rate). Cross-sectional South African biethnic single-set cohorts (N=378), aged 44.7±9.52 years, were investigated. Depressive symptoms (Patient Health Questionnaire-9), anthropometric, fasting blood, 24-h double product and 24-h 2-lead electrocardiogram (ST-segment depression) values were obtained. Blacks, mostly men, had increased depressive symptoms, hyperglycemia, SMI, double product, SBP hypertension and ACTH but lower cortisol, DHEAS and cortisol:DHEAS than their White counterparts. Black men had the highest combined SBP hypertension and below-median cortisol prevalence, 38%, compared with 5.9-13.8% in the other groups. Their SMI was associated with ACTH and cortisol:DHEAS (adj. R(2) 0.29; β 0.27-0.31 (0.12-0.64); P⩽0.05), double product (adj. R(2) 0.29; β 0.38 (0.18-0.57); P=0.050) and SBP hypertension (area under the curve: 0.68 (95% CI: 0.56, 0.80); P=0.042; sensitivity/specificity 49/85%). Double product was positively associated with central obesity in all sex groups and with cortisol in the Black men (PHPAA) showed signs of a hyporesponsive adrenal cortex, suggesting chronic emotional stress in the Black male cohort. In this cohort, HPAA dysregulation and compensatory increases in double product occur as a potential defense mechanism to alleviate perfusion deficits, thereby potentiating ischemic heart disease risk.

  2. Os efeitos do estresse na função do eixo hipotalâmico-pituitário-adrenal em indivíduos com esquizofrenia The effects of stress on hypothalamic-pituitary-adrenal (HPA axis function in subjects with schizophrenia

    Directory of Open Access Journals (Sweden)

    Francesca L. Guest

    2012-01-01

    Full Text Available Nas últimas décadas, têm surgido evidências sugerindo que a patogênese de desordens psiquiátricas, tais como a esquizofrenia, pode envolver perturbações no eixo hipotalâmico-pituitário-adrenal (HPA. Variações na manifestação desses efeitos poderiam estar relacionadas a diferenças em sintomas clínicos entre os indivíduos afetados, assim como a diferenças na resposta ao tratamento. Tais efeitos podem também ser originados de complexas interações entre genes e fatores ambientais. Aqui, revisamos os efeitos do estresse maternal em anormalidades na regulação do eixo HPA e desenvolvimento de desordens psiquiátricas, incluindo a esquizofrenia. Estudos nessa área podem gerar o aumento do nosso entendimento da natureza multidimensional da esquizofrenia. Posterior pesquisa nesse campo poderia, em última instância, levar ao desenvolvimento de melhores diagnósticos e novas abordagens terapêuticas para essa debilitante condição psiquiátrica.Over the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA axis. Variations in the manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response. Such effects can also arise from the complex interaction between genes and environmental factors. Here, we review the effects of maternal stress on abnormalities in HPA axis regulation and the development of psychiatric disorders including schizophrenia. Studies in this area may prove critical for increasing our understanding of the multi-dimensional nature of schizophrenia. Further research in this area could ultimately lead to the development of improved diagnostics and novel therapeutic approaches for treating this debilitating psychiatric condition.

  3. Os efeitos do estresse na função do eixo hipotalâmico-pituitário-adrenal em indivíduos com esquizofrenia The effects of stress on hypothalamic-pituitary-adrenal (HPA axis function in subjects with schizophrenia

    Directory of Open Access Journals (Sweden)

    Francesca L. Guest

    2013-01-01

    Full Text Available Nas últimas décadas, têm surgido evidências sugerindo que a patogênese de desordens psiquiátricas, tais como a esquizofrenia, pode envolver perturbações no eixo hipotalâmico-pituitário-adrenal (HPA. Variações na manifestação desses efeitos poderiam estar relacionadas a diferenças em sintomas clínicos entre os indivíduos afetados, assim como a diferenças na resposta ao tratamento. Tais efeitos podem também ser originados de complexas interações entre genes e fatores ambientais. Aqui, revisamos os efeitos do estresse maternal em anormalidades na regulação do eixo HPA e desenvolvimento de desordens psiquiátricas, incluindo a esquizofrenia. Estudos nessa área podem gerar o aumento do nosso entendimento da natureza multidimensional da esquizofrenia. Posterior pesquisa nesse campo poderia, em última instância, levar ao desenvolvimento de melhores diagnósticos e novas abordagens terapêuticas para essa debilitante condição psiquiátrica.Over the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA axis. Variations in the manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response. Such effects can also arise from the complex interaction between genes and environmental factors. Here, we review the effects of maternal stress on abnormalities in HPA axis regulation and the development of psychiatric disorders including schizophrenia. Studies in this area may prove critical for increasing our understanding of the multi-dimensional nature of schizophrenia. Further research in this area could ultimately lead to the development of improved diagnostics and novel therapeutic approaches for treating this debilitating psychiatric condition.

  4. 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.

  5. A soy-based phosphatidylserine/ phosphatidic acid complex (PAS) normalizes the stress reactivity of hypothalamus-pituitary-adrenal-axis in chronically stressed male subjects: a randomized, placebo-controlled study.

    Science.gov (United States)

    Hellhammer, Juliane; Vogt, Dominic; Franz, Nadin; Freitas, Ulla; Rutenberg, David

    2014-07-31

    Supplementation with a phosphatidylserine and phosphatidylserine/ phosphatidic acid complex (PAS) has been observed to normalize stress induced dysregulations of the hypothalamus-pituitary-adrenal axis (HPAA). Prolonged stress first induces a hyper-activation of the HPAA, which then can be followed by a state of hypo-activation.The aim of this study was to examine effects of an oral supplementation with 400 mg PS & 400 mg PA (PAS 400) per day on the endocrine stress response (ACTH, saliva and serum cortisol) to a psychosocial stressor. A special focus was to analyze subgroups of low versus high chronically stressed subjects as well as to test efficacy of 200 mg PS & 200 mg PA (PAS 200). 75 healthy male volunteers were enrolled for this double-blind, placebo-controlled study, stratified by chronic stress level, and randomly allocated to one of three study arms (placebo, PAS 200 and PAS 400 per day, respectively). Study supplementation was administered for 42 days for each participant. Chronic stress was measured with the Trier Inventory for Chronic Stress (TICS), and subgroups of high and low chronic stress were differentiated by median values as provided by the TICS authors. A six week period of supplementation was followed by an acute stress test (Trier Social Stress Test - TSST). Chronic stress levels and other baseline measures did not differ between treatment groups (all p>0.05). Acute stress was successfully induced by the TSST and resulted in a hyper-responsivity of the HPAA in chronically stressed subjects. Compared to placebo, a supplementation with a daily dose of PAS 400 was effective in normalizing the ACTH (p=0.010), salivary (p=0.043) and serum cortisol responses (p=0.035) to the TSST in chronically high but not in low stressed subjects (all p>0.05). Compared to placebo, supplementation with PAS 200 did not result in any significant differences in these variables (all p>0.05). There were no significant effects of supplementation with PAS on heart rate

  6. The research progress of obstructive sleep apnea-hypopnea syndrome and hypothalamic-pituitary-adrenal axis%阻塞性睡眠呼吸暂停低通气综合征与下丘脑-垂体-肾上腺轴关系研究进展

    Institute of Scientific and Technical Information of China (English)

    李兰凤; 余勤

    2015-01-01

    OSAHS is a serious,prevalent sleep breathing disorder that has signiflcantly high morbidity and mortality when untreated.OSAHS has been shown to be an independent risk factor of serious systemic diseases,such as hypertension,ischemic heart disease,cerebral vascular disease, congestive heart failure and arrhythmias.Many factors could regulate OSAHS in pathogenesis mechanism.Recent researches suggest that the disrupted hypothalamic-pituitary-adrenal (HPA)axis activity plays a great role in OSAHS.In this article,we will review the abnormal HPA axis and its possible mechanisms in patients with OSAHS.%OSAHS 是一种累及多系统并造成多器官损害的睡眠呼吸障碍性疾病,是高血压、心律失常及心、脑血管等多种严重疾病的独立危险因素。OSAHS 是多因素作用的结果,而近年来研究证实下丘脑-垂体-肾上腺(hypothalamic pituitary adrenal,HPA)轴的功能变化与 OSAHS 发病之间存在密切关系。现就 OSAHS 患者 HPA 轴功能变化及可能的相关机制作一综述。

  7. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

    Science.gov (United States)

    Oyola, Mario G; Handa, Robert J

    2017-08-31

    Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

  8. Chronic Stress and Limbic-Hypothalamopituitary-Adrenal Axis (LHPA Response in Female Reproductive system

    Directory of Open Access Journals (Sweden)

    Farideh Zafari Zangeneh

    2009-12-01

    Full Text Available The hypothalamo-pituitary-adrenocortical (HPA axis is a critical adaptive system that maximizes survival potential in the face of physical or psychological challenge. The principal end products of the HPA axis, glucocorticoid hormones, act on multiple organ systems, including the brain, to maintain homeostatic balance. The brain is a target of stress, and the hippocampus is the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. These anatomical areas in brain are limbic system, and in particular the hippocampus, medial prefrontal cortex (mPFC and amigdal that have multiple control points in regulation of the hypothalamic–pituitary–adrenal (HPA axis. The studies show the prefrontal cortex (PFC plays an important role in the regulation of stress-induced hypothalamic–pituitary–adrenal (HPA activity and regulation of gonadal function in men and women is under the control of the HPA. This regulation is complex and sex steroids are important regulators of GnRH and gonadotropin release through classic feedback mechanisms in the hypothalamus and pituitary gland. Chronic stress can have a deleterious effect on the reproductive axis that, for females, is manifested in reduced pulsatile gonadotropin secretion and increased incidence of ovulatory abnormalities and infertility. The limbic–hypothalamic–pituitary–adrenal (LHPA axis suggests a functional role for gonadal steroids in the regulation of a female’s response to stress.

  9. Chronic stress and pituitary-adrenal function in female pigs

    NARCIS (Netherlands)

    Janssens, C.J.J.G.

    1994-01-01

    Introduction

    The main purpose of the studies described in this thesis was to gain more insight in the regulation of the hypothalamic-pituitary-adrenocorticaI (HPA) system and the mechanisms underlying adaptation to chronic stress in female pigs. The function of the HPA axis, which

  10. Chronic stress and pituitary-adrenal function in female pigs.

    NARCIS (Netherlands)

    Janssens, C.J.J.C.

    1994-01-01

    IntroductionThe main purpose of the studies described in this thesis was to gain more insight in the regulation of the hypothalamic-pituitary-adrenocorticaI (HPA) system and the mechanisms underlying adaptation to chronic stress in female pigs. The function of the HPA axis, which coordinates multipl

  11. Chronic stress and pituitary-adrenal function in female pigs

    NARCIS (Netherlands)

    Janssens, C.J.J.G.

    1994-01-01

    Introduction

    The main purpose of the studies described in this thesis was to gain more insight in the regulation of the hypothalamic-pituitary-adrenocorticaI (HPA) system and the mechanisms underlying adaptation to chronic stress in female pigs. The function of the HPA axis, which coordinate

  12. 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.

  13. The Nutrient and Energy Sensor Sirt1 Regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis by Altering the Production of the Prohormone Convertase 2 (PC2) Essential in the Maturation of Corticotropin-releasing Hormone (CRH) from Its Prohormone in Male Rats.

    Science.gov (United States)

    Toorie, Anika M; Cyr, Nicole E; Steger, Jennifer S; Beckman, Ross; Farah, George; Nillni, Eduardo A

    2016-03-11

    Understanding the role of hypothalamic neuropeptides and hormones in energy balance is paramount in the search for approaches to mitigate the obese state. Increased hypothalamic-pituitary-adrenal axis activity leads to increased levels of glucocorticoids (GC) that are known to regulate body weight. The axis initiates the production and release of corticotropin-releasing hormone (CRH) from the paraventricular nucleus (PVN) of the hypothalamus. Levels of active CRH peptide are dependent on the processing of its precursor pro-CRH by the action of two members of the family of prohormone convertases 1 and 2 (PC1 and PC2). Here, we propose that the nutrient sensor sirtuin 1 (Sirt1) regulates the production of CRH post-translationally by affecting PC2. Data suggest that Sirt1 may alter the preproPC2 gene directly or via deacetylation of the transcription factor Forkhead box protein O1 (FoxO1). Data also suggest that Sirt1 may alter PC2 via a post-translational mechanism. Our results show that Sirt1 levels in the PVN increase in rats fed a high fat diet for 12 weeks. Furthermore, elevated Sirt1 increased PC2 levels, which in turn increased the production of active CRH and GC. Collectively, this study provides the first evidence supporting the hypothesis that PVN Sirt1 activates the hypothalamic-pituitary-adrenal axis and basal GC levels by enhancing the production of CRH through an increase in the biosynthesis of PC2, which is essential in the maturation of CRH from its prohormone, pro-CRH.

  14. 四逆汤对脓毒症患者下丘脑-垂体-肾上腺轴的影响%Effect of Sini decoction on function of hypothalamic-pituitary-adrenal axis in patients with sepsis

    Institute of Scientific and Technical Information of China (English)

    黄若兰; 张忠; 徐慕娟; 常晓; 乔秋杰; 王玲; 孟新科

    2014-01-01

    Objective To investigate the effects of Sini decoction on function of hypothalamic-pituitary-adrenal axis in patients with sepsis.Methods A prospective single-blind randomized controlled trial was conducted.60 septic patients were divided into three groups with the method of random number table,20 cases in the control group,20 in the Chinese herb group,and 20 in corticoid group.All of them received routine treatment.Patients in Chinese herb group were given Sini decoction in addition (decoction of monkshood 15 g,dried ginger 15 g,honey-fried licorice 10 g) 100 mL/d orally or by nasal feeding,while patients in corticoid group were given hydrocortisone 200 mg/d intravenously instead,both for 7 days.Before the treatment,3 days and 14 days after treatment,blood was collected to determine the levels of adrenocorticotropic hormone (ACTH) and cortisol,and the result of ACTH stimulating test was observed.At the same time,acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was recorded,and 3-day shock recovery rate and 28-day death rate were also compared among these groups.Results None of the three groups showed different result in ACTH stimulating test (x2=1.101,P=0.605).ACTH in three groups was gradually decreased.Compared with that before treatment,ACTH in Chinese herb group and corticoid groups began to decrease obviously on day 3 (ng/L:29.90 ± 3.31 vs.33.10 ±.3.31,28.20 ±.2.45 vs.33.30 ± 3.84,both P<0.01),while in control group declined ACTH appeared later (on day 14) compared with before treatment (ng/L:29.40 ±5.63 vs.33.50 ±4.89,P<0.05).No obvious difference in ACTH level was showed between the Chinese herb group and the cortical group (both P>0.05).Cortisol level in both Chinese herb and cortical groups showed a raise-fall biphase trend while there was no change in the control.The cortical levels on day 3 in Chinese herb and cortical groups were much higher than that before treatment (μg/L:343.04 ± 31.20 vs.294.70 ±42.10,331.25 ±42

  15. Mathematical modeling of the hypothalamic–pituitary–adrenal gland (HPA) axis, including hippocampal mechanisms

    DEFF Research Database (Denmark)

    Andersen, Morten; Vinther, Frank; Ottesen, Johnny T.

    2013-01-01

    non-negative and bounded, which can be interpreted as a mathematical formulation of homeostasis. No oscillating solutions are present when using physiologically reasonable parameter values. This indicates that the ultradian rhythm originate from different mechanisms.Using physiologically reasonable......This paper presents a mathematical model of the HPA axis. The HPA axis consists of the hypothalamus, the pituitary and the adrenal glands in which the three hormones CRH, ACTH and cortisol interact through receptor dynamics. Furthermore, it has been suggested that receptors in the hippocampus have...

  16. [Hypoplasia adrenal congenita of anencephalic type: two cases with pituitary abnormalities and review of literature].

    Science.gov (United States)

    Folligan, K; Roume, J; Razavi, F; Sepaniak, S; Bouvier, R; Morel, Y; Trouillas, J

    2011-03-01

    Hypoplasia adrenal congenita is an extremely uncommon disease of early onset. This condition can be lethal in the absence of treatment. Some forms are due to the congenital adrenal hypoplasia of anencephalic type whose origin is even unknown. Here, we present two cases of congenital adrenal hypoplasia of anencephalic type with pituitary abnormalities. The two male newborns died because adrenal insufficiency in the neonatal period. The adrenal glands were hypoplastic with a histological structure of anencephalic type Immunocytochemical study of the pituitary revealed an absence of the gonadotrophs. No mutation of DAX 1 and SF-1 was found.

  17. Functional cross-talk between the hypothalamic-pituitary-gonadal and -adrenal axes.

    Science.gov (United States)

    Viau, V

    2002-06-01

    Under normal conditions, the adrenal glucocorticoids, the endproduct of the hypothalamic-pituitary-adrenal (HPA) axis, provide a frontline of defence against threats to homeostasis (i.e. stress). On the other hand, chronic HPA drive and glucocorticoid hypersecretion have been implicated in the pathogenesis of several forms of systemic, neurodegenerative and affective disorders. The HPA axis is subject to gonadal influence, indicated by sex differences in basal and stress HPA function and neuropathologies associated with HPA dysfunction. Functional cross-talk between the gonadal and adrenal axes is due in large part to the interactive effects of sex steroids and glucocorticoids, explaining perhaps why several disease states linked to stress are sex-dependent. Realizing the interactive nature by which the hypothalamic-pituitary-gonadal and HPA systems operate, however, has made it difficult to model how these hormones act in the brain. Manipulation of one endocrine system is not without effects on the other. Simultaneous manipulation and assessment of both endocrine systems can overcome this problem. This dual approach in the male rat reveals that testosterone can act and interact on different aspects of basal and stress HPA function. Basal adrenocorticotropic hormone (ACTH) release is regulated by testosterone-dependent effects on arginine vasopressin synthesis, and corticosterone-dependent effects on corticotropin-releasing hormone (CRH) synthesis in the paraventricular nucleus (PVN) of the hypothalamus. In contrast, testosterone and corticosterone interact on stress-induced ACTH release and drive to the PVN motor neurones. Candidate structures mediating this interaction include several testosterone-sensitive afferents to the HPA axis, including the medial preoptic area, central and medial amygdala and bed nuclei of the stria terminalis. All of these relay homeostatic information and integrate reproductive and social behaviour. Because these modalities are affected

  18. Sympathetic and hypothalamic-pituitary-adrenal asymmetry in generalized anxiety disorder.

    Science.gov (United States)

    Reeves, Jonathan W; Fisher, Aaron J; Newman, Michelle G; Granger, Douglas A

    2016-06-01

    Physiologic investigations of generalized anxiety disorder (GAD) have skewed toward assessment of the autonomic nervous system, largely neglecting hypothalamic-pituitary-adrenal (HPA) axis variables. Although these systems coordinate-suggesting a degree of symmetry-to promote adaptive functioning, most studies opt to monitor either one system or the other. Using a ratio of salivary alpha-amylase (sAA) over salivary cortisol, the present study examined symmetry between the sympathetic nervous system (SNS) and HPA axis in individuals with GAD (n = 71) and healthy controls (n = 37). Compared to healthy controls, individuals with GAD exhibited greater baseline ratios of sAA/cortisol and smaller ratios of sAA/cortisol following a mental arithmetic challenge. We propose that the present study provides evidence for SNS-HPA asymmetry in GAD. Further, these results suggest that increased SNS suppression in GAD may be partially mediated by cortisol activity.

  19. MRI of the hypothalamic-pituitary axis in children

    Energy Technology Data Exchange (ETDEWEB)

    Argyropoulou, Maria I. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Kiortsis, Dimitrios Nikiforos [University of Ioannina, Department of Physiology, Medical School, Ioannina (Greece)

    2005-11-01

    In childhood, the MR characteristics of the normal pituitary gland are well established. During the first 2 months of life the adenohypophysis demonstrates high signal. Pituitary gland height (PGH) decreases during the 1st year of life and then increases, reaching a plateau after puberty. The magnetization transfer ratio (MTR) increases in both sexes up to the age of 20 years. On dynamic contrast-enhanced studies, the posterior pituitary lobe enhances simultaneously with the straight sinus, and the adenohypophysis later, but within 30 s. In genetically determined dysfunctional states, the adenohypophysis may be normal, hypoplastic, or enlarged. Pituitary enlargement, observed in Prop 1 gene mutations, is characterized by a mass interposed between the anterior and posterior lobes. An ectopic posterior lobe (EPP), associated with a hypoplastic or absent pituitary stalk, may be observed in patients with hypopituitarism. Tumors of the hypothalamic-pituitary (HP) axis may be the origin of adenohypophyseal deficiencies. A small hypointense adenohypophysis is found in iron overload states and is often associated with hypogonadotrophic hypogonadism. Absence of the posterior lobe bright signal, with or without a thick pituitary stalk or a mass at any site from the median eminence to the posterior pituitary lobe, may be found in diabetes insipidus. Hydrocephalus, suprasellar arachnoid cysts, hypothalamic hamartomas and craniopharyngiomas may result in central precocious puberty (CPP). Increased PGH in girls with idiopathic CPP is useful for its differential diagnosis from premature thelarche (PT). Pituitary adenomas, observed mainly in adolescents, present the same MR characteristics as those in adults. (orig.)

  20. 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.

  1. THE ASSESSMENT OF THE FUNCTIONAL-CAPACITY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS BY MEASUREMENT OF BASAL PLASMA AND URINARY CORTISOL IN COMPARISON WITH INSULIN-INDUCED HYPOGLYCEMIA AND METYRAPONE TESTS

    NARCIS (Netherlands)

    DELANGE, WE; SLUITER, WJ

    1993-01-01

    In 58 patients with a pituitary adenoma or hypothalamic-pituitary disease an insulin-induced hypoglycaemia test and a metyrapone test were performed. The results of these tests were compared with morning plasma cortisol levels and daily urinary cortisol excretion as indicators of insufficiency of th

  2. Pituitary-adrenal response in preterm very low birth weight infants after treatment with antenatal corticosteroids

    National Research Council Canada - National Science Library

    Ng, P C; Wong, G W; Lam, C W; Lee, C H; Wong, M Y; Fok, T F; Wong, W; Chan, D C

    1997-01-01

    Antenatal corticosteroids have been widely used for the prevention of respiratory distress syndrome in preterm neonates, yet little is known about their effects on the hypothalamic-pituitary-adrenal...

  3. Fisiopatología de la disfunción gonadal en la Amenorrea Hipotalámica funcional (AHF y su relación con la activación del eje hipotálamo-hipófiso-adrenal Pathophysiology of gonadal dysfunction in functional Hypothalamic Amenorrhea (FHA and its relation to activation of the hypothalamic-pituitary-adrenal axis

    Directory of Open Access Journals (Sweden)

    León Fiszlejder

    2011-06-01

    adiponectin, among other adipocytokines, and ghrelin, synthesized in the upper gastrointestinal tract. Fat mass reduction in these undernourished women and the resulting decrease in leptin leads to neuropeptide Y (NPY synthesis in the hypothalamus. This peptide, through direct or indirect action mediated by CRH stimulation, and the activation of the opioid and dopaminergic system block the receptors of the GnRH-synthesizing neurons in the arcuate nucleus to inhibit, and thus disturb, the gonadotropin pulsatile activity. The increase in ghrelin also blocks this activity through a complex mechanism: NPY synthesis is stimulated and NPY, in turn, inhibits GABA interneurons, thus altering the suppressant action normally exerted by this neurotransmitter on the CRH. The increase in serotonin levels activates the limbic-hypothalamic-pituitary-adrenal system, probably indirectly, mediated by desensitization of glucocorticoid receptors of CRH immunoreactive neurons, thus inducing secretion. CRH concentrations in cerebrospinal fluid, as well as 24-h mean plasma cortisol concentrations are high, and their half-life is prolonged. Additionally, there is a decrease in CBG associated with elevated free urinary cortisol levels. Basal serum cortisol levels are not suppressed by the administration of dexamethasone and the ACTH response to CRH stimulation is blunted. These findings suggest an alteration of cortisol negative feedback effects on CRH-ACTH secretion. The mechanisms of this resistance to cortisol are not fully elucidated. Animal studies suggest that prolonged stress modifies the density and ratio of gluco- and mineralocorticoid receptors and post-receptor activity. By extrapolation, it could be inferred that this resistance to cortisol in patients with amenorrhea is a mechanism that tends to perpetuate adrenal axis hyperactivity. In addition, the activation of the sympathetic system with the increase in norepinephrine and epinephrine and its association with other factors produces an

  4. Hair cortisol levels as a retrospective marker of hypothalamic-pituitary axis activity throughout pregnancy: Comparison to salivary cortisol

    OpenAIRE

    D’Anna-Hernandez, Kimberly L.; ROSS, RANDAL G .; Natvig, Crystal L.; Laudenslager, Mark L.

    2011-01-01

    Maternal stress during pregnancy is associated with negative maternal/child outcomes. One potential biomarker of the maternal stress response is cortisol, a product of activity of the hypothalamic-pituitary-adrenal axis. This study evaluated cortisol levels in hair throughout pregnancy as a marker of total cortisol release. Cortisol levels in hair have been shown to be easily quantifiable and may be representative of total cortisol release more than single saliva or serum measures. Hair corti...

  5. O eixo hipotálamo-pituitária-adrenal, a função dos receptores de glicocorticóides e sua importância na depressão The Hypothalamic Pituitary Adrenal axis, Glucocorticoid receptor function and relevance to depression

    Directory of Open Access Journals (Sweden)

    Mario F Juruena

    2004-09-01

    abordagem eficaz para maximizar os efeitos terapêuticos dos antidepressivos. Hipóteses referentes aos mecanismos destes receptores envolvem compostos não esteróides que regulam a função dos RGs via segundos mensageiros. A pesquisa nesta área trará novos entendimentos à fisiopatologia e ao tratamento dos transtornos afetivos, em especial na depressão.OBJECTIVES: Changes in the hypothalamic-pituitary-adrenocortical (HPA system are characteristic of depression. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR, several studies have examined the number and/or function of GRs in depressed patients. METHODS: Review scientific evidences have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of CRF in various brain regions postulated to be involved in the causality of depression. RESULTS: This article summarizes the literature on GR in depression and on the impact of antidepressants on the GR in clinical and preclinical studies, and supports the concept that impaired GR signalling is a key mechanism in the pathogenesis of depression, in the absence of clear evidence of decreased GR expression. The data also indicate that antidepressants have direct effects on the GR, leading to enhanced GR function and increased GR expression. Although the effects of antidepressants on glucocorticoid hormones and their receptors are relevant for the therapeutic action of these drugs, the molecular mechanisms underlying these effects are unclear. We propose that antidepressants in humans could inhibit steroid transporters localised on the blood-brain barrier and in neurones, like the multidrug resistance p-glycoprotein, and thus increase the access of cortisol to the brain and the glucocorticoid-mediated negative feedback on the HPA axis. CONCLUSION: Enhanced cortisol action

  6. 脂多糖刺激对断奶仔猪下丘脑-垂体-肾上腺轴PPARγ表达的影响%Effects of Lipopolysaccharide Challenge on PPARγ Expression in Hypothalamus Pituitary Gland Adrenal Gland Axis of Weanling Pigs

    Institute of Scientific and Technical Information of China (English)

    刘玉兰; 石君霞; 鲁晶; 古殿超; 朱惠玲; 侯永清; 丁斌鹰

    2011-01-01

    The experiment was conducted to investigate the effects of lipopolysaccharide(LPS) on peroxisome proliferator-activated receptor-y (PPARy) expression in the hypothalamus pituitary gland adrenal gland(HPA) axis of weanling pigs. The pigs in the treatment group were injected intraperitoneally with LPS, whereas pigs in the control group were injected with sterile saline. Blood samples were collected at 1.5 and 3 h post-challenge. Following blood collection at 3 h, the pigs were slaughtered. The results showed that, at 1.5 h, LPS reduced neutrophil number and proportion (P < 0.05). At 3 h, LPS reduced white blood cell, lymphocyte and neutrophil (P < 0.05). Tumour necrosis factor-α and cortisol were increased significantly 1.5 and 3 h after LPS challenge (P < 0.01), adrenal cortical hormone was increased significantly 1.5 h after LPS challenge (P < 0.05), and adrenocorticotropic hormone was increased significantly (P < 0.05) 3 h after LPS challenge. LPS challenge increased PPARγ-positive cell percentage in the hypothalamus, adenohypophysis, adrenal cortex and adrenal medulla (P < 0.05). These results indicate that LPS challenge induces acute immunological stress in Pigs, and actives HPA axis and induces PPARy expression of HPA axis.%研究脂多糖(LPS)对断奶仔猪下丘脑-垂体-肾上腺(HPA)轴过氧化物酶体增殖物活化受体γ(PPARγ)表达的影响.对照组注射生理盐水,试验组注射LPS.注射后1.5 h和3 h采血,3 h采血后屠宰.结果表明:LPS刺激后1.5 h,中性粒细胞含量及其比例显著下降(P<0.05);LPS刺激后3 h,白细胞、淋巴细胞、中性粒细胞含量显著下降(P<0.05).LPS刺激后1.5 h,血浆肿瘤坏死因子(TNF)-a、皮质醇和促肾上腺皮质激素释放素激素(CRH)含量显著上升(P<0.05);LPS刺激后3 h,血浆TNF-a、皮质醇和促肾上腺皮质激素(ACTH)含量显著上升(P<0.05);LPS刺激导致下丘脑、腺垂体、肾上腺皮质和髓质中PPARγ阳性细胞百分率显著升高(P<0.05).这

  7. Brain changes underlying the long-term effects of a single previous exposure to emotional or systemic stressors in rats a view from the hypothalamic-pituitary-adrenal axis /

    OpenAIRE

    Vallès i Sánchez, Astrid

    2003-01-01

    Descripció del recurs: el 31 d'octubre de 2003 Estímuls estressants bàsicament emocionals, com la immobilització en taula (IMO), exerceixen efectes a llarg termini sobre l'activitat de l'eix hipotalàmic-pituïtari-adrenal (HPA) en rates adultes. Aquests efectes es caracteritzen per una desensibilització, primer a nivell perifèric (d'adrenocorticotropina (ACTH) y de corticosterona al cap d'uns dies) i més tard a nivell central (d'mRNA de corticoliberina (CRF) en el nucli paraventricular de l...

  8. Pituitary Adenoma as a Rare Form of Secondary Adrenal Insufficiency. A Case Report

    Directory of Open Access Journals (Sweden)

    Ana María León Blasco

    2014-02-01

    Full Text Available Pituitary adenomas are benign tumors arising from one of the five cell types in the anterior pituitary. Secondary adrenal insufficiency occurs when the adrenal glands do not produce hormones due to the lack of pituary adrenocorticotropic hormone or hypothalamic corticotropin-releasing factor. The case of a 37-year-old female patient who started developing muscle twitching in legs and arms, muscular weakness, fatigue, muscle aches, severe and throbbing hemicrania on the right side, among other symptoms, a year ago is presented. Several tests were performed (cortisol level, adrenocorticotropic hormone, calcium and phosphorus in blood and urine, magnetic resonance imaging of the skull, leading to the diagnosis of pituitary adenoma with isolated adrenocorticotropic hormone deficiency and secondary adrenal insufficiency. Treatment with steroids and calcium supplements ensured a satisfactory recovery.

  9. Crossover of the hypothalamic pituitary-adrenal/interrenal (HPA, -thyroid (HPT, and -gonadal (HPG axes in testicular development

    Directory of Open Access Journals (Sweden)

    Diana C. Castañeda Cortés

    2014-08-01

    Full Text Available Besides the well-known function of thyroid hormones (THs for regulating metabolism, it has recently been discovered that THs are also involved in testicular development in mammalian and non-mammalian species. THs, in combination with follicle stimulating hormone (FSH, lead to androgen synthesis in Denio rerio, which results in the onset of spermatogenesis in the testis, potentially relating the hypothalamic-pituitary-thyroid gland (HPT to the hypothalamic-pituitary-gonadal (HPG axes. Furthermore, studies in non-mammalian species have suggested that by stimulating the thyroid-stimulating hormone (TSH, THs can be induced by corticotropin-releasing hormone (CRH. This suggests that the hypothalamic-pituitary-adrenal/interrenal gland (HPA axis might influence the HPT axis. Additionally, it was shown that hormones pertaining to both HPT and HPA could also influence the HPG endocrine axis. For example, high levels of androgens were observed in the testis in Odonthestes bonariensis during a period of stress-induced sex determination, which suggests that stress hormones influence the gonadal fate towards masculinization. Thus, this review highlights the hormonal interactions observed between the HPT, HPA and HPG axes using a comparative approach in order to better understand how these endocrine systems could interact with each other to influence the development of testes.

  10. 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

  11. The expression and significance of IL -6/STAT3 signaling pathway on the hypothalamus -pituitary-adrenal axis in the early stage of sepsis rats%IL -6/STAT3信号通路在脓毒症早期大鼠下丘脑-垂体-肾上腺轴中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    王晓丹; 聂文龙; 张玉想

    2015-01-01

    Objective To explore the inner link between interleukin -6 ( IL -6 )/signal transducer and activator of transcription 3 ( STAT3 ) signaling pathway and hypothalamus -pituitary -adrenal axis ( HPAA) excessive activation in the early stage of sepsis rats .Methods Twenty -four adult male Wistar rats were randomly divided into Control group ( n=8 ) , sham-operated group ( n=8) and CLP group (n=8).The septic rat models were challenged by CLP , executed after 6 hours, the hypothalamus, pituitary and adrenal gland was isolated .Expression levels of CRH, IL-6, STAT3 and SOCS3 mRNA in hypothalamus , POMC, IL-6, STAT3 and SOCS3 mRNA in pituitary and IL -6, STAT3 and SOCS3 mRNA in adrenal gland were quantified by real -time quantitative PCR ( RT -PCR).Results Compared to Control group and Sham group: CRH, IL -6, STAT3 and SOCS3 mRNA expression levels were up -regulated significantly (P<0.01) in the hypothalamus tissues of CLP group;POMC, IL-6, STAT3 and SOCS3 mRNA expression levels were up -regulated significantly (P<0.01) in the pituitary tissues of CLP group; IL-6, STAT3 and SOCS3 mRNA expression levels were up-regulated significantly (P<0.01) in adrenal gland tissues of CLP group .Expression levels of all purpose gene were not different in Control group and Sham group .Conclusion IL -6/STAT3 signaling pathway has a close relationship with HPAA excessive activation in the early stage of sepsis rats.IL-6/STAT3 signaling pathway may be regarded as a novel therapeutic target for HPAA excessive activation of the sepsis .%目的:探讨大鼠脓毒症早期出现的HPA轴过度激活与IL-6/STAT3信号通路的内在联系。方法24只健康雄性Wistar大鼠,随机分为正常对照组( Control组)、假手术组( Sham组)、模型组(CLP组)三组。采用盲肠结扎穿孔(CLP)法建立脓毒症模型,术后6 h处死,分离出下丘脑、垂体、肾上腺组织。 RT-PCR检测下丘脑组织CRH、IL-6、STAT3、SOCS3 mRNA水平,垂体

  12. Effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill on hypothalamic-pituitary-adrenal axis negative feedback function in rat models of chronic stress-induced depression%慢性应激抑郁模型大鼠下丘脑-垂体-肾上腺轴负反馈功能与蒙药槟榔十三味丸的干预

    Institute of Scientific and Technical Information of China (English)

    包伍叶; 范盎然; 白亮凤; 佟海英; 于雪; 乌吉斯古冷; 李婧; 胡日乐巴根; 张月

    2014-01-01

    BACKGROUND:Mongolian Pharmaceutical Betel Shisanwei Ingredients Pil has achieved good clinical efficacy, but the underlying mechanism remains unclear. OBJECTIVE: To study the effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pil on the hypothalamic-pituitary-adrenal axis negative feedback function in the chronic depressed rats, and to explore anti-depression mechanisms of Mongolian Pharmaceutical Betel Shisanwei ingredients pil. METHODS: Eighty male Wistar rats were randomly divided into ten groups according to the sugar consumption test (with eight rats in each group): normal control group, model group, fluoxetine group, high-, medium- and low-dose Betel Shisanwei Ingredients Pil groups, RU486 group, high-, medium- and low-dose Betel Shisanwei Ingredients Pil plus RU486 groups. Except normal control group, the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely rising, to establish depression models. In the meantime, rats of the high-, medium- and low-dose Betel Shisanwei Ingredients Pil groups were given oral gavage of Betel Shisanwei Ingredients Pil (0.2, 0.4, 0.8 g/kg) for 28 days; rats of the normal control group and model group were intragstricaly administered with sodium carboxymethyl celulose; rats of RU486 group were given abdominal subcutaneous injection of RU486 from day 21 after modeling; rats of the high-, medium- and low-dose Betel Shisanwei Ingredients Pil plus RU486 groups were intragstricaly administered with Betel Shisanwei Ingredients Pil (0.2, 0.4, 0.8 g/kg) and subcutaneous injection of RU486 from day 21. RESULTS AND CONCLUSION:Compared with normal control group, cortisone content increased significantly (P < 0.05), the expression of glucocorticoid receptor mRNA in hippocampus, hypothalamus and pituitary gland decreased significantly, and hypothalamic corticotrophin releasing hormone mRNA expression increased significantly in the model group and RU486 group. Compared with model

  13. Research Progress in Interactions of the Circadian Clock System and the Hypothalamic-pituitary-adrenal Axis%生物钟系统与下丘脑-垂体-肾上腺轴相互作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    韩鹤(综述); 戴泽平(审校)

    2015-01-01

    Organisms have developed concurrent behavioral and physiological adaptations to the strong influence of day/night cycles, as well as to unforeseen, random stress stimuli.These circadian and stress-related responses are achieved by two highly conserved and interrelated regulatory networks,the circadian clock and stress systems, which respectively consist of oscillating molecular pacemakers,the Clock/Bmal1 transcription factors, and the hypothalamic-pituitary-adrenal axis and its end-effector, the glucocorticoid receptor.These systems communicate with each other at different signaling levels,and dysregulation of either system may lead to development of pathologic conditions.%在生物进化的早期,生物体已建立起对昼夜节律变化以及不可预见的随机应激刺激同时产生适应性行为和生理反应的能力,这些昼夜节律及应激相关的反应是通过两个高度保守且密切相关的调控网络-生物钟系统和应激系统来完成的,生物钟系统由震荡分子起搏器,Clock/Bmal1生物钟转录因子构成,应激系统由下丘脑-垂体-肾上腺轴及其末端效应物糖皮质激素受体构成。两者在不同的信号水平上相互联系,任意一个系统出现调节异常均会导致病理情况的发生发展。

  14. Antidepressant-Like Effects of Fractions Prepared from Danzhi-Xiaoyao-San Decoction in Rats with Chronic Unpredictable Mild Stress: Effects on Hypothalamic-Pituitary-Adrenal Axis, Arginine Vasopressin, and Neurotransmitters

    Directory of Open Access Journals (Sweden)

    Li-Li Wu

    2016-01-01

    Full Text Available The aim of the present study was to investigate the antidepressant-like effects of two fractions, including petroleum ether soluble fraction (Fraction A, FA and water-EtOH soluble fraction (Fraction B, FB prepared from the Danzhi-xiaoyao-san (DZXYS by using chronic unpredictable mild stress-induced depressive rat model. The results indicated that DZXYS could ameliorate the depression-like behavior in chronic stress model of rats. The inhibition of hyperactivity of HPA axis and the modulation of monoamine and amino acid neurotransmitters in the hippocampus may be the important mechanisms underlying the action of DZXYS antidepressant-like effect in chronically stressed rats.

  15. Effect of animal facility construction on basal hypothalamic-pituitary-adrenal and renin-aldosterone activity in the rat.

    Science.gov (United States)

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

    2011-04-01

    Although loud noise and intense vibration are known to alter the behavior and phenotype of laboratory animals, little is known about the effects of nearby construction. We studied the effect of a nearby construction project on the classic stress hormones ACTH, corticosterone, renin, and aldosterone in rats residing in a barrier animal facility before, for the first 3 months of a construction project, and at 1 month after all construction was completed. During some of the construction, noise and vibrations were not obvious to investigators inside the animal rooms. Body weight matched for age was not altered by nearby construction. During nearby construction, plasma ACTH, corticosterone, and aldosterone were approximately doubled compared with those of pre- and postconstruction levels. Expression of CRH mRNA in the paraventricular nucleus of the hypothalamus, CRH receptor and POMC mRNA in the anterior pituitary, and most mRNAs for steroidogenic genes in the adrenal gland were not significantly changed during construction. We conclude that nearby construction can cause a stress response without long-term effects on hypothalamic-pituitary-adrenal axis gene expression and body weight.

  16. Modeling the brain-pituitary-gonad axis in salmon

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jonghan; Hayton, William L.; Schultz, Irv R.

    2006-08-24

    To better understand the complexity of the brain-pituitary-gonad axis (BPG) in fish, we developed a biologically based pharmacodynamic model capable of accurately predicting the normal functioning of the BPG axis in salmon. This first-generation model consisted of a set of 13 equations whose formulation was guided by published values for plasma concentrations of pituitary- (FSH, LH) and ovary- (estradiol, 17a,20b-dihydroxy-4-pregnene-3-one) derived hormones measured in Coho salmon over an annual spawning period. In addition, the model incorporated pertinent features of previously published mammalian models and indirect response pharmacodynamic models. Model-based equations include a description of gonadotropin releasing hormone (GnRH) synthesis and release from the hypothalamus, which is controlled by environmental variables such as photoperiod and water temperature. GnRH stimulated the biosynthesis of mRNA for FSH and LH, which were also influenced by estradiol concentration in plasma. The level of estradiol in the plasma was regulated by the oocytes, which moved along a maturation progression. Estradiol was synthesized at a basal rate and as oocytes matured, stimulation of its biosynthesis occurred. The BPG model can be integrated with toxico-genomic, -proteomic data, allowing linkage between molecular based biomarkers and reproduction in fish.

  17. Brain-Pituitary Axis Development In The CEBAS Minimodule

    Science.gov (United States)

    Schreibman, Martin P.; Magliulo-Cepriano, Lucia

    2001-01-01

    The CEBAS minimodule system is a man-made aquatic ecological system that incorporates animals, plants, snails, and microorganisms. It has been proposed that CEBAS will lead to a multigenerational experimental facility for utilization in a space station as well as for the development of an aquatic CELSS to produce animal and plant biomass for human nutrition. In this context, research on the reproductive biology of the organisms within the system should receive the highest priority. 1bus, the goals of our proposal were to provide information on space-flight-induced changes in the brain-pituitary axis and in the organs that receive information from the environment in the vertebrate selected for the CEBAS Minimodule program, the freshwater teleost Xiphophorus helleri (the swordtail). We studied the development of the brain- pituitary axis in neonates, immature and mature swordtails using histology, cytology, immunohistochemistry, morphometry, and in situ histochemistry to evaluate the synthesis, storage, and release of neurotransmitters, neuroregulatory peptides, neurohormones, and pituitary hormones as well as the structure of the organs and cells that produce, store, or are the target organs for these substances. We flew experiments in the CEBAS-minimodule on two shuttle missions, STS-89 and STS-90. In both flights four gravid females and about 200 juvenile (7 days old) swordtails (Xiphophorus helleri) constituted the aquatic vertebrates to be studied, in addition to the plants and snails that were studied by other team members. In a sample sharing agreement developed with Dr. Volker Bluem, organizer of the CEBAS research program, we received a small number of the juveniles and shared the brains of two adult females.

  18. Adrenal insufficiency: diagnosis and management.

    Science.gov (United States)

    Munver, Ravi; Volfson, Ilya A

    2006-01-01

    Adrenal insufficiency is a disorder characterized by hypoactive adrenal glands resulting in insufficient production of the hormones cortisol and aldosterone by the adrenal cortex. This disorder may develop as a primary failure of the adrenal cortex or be secondary to an abnormality of the hypothalamic-pituitary axis. Patients with adrenal insufficiency often are asymptomatic or they may present with fatigue, muscle weakness, weight loss, low blood pressure, and sometimes darkening of the skin. The presentation of adrenal insufficiency varies dramatically and poses a major diagnostic dilemma. This review focuses on the diagnosis and treatment of primary and secondary adrenal insufficiency.

  19. Effect of Electroacupuncture at Gan Shu, Qi Men on Changes of Behaviors and Related Hormones of Hypothalamus - Pituitary - Adrenal Axis in Rats with Syndrome of Stagnation of Liver - Qi%电针肝俞、期门对肝气郁结模型大鼠行为学及HPA轴相关激素的影响

    Institute of Scientific and Technical Information of China (English)

    刘子旺; 赵海滨; 张秀静; 单保慈; 刘华; 贺立娟

    2011-01-01

    目的:探讨电针对肝气郁结模型大鼠行为学影响及下丘脑-垂体-肾上腺(HPA)轴相关激素的调节作用.方法:将Wistar大鼠30只随机分为正常对照组、肝郁模型组、电针治疗组,通过开野实验( Open - Field Test)及蔗糖水消耗实验进行大鼠行为学检测,运用ELISA法检测大鼠血清促肾上腺皮质激素释放激素(CRH)、皮质酮(CORT)含量,3组之间进行比较.结果:与正常组相比,模型组Open -Field Test水平运动得分和垂直运动得分明显减少,蔗糖水偏嗜度明显减少,血清CORT、CRH的含量明显升高,而电针明显增加模型大鼠的水平得分、垂直得分及蔗糖水偏嗜度,并可阻抑血清CRH、CORT的过度分泌.结论:肝气郁结大鼠存在活动度降低、探究行为减少、快感缺失和HPA轴亢进,电针肝俞、期门可抑制CRH、CORT的过度分泌,缓解HPA轴亢进,外在体现为对模型大鼠行为学的改善.%Objective:To investigate the effect of electroacupuncture (EA) on changes of behaviors and some related hormones of the hypothalamus - pituitary - adrenal ( HPA) axis in rats with stagnation of liver - qi syndrome. Methods:The rats were randomly divided into three groups; normal group, model group, EA group, n = 10. We judged the behavioral changes of model rats and the behavioral action of EA in treating the stagnation of liver - qi syndrome through Open - Field Test and partial addicted to sugar water test. The content of ad-renocorticotropic hormone - releasing hormone ( CRH ) and serum corticosterone ( CORT) were measured by ELJSA method. Results:The horizontal movement scores and vertical movement scores of rats in model group both significantly reduced compared with the normal group (P <0.01) ,as well as the degree of partial addicted to sugar water of model group rats decreased significantly ( P <0.01) . The content of CRH and CORT in serum of model group rats were significantly higher(P <0. 01). The horizontal movement

  20. Prenatal glucocorticoid exposure alters hypothalamic-pituitary-adrenal function and blood pressure in mature male guinea pigs.

    Science.gov (United States)

    Banjanin, Sonja; Kapoor, Amita; Matthews, Stephen G

    2004-07-01

    Pregnant guinea pigs were treated with dexamethasone (1 mg kg(-1)) or vehicle on days 40-41, 50-51 and 60-61 of gestation, after which animals delivered normally. Adult male offspring were catheterized at 145 days of age and subjected to tests of hypothalamic-pituitary-adrenal (HPA) axis function in basal and activated states. Animals exposed to dexamethasone in utero (mat-dex) exhibited increased hippocampus-to-brain weight ratio, increased adrenal-to-body weight ratio and increased mean arterial pressure. There were no effects on gestation length, birth weight and postnatal growth. There were no overall differences in diurnal plasma adrenocorticotropic hormone (ACTH) and cortisol profiles, though there were subtle differences during the subjective afternoon between control and mat-dex offspring. A significant decrease in initial ACTH suppression was observed following dexamethasone injection in mat-dex offspring compared to control offspring. Molecular analysis revealed significantly increased MR mRNA expression in the limbic system and particularly in the dentate gyrus in mat-dex offspring. In the anterior pituitary, both pro-opiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA levels were significantly elevated in mat-dex offspring. In conclusion, (1) repeated prenatal treatment with synthetic glucocorticoid (sGC) permanently programmes organ growth, blood pressure and HPA regulation in mature male offspring and these changes involve modification of corticosteroid receptor expression in the brain and pituitary; (2) the effects of prenatal sGC exposure on HPA function appear to change as a function of age, indicating the importance of investigating HPA and cardiovascular outcome at multiple time points throughout life.

  1. FSH and TSH in the Regulation of Bone Mass: The Pituitary/Immune/Bone Axis

    Directory of Open Access Journals (Sweden)

    Graziana Colaianni

    2013-01-01

    Full Text Available Recent evidences have highlighted that the pituitary hormones have profound effects on bone, so that the pituitary-bone axis is now becoming an important issue in the skeletal biology. Here, we discuss the topical evidence about the dysfunction of the pituitary-bone axis that leads to osteoporotic bone loss. We will explore the context of FSH and TSH hormones arguing their direct or indirect role in bone loss. In addition, we will focus on the knowledge that both FSH and TSH have influence on proinflammatory and proosteoclastogenic cytokine expression, such as TNFα and IL-1, underlining the correlation of pituitary-bone axis to the immune system.

  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. Baseline morning cortisol level as a predictor of pituitary-adrenal reserve: a comparison across three assays.

    Science.gov (United States)

    Sbardella, Emilia; Isidori, Andrea M; Woods, Conor P; Argese, Nicola; Tomlinson, Jeremy W; Shine, Brian; Jafar-Mohammadi, Bahram; Grossman, Ashley B

    2017-02-01

    The short ACTH stimulation test (250 μg) is the dynamic test most frequently used to assess adrenal function. It is possible that a single basal cortisol could be used to predict the dynamic response, but research has been hampered by the use of different assays and thresholds. To propose a morning baseline cortisol criterion of three of the most commonly used modern cortisol immunoassays - Advia Centaur (Siemens), Architect (Abbott) and the Roche Modular System (Roche) - that could predict adrenal sufficiency. Observational, retrospective cross-sectional study at two centres. Retrospective analysis of the results of 1019 Short Synacthen tests (SSTs) with the Advia Centaur, 449 SSTs with the Architect and 2050 SSTs with the Roche Modular System assay. Serum cortisol levels were measured prior to injection of 250 μg Synacthen and after 30 min. Overall, we were able to collate data from a total of 3518 SSTs in 3571 patients. Using receiver-operator curve analysis, baseline cortisol levels for predicting passing the SST with 100% specificity were 358 nmol/l for Siemens, 336 nmol/l for Abbott and 506 nmol/l for Roche. Utilizing these criteria, 589, 158 and 578 SSTs, respectively, for Siemens, Abbott and Roche immunoassays could have been avoided. We have defined assay-specific morning cortisol levels that are able to predict the integrity of the hypothalamo-pituitary-adrenal axis. We propose that this represents a valid tool for the initial assessment of adrenal function and has the potential to obviate the need for dynamic testing in a significant number of patients. © 2016 John Wiley & Sons Ltd.

  4. Total flavonoids extracted from xiaobuxin-tang on hyperactivity of hypothalamic-pituitary-adrenal axis in mouse learned helplessness model%小补心汤总黄酮对获得性无助小鼠的抗抑郁作用及其对HPA轴功能的影响

    Institute of Scientific and Technical Information of China (English)

    陈力; 张有志; 薛瑞; 于能江; 王玉露; 胡晓旭; 仇志坤; 赵楠; 李云峰; 徐江平

    2015-01-01

    Aim To investigate the effect of the total flaconoids extracted from Xiaobuxin-Tan g ( XBXT-2 ) on the hyperactivity of hypothalamic-pituitary-adrenal axis in mouse learned helplessness model. Methods Learned helplessness was induced by inescapable foot shock stress over 1h session for 5 days. After screen-ing, we divided learned helplessness mice into five groups:IS, inescapable shock;Dlx, dulxetine(20 mg ·kg-1);XBXT-2(25,50 mg·kg-1). Latency to es-cape shocks and escape failure had been recorded. During the test, Dlx(20 mg·kg-1 ) and XBXT-2(25, 50 mg·kg-1 ) were administered intragastrically once daily for four days. Serum corticosterone level and ad-renocorticotropic hormone ( ACTH ) level were meas-ured by ELISA, and expression of glucocorticoids re-ceptor ( GR) α/β and brain-derived neurotrophic fac-tor ( BDNF ) in hippocampus was determined using Western blot method. Results XBXT-2 (25,50 mg· kg-1 ) or duloxetine treatment showed antidepressant effect in mouse learned helplessness model, as demon-strated by the decreased escape failure and escape la-tency. Our ELISA results showed that XBXT-2 or du-loxetine significantly decreased serum corticosterone level and its upstream stress hormone ACTH level in learned helplessness mice. Furthermore, Western blot result demonstrated XBXT-2 treatment increased GRs and BDNF expression in hippocampus. Conclusions XBXT-2 produces significant antidepressant effect on learned helplessness mice. In addition, the modulation of HPA axis produced by XBXT-2 may be important mechanism underlying its antidepressant-like effect in mouse learned helplessness model.%目的:采用小鼠获得性无助模型评价小补心汤总黄酮(XBXT-2)的抗抑郁作用,并探究在应激状态下,XBXT-2对下丘脑-垂体-肾上腺轴( HPA)功能的调节作用。方法采用电脑程序控制的穿梭箱条件反射系统,给予不可逃避的足底电击诱导获得性无助模型,经过穿梭箱回避程序筛选,将成功诱导无

  5. 单相与双相抑郁患者执行功能及HPA轴释放功能的比较%A compared study on the executive functions and releases function of hypothalamus-pituitary-adrenal (HPA) axis in patients with single and bipolar depression disorder

    Institute of Scientific and Technical Information of China (English)

    李宏伟; 高镇松; 吴强; 黄佩珊

    2014-01-01

    目的:比较单相与双相抑郁患者执行功能及下丘脑-垂体-肾上腺(HPA)轴释放功能的差异。方法:对32例单相与31例双相抑郁患者于0、4和8周进行连线测验(TMT)、彩色文字阅读测验(Stroop-C、Stroop-CW ),同步测定24 h 尿17-羟皮质醇、24 h 尿游离皮质酮、血浆皮质醇,进行组间比较,并与28例健康者对照。结果:0和4周抑郁组的TMT-A、TMT-B、Stroop-C、Stroop-CW均显著长于对照组(P<0.01),血浆皮质醇显著高于对照组(P<0.01);0周单相组TMT-B、Stroop-C均显著长于双相组(P<0.01)。单相组和双相组0周血浆皮质醇低谷浓度不出现于12:00 AM ,午夜低谷现象消失,至4周午夜分泌低谷现象恢复。结论:在执行功能和HPA轴释放功能方面,单相与双相抑郁存在差异,需加以关注。%Objective To compare the executive functions and releases function of hypothalamus-pituitary-adrenal (HPA) axis in patients with single and bipolar depression disorder. Methods 32 single-phase depression (the single group) and 31 bipolar depression patients (the bipolar group) were enrolled in this study. The trail making test A and B and Stroop test (Stroop-C and Stroop-CW) were tested at 0,4 week and 8 week later. In addition,levels of 24-h urine 17-OH cortisol,24-h urine free corticosterone and plasma cortisol were also detrmined. The related results were compared among the two groups and 28 healthycontrol group. Results The TMT-A,TMT-B,Stroop-C and Stroop-CW of the baseline and at 4 week were significantly longer in the depression group than those in the control group(P<0.01,respectively), and the plasma cortisol was also higher in the depression group than that in the control (P<0.01). On baseline, the single group showed significantly longer TMT-B and Stroop-C than those in the bipolar group (P < 0.01, respectively). At 0 week, lower plasma cortisol concentrations did not appear at 12

  6. Multiscale mathematical modeling of the hypothalamo-pituitary-gonadal axis.

    Science.gov (United States)

    Clément, Frédérique

    2016-07-01

    Although the fields of systems and integrative biology are in full expansion, few teams are involved worldwide into the study of reproductive function from the mathematical modeling viewpoint. This may be due to the fact that the reproductive function is not compulsory for individual organism survival, even if it is for species survival. Alternatively, the complexity of reproductive physiology may be discouraging. Indeed, the hypothalamo-pituitary-gonadal (HPG) axis involves not only several organs and tissues but also intricate time (from the neuronal millisecond timescale to circannual rhythmicity) and space (from molecules to organs) scales. Yet, mathematical modeling, and especially multiscale modeling, can renew our approaches of the molecular, cellular, and physiological processes underlying the control of reproductive functions. In turn, the remarkable dynamic features exhibited by the HPG axis raise intriguing and challenging questions to modelers and applied mathematicians. In this article, we draw a panoramic review of some mathematical models designed in the framework of the female HPG, with a special focus on the gonadal and central control of follicular development. On the gonadal side, the modeling of follicular development calls to the generic formalism of structured cell populations, that allows one to make mechanistic links between the control of cell fate (proliferation, differentiation, or apoptosis) and that of the follicle fate (ovulation or degeneration) or to investigate how the functional interactions between the oocyte and its surrounding cells shape the follicle morphogenesis. On the central, mainly hypothalamic side, models based on dynamical systems with multiple timescales allow one to represent within a single framework both the pulsatile and surge patterns of the neurohormone GnRH. Beyond their interest in basic research investigations, mathematical models can also be at the source of useful tools to study the encoding and decoding of

  7. Lead Toxicity and The Hypothalamic-Pituitary-Testicular Axis

    Directory of Open Access Journals (Sweden)

    Nadia AIT HAMADOUCHE

    2013-02-01

    Full Text Available Environmental exposure to toxic levels of lead (Pb occurs in a number of industries with potential adverse effects on the reproductive capacity of exposed men. Clinical and animal studies indicate that abnormalities of spermatogenesis result from toxic lead exposure, but eventual histopathologic alterations involved have not been identified. To explore putative abnormalities in the reproductive gonadotropic axis following lead intoxication, experimental animals when exposed to low levels of lead, 65 days old animals were treated with distilled water containing 0, 0 mg (control, 10 mg lead (Pb/Kg/day and 15 mg lead (Pb/Kg/day intraperitoneally for 20 days. At the end of treatment, the animals were sacrificed and the blood collected for luteinizing hormone (LH and testosterone assays. The testis was processed for histological analysis. The results showed a high serum concentration of LH and testosterone in lead-treated animals compared to controls. Histological examination of testis showed deformities in testicular morphology of lead intoxicated animals with gross damage within the somniferous tubules. A strong correlation was established between LH and testosterone suggesting an alteration in the endocrine components of the gonadotropic axis. Histological examination of pituitary gland showed some degenerative changes in endocrine cells of lead group. Changes in LH and testosterone levels suggest that Pb exposure during the critical time of sexual differentiation induces reproductive axis abnormalities in adulthood. In conclusion, lead has a gonadotoxic effect by decreasing LH and testosterone levels and damaging the testis seminiferous tubules. Catalase activity was significantly reduced in the lead group following 65 days of exposure which possibly indicates that lead might had other mechanisms of action, such as increasing oxidative damage.

  8. Effect of reproductive status on hypothalamic-pituitary-adrenal (HPA) activity and reactivity in male California mice (Peromyscus californicus).

    Science.gov (United States)

    Harris, Breanna N; Saltzman, Wendy

    2013-03-15

    Previous studies indicate that reproductive condition can alter stress response and glucocorticoid release. Although the functional significance of hypothalamic-pituitary-adrenal (HPA) axis modulation by breeding condition is not fully understood, one possible explanation is the behavior hypothesis, which states that an animal's need to express parental behavior may be driving modulation of the HPA axis. This possibility is consistent with findings of blunted activity and reactivity of the HPA axis in lactating female mammals; however, effects of reproductive status on HPA function have not been well characterized in male mammals that express parental behavior. Therefore, we tested this hypothesis in the monogamous and biparental California mouse. Several aspects of HPA activity were compared in males from three reproductive conditions: virgin males (housed with another male), non-breeding males (housed with a tubally ligated female), and first-time fathers (housed with a female and their first litter of pups). In light of the behavior hypothesis we predicted that new fathers would differ from virgin and non-breeding males in several aspects of HPA function and corticosterone (CORT) output: decreased amplitude of the diurnal rhythm in CORT, a blunted CORT increase following predator-odor stress, increased sensitivity to glucocorticoid negative feedback, and/or a blunted CORT response to pharmacological stimulation. In addition, we predicted that first-time fathers would be more resistant to CORT-induced suppression of testosterone secretion, as testosterone is important for paternal behavior in this species. We found that virgin males, non-breeding males and first-time fathers did not display any CORT differences in diurnal rhythm, response to a predator-odor stressor, or response to pharmacological suppression or stimulation. Additionally, there were no differences in circulating testosterone concentrations. Adrenal mass was, however, significantly lower in new

  9. Facilitation of hypothalamic-pituitary-adrenal responses to novel stress following repeated social stress using the resident/intruder paradigm.

    Science.gov (United States)

    Bhatnagar, Seema; Vining, Courtenay

    2003-01-01

    Our goal in these studies was to characterize some specific aspects of hypothalamic-pituitary-adrenal (HPA) activity in rats exposed to repeated social stress. We used a modification of the resident/intruder paradigm in which male intruder rats were subjected to defeat and then separated from the resident by an enclosure for a total of 30 min on Day 1. On Days 2-7, intruder rats were exposed to different resident rats every day through a wire mesh enclosure for 30 min in order to minimize injurious physical contact between the two rats. The intruder rats gained significantly less weight than controls over the 7-day period of stress though basal corticosterone levels and adrenal and thymus weights were not significantly different between the two groups. On Day 8, repeatedly stressed rats exhibited facilitation of HPA responses to novel restraint compared to controls but no differences in negative feedback sensitivity to dexamethasone (0.05 or 0.2 mg/kg) were observed. Thus, the HPA axis of socially stressed rats remains responsive to a stimulus that has never been encountered. Using this type of repeated presentation to an aggressive resident allows us to examine the neuroendocrine and behavioral consequences, and their underlying neural mechanisms, of exposure to a stressor that is social in nature and naturalistic for rodents.

  10. Response of the Hypothalamic-Pituitary-Adrenal System to Repeated Moderate Psychoemotional Stress Exposure Is Associated with Behavioral Parameters.

    Science.gov (United States)

    Goncharova, N D; Chigarova, O A; Oganyan, T E

    2017-05-01

    Individual features of the response of the hypothalamic-pituitary-adrenal axis (HPAA) to repeated moderate stress exposure (daily 2-h restraint stress for 10 days) was studied in young female rhesus monkeys with healthy normal behavior and combined group of female rhesus monkeys with abnormal depression-like and anxious behavior. No between-group differences in the response of ACTH and cortisol were found on day 1. On day 10, a rapid and less pronounced increase in ACTH secretion was observed in all animals in comparison with day 1. Analysis of between-group differences in HPAA response showed higher increase in ACTH level and lower increase in cortisol concentration in animals with depression-like and anxious behavior. These changes were similar to the previously described differences in the response of the adenohypophysis and adrenal cortex to acute restraint stress in old monkeys with similar behavior. Thus, individuals with depression-like and anxious behavior demonstrate impaired stress-induced reactivity of HPAA as early as in young age.

  11. 下丘脑室旁核组胺H3受体对哮喘大鼠下丘脑-垂体-肾上腺轴功能的调控%Effect of histamine H3 receptor in the hypothalamic paraventricular nuclei on hypothalamic-pituitary-adrenal axis in rats with asthma

    Institute of Scientific and Technical Information of China (English)

    季吉; 董榕

    2011-01-01

    Objective: To determine whether histamine H3 receptor in the hypothalamic paraventricular nuclei (PVN) regulates the function of hypothalamic-pituitary-adrenal (HPA) axis in rats with asthma. Method: Rat model for asthma was established by Elwood's methods. A stainless steel jacket was implanted into the PVN using a technique of central three-dimensional position, and R(α)-methylhistamine [R-(α)-MeHA, a H3 receptor agonist] 2 μg or thioperamide (a H3 receptor antagonist) 5 μg was injected into the PVN. Levels of histamine in PVN were detected by high-performance liquid chromatography, and the concentrations of CRH in median eminence, ACTH and CORT in plasma were detected by the radioimmunoassay. Relative levels of IL-10 in both hypothalataus tissue and plasma were measred by double-ligand-linked immunosorbent assay. Result: Levels of histamine in PVN decreased significantly, whereas the concentrations of CRH in median eminence, ACTH and CORT in plasma and the levels of IL-lO in both hypothalamus tissue and plasma were all increased significantly in acute episode asthms rats with treatment of R-(α)-MeHA compared with control rats, and these responses were blocked by treatment of thioperamide, a H3 receptors specific antagonist. Conclusion: Specific activation histamine H3 receptors in PVN can improve the function of HPA in rats with asthma.%目的:探讨哮喘大鼠下丘脑室旁核(paraventricular nuclei,PVN)内组胺H3受体对下丘脑-垂体-肾上腺轴(HPA)功能的调控.方法:根据Elwood方法,制备哮喘模型.采用中枢立体定位技术,在PVN内微量注射组胺H3受体激动剂R-(α)-甲基组胺[R-(α)-methylhistamine,R-(α)-MeHA]2 μg或组胺H3受体拮抗剂Thioperamide 5 μg,注射药物体积均为1μl.高效液相色谱法检测PVN内组胺含量;放射免疫分析方法检测正中隆起中促肾上腺皮质激素释放激素(CRH)和外周血中促肾上腺皮质激素(ACTH)、皮质酮(CORT)含量;酶联免疫吸附法(ELISA

  12. Adrenal and gonadal steroids and pituitary response to LHRH in girls. II. Precocious puberty.

    Science.gov (United States)

    Pintor, C; Genazzani, A R; Ibba, P; Pecciarini-Snickars, L; Corda, R

    1978-04-01

    Three baby girls between 22 and 30 months of age, presenting with isosexual idiopathic precocious puberty apparently not due to any organic cause, were studied. Basal levels of plasma steroids of adrenal and gonadal origin, circadian rhythm of plasma cortisol, and pituitary response to 25 microgram of LHRH were evaluated. All cases were characterized by high levels of plasma gonadotropins and by a marked response to exogenous LHRH. Normal cortisol circadia rhythm was found in all cases, one of which characterized by slightly raised plasma values. The other adrenal steroids were all higher than those expected for the chronological age, corresponding to those of 5-6 years old girls. On the other hand, steroids of both adrenal and ovarian (A, T) or mainly ovarian origin (E2) and DHT were all found to be higher than those normally reported in girls at stage 2 of sexual development. These data indicate a hypersecretion of gonadotropins in idiopathic isosexual precocious puberty, with a marked gonadal steroidogenetic response. The secretion of adrenal androgens does not appear to have an important role in the etiology of this condition.

  13. 注意力缺陷多动障碍儿童下丘脑-垂体-肾上腺轴的功能研究%Function of the hypothalamus-pituitary-adrenal axis in children with attention deficit hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    陈燕惠; 陈辉; 刘艳艳; 林桂秀; 韦立新; 陈丹玲

    2009-01-01

    目的 通过研究注意力缺陷多动障碍(ADHD)儿童下丘脑-垂体-肾上腺轴(HPA)的功能状态,探讨HPA轴在ADHD发生中的作用.方法 128例6~14岁ADHD男童根据DSM-IV ADHD诊断和分型标准,其中注意缺陷为主型(ADHD-I)44例,多动-冲动为主型(ADHD-HI)32例,混合型(ADHD-C)52例,对照组为年龄匹配健康男童30名,于8:00 am空腹采血.分别采用全自动微粒酶免疫分析法及电化学发光法检测血浆皮质醇及促肾上腺皮质激素(ACTH),智力测验采用瑞文标准推理测验.结果 ADHD组IQ(84.5±11.3)低于对照组(94.6±12.4,P<0.01),ADHD 3个亚型组间比较差异有显著性(P<0.01),ADHD-I和ADHD-C两个亚组IQ水低于对照组(P<0.01),ADHD-HI组与对照组比较差异无显著性.ADHD组血浆皮质醇水平(226.5±129.1 mnol/L)较对照组(384.5±141.4 nmol/L)明显降低(P<0.01),ADHD-HI组(154.4±71.6 nmol/L)下降程度较ADHD-I组(219.4±117.7 nmol/L)及ADHD-C组(258.3±136.4 nmol/L)为著(P<0.01),而ADHD各组血浆ACTH水平与对照组比较差异无显著性.结论 在非应激状态下ADHD儿童存在着HPA轴调节功能障碍,这可能系HPA轴低反应性所致.低血浆皮质醇对认知行为影响较小,而与注意缺陷、多动、冲动行为关系更为密切.%Objective To study the function of the hypothalamus-pituitary-adrenal (HPA) axis in children with attention deficit hyperactivity disorder (ADHD). Methods One hundred and twenty-eight boys with ADHD at ages of 6 to 14 years were enrolled. The diagnosis and grouping of ADHD were based on the Diagnostic and Statistical Manual of Mental Disorders ( DSM-IV) : ADHD-predominantly inattention type (ADHD-I, n =44), ADHD-predominantly hyperactive impulsivetype (ADHD-HI, n = 32) and ADHD-combined type (ADHD-C, n =52). Thirty healthy boys served as the control group. Plasma levels of cortisol and adrenocorticotropic hormone ( ACTH) were measured by automatic particle enzyme immunoassay and electrochemiluminescence

  14. DAX-1基因突变所致先天性肾上腺发育不良患者下丘脑-垂体-睾丸轴功能分析%Dysfunction of hypothalamic-pituitary-testicular axis in patients with adrenal hypoplasia congenita due to DAX-1 gene mutation

    Institute of Scientific and Technical Information of China (English)

    郑俊杰; 伍学焱; 聂敏; 刘兆祥; 王曦; 黄炳昆; 付勇; 卢琳; 段炼

    2016-01-01

    目的 分析DAX-1基因突变所致X连锁先天性肾上腺发育不良(AHC)患者下丘脑-垂体-睾丸轴(HPTA)功能损伤的部位、程度及生精疗效.方法 回顾性分析北京协和医院2007年11月至2014年12月收治的经基因测序确诊为DAX-1基因突变的24例成年男性患者的临床表现、激素测定和精液分析结果,探讨其HPTA功能损伤的部位及程度.结果 所有患者均有原发性肾上腺皮质功能减退症的表现,21例(87.5%)患者在10岁前发病.患者治疗前睾丸体积2.0(2.0,3.8) ml,3例有隐睾史.经人绒毛膜促性腺激素(HCG)刺激后(16例),血总睾酮从0.1(0,0.5) nmol/L升高至13.5(7.6,15.4) nmol/L.23例患者确诊为低促性腺激素性性腺功能减退症(HH);仅1例患者的血促性腺激素[黄体生成素(LH) 5.2 U/L,卵泡刺激素(FSH) 15.7 U/L]和睾酮水平(13.4 nmol/L)均正常,但精液中无精子.7例患者接受HCG联合人绝经期促性腺激素(HMG)治疗,总治疗时间为80人月,治疗期间血总睾酮水平达15.3(8.4,25.3) nmol/L;睾丸体积从(4.0±2.9) ml增加到(4.9±3.3)ml,但差异无统计学意义(P =0.270),均未见到精子生成.另1例患者接受GnRH脉冲治疗2个月,LH从1.0 U/L增加至9.3 U/L,FSH从3.0 U/L增加至13.5 U/L,总睾酮从0 nmol/L增加至10.0 nmol/L,但治疗前后睾丸体积均为3 ml.结论 DAX-1基因突变所致AHC患者HPTA功能损伤主要表现为HH和原发性生精障碍.患者睾丸间质细胞功能基本正常,但支持细胞和曲细精管功能低下,呈现间质细胞功能和曲细精管功能明显分离.%Objective To evaluate the hypothalamic-pituitary-testicular axis (HPTA) function and spermatogenesis in male patients with X-linked adrenal hypoplasia congenita (AHC) due to DAX-1 gene mutation.Methods Twenty-four adult male patients from Peking Union Medical College Hospital between November 2007 and December 2014 were included.Their DAX-1 gene mutations were confirmed by polymerase chain reaction (PCR

  15. HPG-axis hormones during puberty : A study on the association with hypothalamic and pituitary volumes

    NARCIS (Netherlands)

    Peper, Jiska S.; Brouwer, Rachel M.; van Leeuwen, Marieke; Schnack, Hugo G.; Boomsma, Dorret I.; Kahn, Rene S.; Pol, Hilleke E. Hulshoff

    2010-01-01

    Objective: During puberty, the hypothalamus-pituitary-gonadal (HPG) axis is activated, leading to increases in luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex steroids (testosterone and estradiol) levels. We aimed to study the association between hypothalamic and pituitary volum

  16. DMPD: The role of macrophages in the hypothalamic-pituitary-adrenal activation inresponse to endotoxin (LPS). [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 1315450 The role of macrophages in the hypothalamic-pituitary-adrenal activation in...png) (.svg) (.html) (.csml) Show The role of macrophages in the hypothalamic-pituitary-adrenal activation in...response to endotoxin (LPS). PubmedID 1315450 Title The role of macrophages in th

  17. Hypopituitarism in the elderly: a narrative review on clinical management of hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes dysfunction.

    Science.gov (United States)

    Curtò, L; Trimarchi, F

    2016-10-01

    Hypopituitarism is an uncommon and under-investigated endocrine disorder in old age since signs and symptoms are unspecific and, at least in part, can be attributed to the physiological effects of aging and related co-morbidities. Clinical presentation is often insidious being characterized by non-specific manifestations, such as weight gain, fatigue, low muscle strength, bradipsychism, hypotension or intolerance to cold. In these circumstances, hypopituitarism is a rarely life-threatening condition, but evolution may be more dramatic as a result of pituitary apoplexy, or when a serious condition of adrenal insufficiency suddenly occurs. Clinical presentation depends on the effects that each pituitary deficit can cause, and on their mutual relationship, but also, inevitably, it depends on the severity and duration of the deficit itself, as well as on the general condition of the patient. Indeed, indications and methods of hormone replacement therapy must include the need to normalize the endocrine profile without contributing to the worsening of intercurrent diseases, such as those of glucose and bone metabolism, and the cardiovascular system, or to the increasing cancer risk. Hormonal requirements of elderly patients are reduced compared to young adults, but a prompt diagnosis and appropriate treatment of pituitary deficiencies are strongly recommended, also in this age range.

  18. Establishment of syndrome of stagnation of liver Qi model in rats and primary study on related hormones of hypothalamus-pituitary-adrenal axis%肝气郁结证动物模型的建立及HPA轴相关激素的初步研究

    Institute of Scientific and Technical Information of China (English)

    赵海滨; 刘子旺; 张秀静

    2011-01-01

    [目的]建立并验证“肝气郁结证”大鼠模型,在此基础上研究“肝气郁结证”下丘脑-垂体-肾上腺(HPA)轴相关激素的改变.[方法]20只Wistar大鼠随机分为对照组、模型组.采用慢性应激+孤养方法制备“肝气郁结证”大鼠模型,通过行为学观察、蔗糖水偏嗜实验、开野实验评价模型.运用酶联免疫吸附试验( ELISA)技术对两组大鼠血清进行HPA轴相关激素分析.[结果]肝气郁结模型大鼠表现为躲避、活动减少、大便松散、皮色失去光泽,造模第2周开始生长较对照组缓慢,摄食量减少(P<0.05);28 d造模后,水平得分、垂直得分较正常组均明显降低(P<0.01,P<0.05),血清皮质酮(CORT)、促肾上腺皮质激素释放激素(CRH)的含量明显升高(P<0.01).[结论]从病因学、行为学和症状表现上成功构建了肝郁证大鼠模型,并进一步证实模型大鼠呈HPA轴亢进状态,有助于阐释肝郁证病理改变的本质.%[Objective] To establish and validate the syndrome of stagnation of liver Qi model in rats. The change of hormones related to hypothalamus-pituitary-adrenal (HPA) axis was investigated. [Methods] Twenty rats were randomly divided into two groups: control group and model group. We adopted the method of chronic stress combining with isolated breeding to prepare the model in rats with the stagnation of liver-Qi syndrome. Open-Field test and partial addicted to sugar water test were carried out one the day before experiments and after experiments. The rat's body weight and food intake in 24 h were recorded on the day before experiments, and on the 4th , 8th, 12th, 16th, 20th, 24th and 28th day during experiments respectively. The content of adrenocorticotropic hormone-releasing hormone (CRH) and serum corticosterone (CORT) were measured by ELISA method. [Results] There were some appearance of abnormal behaviors, such as decrease of elusion, slackness, looser stools, and matte fur among model

  19. Prenatal stress induces long-term effects in cell turnover in the hippocampus-hypothalamus-pituitary axis in adult male rats.

    Directory of Open Access Journals (Sweden)

    Eva Baquedano

    Full Text Available Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day. Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations.

  20. Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats

    Science.gov (United States)

    Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.

    2011-01-01

    Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

  1. [THE INFLUENCE OF MELANIN ON THE GASTRIC MUCOSA AND HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL AXIS UNDER ACUTE STRESS CONDITIONS].

    Science.gov (United States)

    Golyshkin, D V; Falalyeyeva, T M; Neporada, K S; Beregova, T V

    2015-01-01

    We studied the influence of melanin from yeast-like fungi Nadsoniella nigra strain X1 on the changes of the levels of adrenocorticotropic hormone (ACTH) and cortisol in blood serum of rats, adrenal glands weight ratio and lesions of the gastric mucosa (GM) caused by neuromuscular tension by Selye. Melanin administration restored functioning of the hypothalamic-pituitary-adrenal axis that was evident by an increase of ACTH concentration by 42% and a decrease of cortisol concentration by 19% compared to the rats injected with water (group 2). In rats treated with melanin, the adrenal glands weight ratio, didn't differ from intact control group of the rats. Melanin decreased ulcers area by 64% and reduced the content of free hydroxyproline by 29%, the free fucose by 16% and the free hexuronic acids by 24% in the GM compared to the group 2 of the rats. It is established that the mechanism of melanin stress-protective properties are based on its regulation of the glucocorticoids secretion and prevention of GM collagen and extracellular matrix substances depolymerization. Melanin possesses gastroprotective properties and is a perspective agent for preventing and treatment of consequences of the stress influence on the organism.

  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

    The distribution of the proopiomelanocortin-derivated amidated joining peptide (JP-N) was examined in the human pituitary gland, adrenal gland, gut and in three bronchial carcinoids. Double immunostaining showed coexistence of immunoreactive JP-N and other proopiomelanocortin derivatives, e...

  3. Effects of Parental Depressive Symptoms on Child Adjustment Moderated by Hypothalamic Pituitary Adrenal Activity: Within- and between-Family Risk

    Science.gov (United States)

    Laurent, Heidemarie K.; Leve, Leslie D.; Neiderhiser, Jenae M.; Natsuaki, Misaki N.; Shaw, Daniel S.; Fisher, Philip A.; Marceau, Kristine; Harold, Gordon T.; Reiss, David

    2013-01-01

    Child hypothalamic pituitary adrenal (HPA) activity was investigated as a moderator of parental depressive symptom effects on child behavior in an adoption sample ("n" = 210 families). Adoptive parents' depressive symptoms and child internalizing and externalizing were assessed at 18, 27, and 54 months, and child morning and evening HPA…

  4. [Changes in the activity of sympathetic-adrenal medullary system and hypothalamic-pituitary-adrenal system in humans exposed to psychogenic stressors and their effects on immunoreactivity].

    Science.gov (United States)

    Simić, Natasa

    2010-10-01

    This paper gives an account of the functioning of the two systems in different stress induced situations. The activation of the sympathetic-adrenal medullary system is accompanied by the release of catecholamines, while the increased activity of the hypothalamic-pituitary-adrenal system results in the increased release of corticosteroids, especially cortisol. The role of the sympathetic-adrenal medullary system was investigated in immunologic changes induced by laboratory stressors. In the real, as in laboratory conditions, the effects of different stressors on the level of cortisol were studied, as it is the final product of the hypothalamic-pituitary-adrenal system activity. Additional (negative) effects on the functioning of these systems could induce some variables, as an increased consumption of alcohol, smoking, and sleeping disorder. Furthermore, the methodological shortcomings and the selection of subjects in previous studies are discussed. Previous results are also discussed, such as the immunosuppressive effects of cortisol, as well as the mediator and moderator variables in relation to stress and immunoreactivity.

  5. Atrial natriuretic factor: radioimmunoassay and effects on adrenal and pituitary glands

    Energy Technology Data Exchange (ETDEWEB)

    Gutkowska, J.; Horky, K.; Schiffrin, E.L.; Thibault, G.; Garcia, R.; De Lean, A.; Hamet, P.; Tremblay, J.; Anand-Srivastava, M.B.; Januszewicz, P.

    1986-06-01

    A simple and sensitive radioimmunoassay was developed for measurement of immunoreactive atrial natriuretic factor (IR-ANF) in rat and human plasma and in rat atria. The two atria contain about 20 ..mu..g ANF per rat. The right atrium contained 2.5 times more ANF than did the left. Ether anesthesia and morphine markedly increased IR-ANF in rat plasma. The concentration of IR-ANF in plasma of clinically normal human subjects was 65.3 +/- 2.5 pg/ml. Paroxysmal tachycardia and rapid atrial pacing significantly increased IR-ANF in human plasma. Two- to seven-fold higher concentrations were found in coronary sinus blood than in the peripheral circulation. In the plasma of rats and humans, circulating ANF is probably a small-molecular-weight peptide. ANF acts on the adrenal and the pituitary. ANF inhibits aldosterone secretion from rat zona glomerulosa and steroid secretion by bovine adrenal zona glomerulosa and fasciculata. ANF stimulated the basal secretion of arginine vasopressin (AVP) in vitro and inhibited KCl-stimulated release of AVP.

  6. Takotsubo cardiomyopathy in a patient with pituitary adenoma and secondary adrenal insufficiency

    Directory of Open Access Journals (Sweden)

    Georgene Singh

    2015-01-01

    Full Text Available We describe a case of Takotsubo cardiomyopathy in a case of pituitary macroadenoma in acute adrenal crisis. A 48-year-old man presented with acute onset altered sensorium, vomiting, and gasping. On admission, he was unresponsive and hemodynamically unstable. He was intubated and ventilated and resuscitated with fluids and inotropes. The biochemical evaluation revealed hyponatremia, hyperkalemia, and hypocortisolism. Hyponatremia was corrected with 3% hypertonic saline. Contrast enhanced computed tomography (CT scan of the brain revealed a sellar-suprasellar mass with hypothalamic extension with no evidence of pituitary apoplexy. A diagnosis of invasive pituitary adenoma with the Addisonian crisis was made and steroid replacement was initiated. Despite volume resuscitation, he had persistent refractory hypotension, recurrent ventricular tachycardia, and metabolic acidosis. Electrocardiogram (ECG showed ST elevation and T-wave inversion in lateral leads; cardiac-enzymes were increased suggestive of acute coronary syndrome. Transthoracic echocardiography showed severe regional wall motion abnormalities (RWMAs involving left anterior descending territory and low ejection fraction (EF. Coronary angiogram revealed normal coronaries, apical ballooning, and severe left ventricular dysfunction, consistent with a diagnosis of Takotsubo′s cardiomyopathy. Patient was managed with angiotensin-converting enzyme inhibitors and B-blockers. He improved over few days and recovered completely. At discharge, ECG changes and RWMA resolved and EF normalized to 56%. In patients with Addisonian Crisis with persistent hypotension refractory to optimal resuscitation, possibility of Takotsubo′s cardiomyopathy should be considered. Early recognition of association of Takotsubos cardiomyopathy in neurological conditions, prompt resuscitation, and supportive care are essential to ensure favorable outcomes in this potentially lethal condition.

  7. Hyperprolactinaemia is associated with a higher prevalence of pituitary-adrenal dysfunction in non-functioning pituitary macroadenoma

    NARCIS (Netherlands)

    Tjeerdsma, Geert; Sluiter, WJ; Hew, JM; Molenaar, WM; deLange, WE; Dullaart, RPF

    1996-01-01

    In non-functioning pituitary macroadenoma (NFMA), hyperprolactinaemia (hyperPRL) is considered to be a sign of hypothalamic-pituitary dysregulation, but it is unknown whether hyperPRL is associated with an increased frequency of pituitary hormone deficiencies. Forty consecutive patients with histolo

  8. The hypothalamic-pituitary axis in men and women with chronic kidney disease.

    Science.gov (United States)

    Holley, Jean L

    2004-10-01

    Although the precise abnormalities that lead to failure of the hypothalamic-pituitary-gonadal axis in men and women with chronic kidney disease (CKD) and end-stage renal disease (ESRD) remains undefined, evidence exists for defects in both the hypothalamus and the pituitary. The lack of appropriate cyclic release of gonadotropin-releasing hormone (GnRH) by the hypothalamus leads to loss of normal pulsatile luteinizing hormone (LH) release by the pituitary, which results in impaired ovulation in women and reduced testosterone and sperm production in men. The cause of impaired cyclic release of GnRH is unclear, but hyperprolactinemia, elevated endorphins, and high levels of GnRH and LH caused by reduced clearance may contribute. Perturbations of the hypothalamic-pituitary-gonadaotropin axis in CKD lead to high rates of infertility, dysfunctional uterine bleeding, and impaired puberty in children. Only through additional study of the complex effects of CKD on the hypothalamic-pituitary-gonadal axis will the precise abnormalities in hormonal control of reproduction be explained.

  9. The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis.

    Science.gov (United States)

    Tsatsanis, Christos; Dermitzaki, Eirini; Avgoustinaki, Pavlina; Malliaraki, Niki; Mytaras, Vasilis; Margioris, Andrew N

    2015-01-01

    Adipose tissue produces factors, including adipokines, cytokines and chemokines which, when released, systemically exert endocrine effects on multiple tissues thereby affecting their physiology. Adipokines also affect the hypothalamic-pituitary-gonadal (HPG) axis both centrally, at the hypothalamic-pituitary level, and peripherally acting on the gonads themselves. Among the adipokines, leptin, adiponectin, resistin, chemerin and the peptide kisspeptin have pleiotropic actions on the HPG axis affecting male and female fertility. Furthermore, adipokines and adipose tissue-produced factors readily affect the immune system resulting in inflammation, which in turn impact the HPG axis, thus evidencing a link between metabolic inflammation and fertility. In this review we provide an overview of the existing extensive bibliography on the crosstalk between adipose tissue-derived factors and the HPG axis, with particular focus on the impact of obesity and the metabolic syndrome on gonadal function and fertility.

  10. Population pharmacokinetic/pharmacodynamic modelling of the hypothalamic-pituitary-gonadal axis

    OpenAIRE

    2005-01-01

    The present thesis deals with different aspects of population pharmacokinetic/ pharmacodynamic (PK/PD) modelling of the male hypothalamic-pituitary-go-nadal (HPG) axis. The thesis consists of a summary report and five scientific research papers. An overview of the main topics covered in the thesis is provided in the summary report including PK/PD modelling in drug development, the pathological, physiological, and pharmacological aspects of the male HPG axis, and a detailed description of the ...

  11. Central regulation of the hypothalamo-pituitary-thyroid (HPT) axis: focus on clinical aspects.

    Science.gov (United States)

    Fliers, E; Boelen, A; van Trotsenburg, A S P

    2014-01-01

    The hypothalamus is the most prominent brain region involved in setpoint regulation of the thyroid axis. It generates the diurnal thyroid-stimulating hormone (TSH) rhythm, and it plays a central role in the adaptation of the thyroid axis to environmental factors such as caloric deprivation or infection. Many studies, including studies in human post-mortem tissue samples, have confirmed a key role for the thyrotropin-releasing hormone (TRH) neuron in the hypothalamic paraventricular nucleus (PVN) in thyroid axis regulation. In addition to their negative feedback action on TRH neurons in the hypothalamus, intrahypothalamic thyroid hormones can also modulate metabolism in adipose tissue and the liver via the autonomic nervous system. Congenital or acquired dysfunction of the hypothalamus or pituitary gland may result in central hypothyroidism (CeH). In the Netherlands, the prevalence of permanent congenital CeH as detected by neonatal screening is approximately 1 in 18000. In most neonates congenital CeH is accompanied by additional anterior pituitary hormone deficiencies, and many show clear morphological abnormalities such as a small anterior gland, a thin or absent pituitary stalk, or an ectopic posterior pituitary gland. Recently, a mutation in the immunoglobulin superfamily member 1 (IGSF1) gene was reported as a novel cause of X-linked, apparently isolated CeH occurring in neonates, children and adults. In adults, the most frequent cause of acquired CeH is a pituitary macroadenoma, usually accompanied by other pituitary hormone deficiencies. Central hyperthyroidism is a rare disorder, especially in children. In adults, it is mostly caused by a TSH-secreting pituitary adenoma. © 2014 Elsevier B.V. All rights reserved.

  12. Leptin plasma concentrations, leptin gene expression, and protein localization in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes of the European beaver (Castor fiber).

    Science.gov (United States)

    Chojnowska, Katarzyna; Czerwinska, Joanna; Kaminski, Tadeusz; Kaminska, Barbara; Kurzynska, Aleksandra; Bogacka, Iwona

    2017-01-01

    The European beaver (Castor fiber) is the largest seasonal free-living rodent in Eurasia. Since the physiology and endocrine system of this species remains unknown, the present study aimed to determine plasma leptin concentrations and the expression of the leptin gene and protein in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal (HPG and HPA) axes of beavers during breeding (April), postbreeding (July), and prebreeding (November) seasons. Leptin plasma concentrations did not change in females, whereas in males, leptin plasma concentrations were higher in July than those in April. The presence of leptin mRNA and protein was found in all examined tissues. In females, leptin mRNA expression in the hypothalamus, pituitary, ovaries, and myometrium was markedly higher in July than that in April. In males, leptin mRNA levels varied across the examined tissues of the HPG and HPA. Leptin synthesis increased in the hypothalamus during breeding and postbreeding seasons, but seasonal changes were not observed in the pituitary. In turn, testicular leptin levels were higher during breeding and prebreeding stages. Seasonal differences in the concentrations of leptin mRNA were also observed in the adrenal cortex. In males, leptin mRNA levels were higher in November than those in April or July. In females, leptin synthesis increased in the adrenal cortex during pregnancy relative to other seasons. This is the first ever study to demonstrate seasonal differences in leptin expression in beaver tissues, and our results could suggest that leptin is involved in the regulation of the HPG and HPA axes during various stages of the reproductive cycle in beavers. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Cat odor causes long-lasting contextual fear conditioning and increased pituitary-adrenal activation, without modifying anxiety.

    Science.gov (United States)

    Muñoz-Abellán, Cristina; Daviu, Nuria; Rabasa, Cristina; Nadal, Roser; Armario, Antonio

    2009-10-01

    A single exposure to a cat or cat odors has been reported by some groups to induce contextual and auditory fear conditioning and long-lasting changes in anxiety-like behaviour, but there is no evidence for parallel changes in biological stress markers. In the present study we demonstrated in male rats that exposure to a novel environment containing a cloth impregnated with cat fur odor resulted in avoidance of the odor, lower levels of activity and higher pituitary-adrenal (PA) response as compared to those exposed to the novel environment containing a clean cloth, suggesting increased levels of stress in the former animals. When re-exposed 9 days later to the same environment with a clean cloth, previously cat fur exposed rats again showed avoidance of the cloth area and lower levels of activity, suggesting development of contextual fear conditioning, which again was associated with a higher PA activation. In contrast, unaltered both anxiety-like behaviour and PA responsiveness to an elevated plus-maze were found 7 days after cat odor exposure. It is concluded that: (i) PA activation is able to reflect both the stressful properties of cat fur odor and odor-induced contextual fear conditioning; (ii) development of cat odor-induced contextual fear conditioning is independent of the induction of long-lasting changes in anxiety-like behaviour; and (iii) greater PA activation during exposure to the odor context is not explained by non-specific sensitization of the PA axis caused by previous exposure to cat fur odor.

  14. Increased hypothalamic-pituitary-adrenal drive is associated with decreased appetite and hypoactivation of food motivation neurocircuitry in anorexia nervosa

    Science.gov (United States)

    Lawson, Elizabeth A.; Holsen, Laura M.; DeSanti, Rebecca; Santin, McKale; Meenaghan, Erinne; Herzog, David B.; Goldstein, Jill M.; Klibanski, Anne

    2013-01-01

    Objective Corticotropin releasing hormone (CRH)-mediated hypercortisolemia has been demonstrated in anorexia nervosa (anorexia), a psychiatric disorder characterized by food restriction despite low body weight. While CRH is anorexigenic, downstream cortisol stimulates hunger. Using a food-related fMRI paradigm, we have demonstrated hypoactivation of brain regions involved in food motivation in women with anorexia, even after weight-recovery. The relationship between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and appetite, and the association with food motivation neurocircuitry hypoactivation is unknown in anorexia. We investigated the relationship between HPA activity, appetite and food motivation neurocircuitry hypoactivation in anorexia. Design Cross-sectional study of 36 women [13 anorexia (AN), 10 weight-recovered AN (ANWR), 13 healthy controls (HC)]. Methods Peripheral cortisol and ACTH levels were measured fasting and 30, 60, and 120min after a standardized mixed meal. The Visual Analogue Scale was used to assess homeostatic and hedonic appetite. fMRI was performed during visual processing of food and non-food stimuli to measure brain activation pre- and post-meal. Results In each group, serum cortisol levels decreased following the meal. Mean fasting, 120min post-meal, and nadir cortisol levels were high in AN vs. HC. Mean postprandial ACTH levels were high in ANWR compared to HC and AN. Cortisol levels were associated with lower fasting homeostatic and hedonic appetite, independent of BMI and depressive symptoms. Cortisol levels were also associated with between-group variance in activation in food-motivation brain regions (e.g., hypothalamus, amygdala, hippocampus, OFC and insula). Conclusions HPA activation may contribute to the maintenance of anorexia by suppression of appetitive drive. PMID:23946275

  15. Translational relevance of rodent models of hypothalamic-pituitary-adrenal function and stressors in adolescence

    Directory of Open Access Journals (Sweden)

    Cheryl M. McCormick

    2017-02-01

    Full Text Available Elevations in glucocorticoids that result from environmental stressors can have programming effects on brain structure and function when the exposure occurs during sensitive periods that involve heightened neural development. In recent years, adolescence has gained increasing attention as another sensitive period of development, a period in which pubertal transitions may increase the vulnerability to stressors. There are similarities in physical and behavioural development between humans and rats, and rats have been used effectively as an animal model of adolescence and the unique plasticity of this period of ontogeny. This review focuses on benefits and challenges of rats as a model for translational research on hypothalamic-pituitary-adrenal (HPA function and stressors in adolescence, highlighting important parallels and contrasts between adolescent rats and humans, and we review the main stress procedures that are used in investigating HPA stress responses and their consequences in adolescence in rats. We conclude that a greater focus on timing of puberty as a factor in research in adolescent rats may increase the translational relevance of the findings.

  16. Increased Hair Cortisol Concentrations and BMI in Patients With Pituitary-Adrenal Disease on Hydrocortisone Replacement.

    Science.gov (United States)

    Staufenbiel, Sabine M; Andela, Cornelie D; Manenschijn, Laura; Pereira, Alberto M; van Rossum, Elisabeth F C; Biermasz, Nienke R

    2015-06-01

    Intrinsic imperfections and lack of reliable biomarkers preclude optimal individual dosing of hydrocortisone replacement in adrenal insufficiency (AI). However, the clinical relevance of optimal dosing is exemplified by frequently occurring side effects of overreplacement and the dangers of underreplacement. Cortisol in scalp hair has been identified as a retrospective biomarker for long-term cortisol exposure. We compared hair cortisol concentrations (CORT(hair)) of patients with primary or secondary AI on replacement therapy with those of patient controls with a pituitary disease without AI (PCs) and of healthy controls (HCs). In this cross-sectional study, hair samples and anthropometric data were collected in 132 AI patients (52 males), 42 PCs (11 males), and 195 HCs (90 males). The proximal 3 cm of hair were used. CORT(hair) were measured using an ELISA. CORT(hair) were higher in AI patients than in HCs and PCs (P < .001), and hydrocortisone dose correlated with CORT(hair) (P = .04). Male AI patients demonstrated higher CORT(hair) than female patients (P < .001). AI patients had higher body mass index (BMI) than HCs (P < .001), and BMI correlated with CORT(hair) in the whole sample (P < .001). Physiological hydrocortisone replacement is associated with increased CORT(hair). The association between CORT(hair) and BMI could suggest a mild overtreatment that may lead to adverse anthropomorphic side effects, especially in males. CORT(hair) measurements may be a promising additional tool to monitor cumulative hydrocortisone replacement in AI.

  17. Mathematical model describing the thyroids-pituitary axis with distributed time delays in hormone transportation

    Science.gov (United States)

    Neamţu, Mihaela; Stoian, Dana; Navolan, Dan Bogdan

    2014-12-01

    In the present paper we provide a mathematical model that describe the hypothalamus-pituitary-thyroid axis in autoimmune (Hashimoto's) thyroiditis. Since there is a spatial separation between thyroid and pituitary gland in the body, time is needed for transportation of thyrotropin and thyroxine between the glands. Thus, the distributed time delays are considered as both weak and Dirac kernels. The delayed model is analyzed regarding the stability and bifurcation behavior. The last part contains some numerical simulations to illustrate the effectiveness of our results and conclusions.

  18. Electrotonic Coupling in the Pituitary Supports the Hypothalamic-Pituitary-Gonadal Axis in a Sex Specific Manner

    Directory of Open Access Journals (Sweden)

    Christina Göngrich

    2016-08-01

    Full Text Available Gap junctions are present in many cell types throughout the animal kingdom and allow fast intercellular electrical and chemical communication between neighboring cells. Connexin-36 (Cx36, the major neuronal gap junction protein, synchronizes cellular activity in the brain, but also in other organs. Here we identify a sex-specific role for Cx36 within the hypothalamic-pituitary-gonadal (HPG axis at the level of the anterior pituitary gland (AP. We show that Cx36 is expressed in gonadotropes of the AP sustaining their synchronous activity. Cx36 ablation affects the entire downstream HPG axis in females, but not in males. We demonstrate that Cx36-mediated coupling between gonadotropes in the AP supports gonadotropin-releasing hormone-induced secretion of luteinizing hormone. Furthermore, we provide evidence for negative feedback regulation of Cx36 expression in the AP by estradiol. We thus conclude that hormonally-controlled plasticity of gap junction communication at the level of the AP constitutes an additional mechanism affecting female reproduction.

  19. Exploration of the hypothalamic-pituitary-adrenal function as a tool to evaluate animal welfare.

    Science.gov (United States)

    Mormède, Pierre; Andanson, Stéphane; Aupérin, Benoit; Beerda, Bonne; Guémené, Daniel; Malmkvist, Jens; Manteca, Xavier; Manteuffel, Gerhard; Prunet, Patrick; van Reenen, Cornelis G; Richard, Sabine; Veissier, Isabelle

    2007-10-22

    Measuring HPA axis activity is the standard approach to the study of stress and welfare in farm animals. Although the reference technique is the use of blood plasma to measure glucocorticoid hormones (cortisol or corticosterone), several alternative methods such as the measurement of corticosteroids in saliva, urine or faeces have been developed to overcome the stress induced by blood sampling itself. In chronic stress situations, as is frequently the case in studies about farm animal welfare, hormonal secretions are usually unchanged but dynamic testing allows the demonstration of functional changes at several levels of the system, including the sensitization of the adrenal cortex to ACTH and the resistance of the axis to feedback inhibition by corticosteroids (dexamethasone suppression test). Beyond these procedural aspects, the main pitfall in the use of HPA axis activity is in the interpretation of experimental data. The large variability of the system has to be taken into consideration, since corticosteroid hormone secretion is usually pulsatile, follows diurnal and seasonal rhythms, is influenced by feed intake and environmental factors such as temperature and humidity, age and physiological state, just to cite the main sources of variation. The corresponding changes reflect the important role of glucocorticoid hormones in a number of basic physiological processes such as energy metabolism and central nervous system functioning. Furthermore, large differences have been found across species, breeds and individuals, which reflect the contribution of genetic factors and environmental influences, especially during development, in HPA axis functioning. Usually, these results will be integrated with data from behavioral observation, production and pathology records in a comprehensive approach of farm animal welfare.

  20. Pituitary-thyroid axis in short- and long-term experimental diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Nascimento-Saba C.C.A.

    1997-01-01

    Full Text Available Short-term experimental diabetes mellitus (DM produces a significant decrease in serum thyroid hormones, a decreased or normal serum thyroid-stimulating hormone (TSH and a reduction in hepatic and renal T4-5'-deiodination. However, little is known about the effects of chronic diabetes mellitus on the pituitary-thyroid axis function. We evaluated the changes induced by very short-term (6 days, short-term (15 days and chronic (6 months streptozotocin-induced diabetes mellitus in 3-month old female Dutch-Miranda rat serum T4, serum TSH and T4-5'-deiodinase activity in the thyroid and pituitary glands. Serum hormones were determined by specific radioimmunoassays. Iodothyronine-5'-deiodinase activities were assayed in the thyroid and pituitary microsomal fractions using 2 µM T4 as substrate. Mean serum T4 was significantly decreased from 3.3 to 2.0 µg/dl 6 days after diabetes mellitus induction, and from 2.2 to 1.5 µg/dl after 15 days of DM, with no significant changes in serum TSH, indicating a decreased pituitary TSH responsiveness to the diminished suppression by T4, even though pituitary T4-5'-deiodinase activity was unchanged. Thyroid T4-5'-deiodinase was unchanged after 6 days of diabetes mellitus, but was significantly increased from 20.6 to 37.0 pmol T3/mg protein after 15 days. Six months after diabetes mellitus induction, both serum T4 and thyroid T4-5'-deiodinase returned to normal ranges and serum TSH was unchanged, although pituitary T4-5'-deiodinase was now significantly decreased from 2.7 to 1.7 pmol T3/mg protein. These findings indicate that some kind of adaptation to chronic insulinopenia may occur at the thyroid level, but this does not seem to be true for the pituitary

  1. Sex-specific prenatal stress effects on the rat reproductive axis and adrenal gland structure

    Science.gov (United States)

    George, Susan O; Hogg, Charis O; Lai, Yu-Ting; Brunton, Paula J

    2016-01-01

    Abstract Social stress during pregnancy has profound effects on offspring physiology. This study examined whether an ethologically relevant social stress during late pregnancy in rats alters the reproductive axis and adrenal gland structure in post-pubertal male and female offspring. Prenatally stressed (PNS) pregnant rats (n=9) were exposed to an unfamiliar lactating rat for 10 min/day from day 16 to 20 of pregnancy inclusive, whereas control pregnant rats (n=9) remained in their home cages. Gonads, adrenal glands and blood samples were obtained from one female and one male from each litter at 11 to 12-weeks of age. Anogenital distance was measured. There was no treatment effect on body, adrenal or gonad weight at 11–12 weeks. PNS did not affect the number of primordial, secondary or tertiary ovarian follicles, numbers of corpora lutea or ovarian FSH receptor expression. There was an indication that PNS females had more primary follicles and greater ovarian aromatase expression compared with control females (both P=0.09). PNS males had longer anogenital distances (0.01±0.0 cm/g vs 0.008±0.00 cm/g; P=0.007) and higher plasma FSH concentrations (0.05 ng/mL vs 0.006 ng/mL; s.e.d.=0.023; P=0.043) compared with control males. There were no treatment effects on the number of Sertoli cells or seminiferous tubules, seminiferous tubule area, plasma testosterone concentration or testis expression of aromatase, FSH receptor or androgen receptor. PNS did not affect adrenal size. These data suggest that the developing male reproductive axis is more sensitive to maternal stress and that PNS may enhance aspects of male reproductive development. PMID:27026714

  2. Effect of Camphor on Pituitary-Gonadal Hormonal Axis and Oogenesis in Adult Female Rats

    OpenAIRE

    Habibollah Johari; Amir Ashkan Mahjoor; Siyamak Fallahi; Hossein Kargar Jahromi; Maryam Abedini; Mohammad Ali Poor Danesh; Zahra Zamani

    2013-01-01

    Background & Objective: Camphor stimulates the nervous system and the circulatory system, reduces lactation, and prevents conception and embryo embedding. We investigated the effects of camphor on the pituitary-gonadal hormonal axis and concentration of steroidal hormones.   Materials & Methods: The parameters investigated were concentrations of LH, FSH, estrogen, progesterone, and testosterone. Forty adult female rats at a mean weight of 180 ± 20 grams were divided into five groups. Camphor ...

  3. Pituitary-Gonadal Axis Hormone and Semen Analysis in Narcotic Dependency

    Directory of Open Access Journals (Sweden)

    Raheleh Assaei

    2013-04-01

    Full Text Available Background: Drug abuse is associated with numerous complications including hormonal disorders of hypothalamic-pituitary-gonadal axis and spermatogenic disorders. We have compared the hormone concentration of pituitary-gonadal axis and the semen analysis in opioid-dependent and non-opioid-dependent men.Materials and Methods: In this case-control study, serum concentration of pituitary- gonadal axis hormones and semen analysis in 48 opioid-dependent men as eligible to participate in the study were compared with those in 12 non-dependent men.Results: Free testosterone concentration in all test groups was significantly less than that in control group. Furthermore, the concentration of Dihydrotestosterone (DHT and Dehydroepiandrosterone Sulfate (DHEAS in all test groups except those addicted to heroin was less than in those in control group. Concentrations of LH, FSH, prolactin, SHBG, progesterone and estradiol, normal and abnormal sperm count in test groups were significantly different from control group. However, in all test groups, sperm motility rate was less than control group. No significant relationship was found between the concentration of sex hormones and the status of sperms motility. Conclusion: Chronic use of opioids will affect testosterone hormone and sperm, and it will cause hypogonadism and impairment of sperm motility.

  4. The pituitary-Leydig cell axis before and after orchiectomy in patients with stage I testicular cancer

    DEFF Research Database (Denmark)

    Bandak, Mikkel; Aksglaede, Lise; Juul, Anders

    2011-01-01

    This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy.......This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy....

  5. The pituitary-Leydig cell axis before and after orchiectomy in patients with stage I testicular cancer

    DEFF Research Database (Denmark)

    Bandak, Mikkel; Aksglaede, Lise; Juul, Anders

    2011-01-01

    This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy.......This study investigates the pituitary-Leydig cell axis in patients with stage I testicular germ cell cancer (TGCC) followed with surveillance only, in order to evaluate the risk of Leydig cell dysfunction one year after orchiectomy....

  6. 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.

  7. Pituitary Volume Prospectively Predicts Internalizing Symptoms in Adolescence

    Science.gov (United States)

    Zipursky, Amy R.; Whittle, Sarah; Yucel, Murat; Lorenzetti, Valentina; Wood, Stephen J.; Lubman, Dan I.; Simmons, Julian G.; Allen, Nicholas B.

    2011-01-01

    Background: Early adolescence is a critical time for the development of both internalizing and externalizing disorders. We aimed to investigate whether pituitary volume, an index of hypothalamic-pituitary-adrenal (HPA) axis function, represents a vulnerability factor for the emergence of internalizing and externalizing symptoms during adolescence…

  8. Pituitary Volume Prospectively Predicts Internalizing Symptoms in Adolescence

    Science.gov (United States)

    Zipursky, Amy R.; Whittle, Sarah; Yucel, Murat; Lorenzetti, Valentina; Wood, Stephen J.; Lubman, Dan I.; Simmons, Julian G.; Allen, Nicholas B.

    2011-01-01

    Background: Early adolescence is a critical time for the development of both internalizing and externalizing disorders. We aimed to investigate whether pituitary volume, an index of hypothalamic-pituitary-adrenal (HPA) axis function, represents a vulnerability factor for the emergence of internalizing and externalizing symptoms during adolescence…

  9. Pituitary gland volume in patients with schizophrenia, subjects at ultra high-risk of developing psychosis and healthy controls

    DEFF Research Database (Denmark)

    Nordholm, Dorte; Krogh, Jesper; Mondelli, Valeria;

    2013-01-01

    A larger pituitary size is thought to reflect a greater activation of the hypothalamic-pituitary-adrenal (HPA) axis, which may be related to an increase in the number and size of corticotroph cells. Some studies, but not all, indicate that pituitary volume increases before or at the onset...

  10. Evaluation of adrenal function and hormone replacement in patients with pituitary adenoma after surgery%垂体瘤患者术后肾上腺功能与激素替代的评估

    Institute of Scientific and Technical Information of China (English)

    王琳; 李强

    2016-01-01

    Objective Surgical treatment is the first choice for treatment in pituitary adenomas except for prolactinomas�In part of patients after operation would occur hypopituitarism,which with acute adrenal crisis is the most serious, and chronic adrenal insufficiency is different degree affects the patient's quality of life�Therefore,it is very important to accurately assess the hypothalamic pituitary adrenal( HPA) axis in patients with pituitary adenoma�But there is still a lack of reliable methods for evaluating adrenal axis�We reviewed the harm of adrenal insufficiency,HPA axis evaluation method of the new progress and postoperative glucocorticoid replacement treatment of new ideas, cleared the importance of reassessment and regular follow⁃up and the development of individual programs.%手术是除泌乳素瘤外的垂体瘤的首选治疗方案,部分患者在术后可发生垂体功能减退,其中以急性肾上腺危象最为严重,而慢性肾上腺功能低下则不同程度的影响着患者的生活质量,因此术后对下丘脑⁃垂体⁃肾上腺( HPA)轴进行准确的评估对垂体瘤术后患者的合理治疗显得至关重要,但目前尚缺乏对肾上腺轴进行评估的可靠方法。本文综述了肾上腺功能低下的危害、HPA轴评估方法的新进展以及术后糖皮质激素替代治疗的新观念,明确了术后重新评估和定期随访以及制定个体化方案的重要性。

  11. Role of the orexin system on the hypothalamus-pituitary-thyroid axis

    Directory of Open Access Journals (Sweden)

    Antonietta Messina

    2016-08-01

    Full Text Available Hypocretin/orexin are two hypothalamic neuropeptides discovered in 1998. Since their discovery, they had been one of the most studied neuropeptide systems because of their projecting fields innervating various brain areas. The orexinergic system is tiedto sleep-wakefulness cycle, and narcolepsy is a consequence of their system hypofunction. Orexinergic system is also involved in many other autonomic functions such as feeding, thermoregulation, cardiovascular and neuroendocrine regulation. The main aim of this mini reviewis to investigate the relationship between orexin and thyroid system regulation. Although knowledge about the orexin system is evolving, its putative effects on Hypothalamic-pituitary-thyroid (HTP axis still appear unclear. We analyzed some studies about orexin control of HTP axis to better know the relationship between them. The studies we analyzed suggest an action of the Hypocretin/orexin tomodulate the thyroid regulation but the nature (excitatory or inhibitory of this possible interaction remain actually unclear and it need to be confirmed.

  12. The Hypothalamic-Pituitary-Thyroid Axis in Infants and Children: Protection from Radioiodines

    Directory of Open Access Journals (Sweden)

    Jeffrey Fisher

    2014-01-01

    Full Text Available Potassium iodide (KI is recommended as an emergency treatment for exposure to radioiodines, most commonly associated with nuclear detonation or mishaps at nuclear power plants. Protecting the thyroid gland of infants and children remains a priority because of increased incidence of thyroid cancer in the young exposed to radioiodines (such as 131I and 133I. There is a lack of clinical studies for KI and radioiodines in children or infants to draw definitive conclusions about the effectiveness and safety of KI administration in the young. In this paper, we compare functional aspects of the hypothalamic-pituitary-thyroid (HPT axis in the young and adults and review the limited studies of KI in children. The HPT axis in the infant and child is hyperactive and therefore will respond less effectively to KI treatment compared to adults. Research on the safety and efficacy of KI in infants and children is needed.

  13. Provocative stimulation of the hypothalamic-pituitary-testicular axis in men with spinal cord injury.

    Science.gov (United States)

    Bauman, W A; La Fountaine, M F; Cirnigliaro, C M; Kirshblum, S C; Spungen, A M

    2016-11-01

    Prospective study. To determine the integrity of the hypothalamic-pituitary-testicular axis in healthy men with spinal cord injury (SCI). Thirty healthy men with chronic SCI (37±10 years) and thirty-eight able-bodied (AB) controls (36±10 years) participated. Gonadotropin-releasing hormone (GnRH; 100 μg IV) was administered to determine gonadotropin release, and human chorionic gonadotropin (hCG; 4000 IU IM) was administered to determine testosterone (T) secretion. Responses to stimulation were categorized as 'responder' or 'non-responder' by clinical criteria. Single factor ANOVA with repeated measures was performed to identify group differences. The proportion of responders to pituitary GnRH stimulation was similar in the SCI group (22 subjects (73%) for the follicular-stimulating hormone (FSH) and 23 subjects (76%) for the luteinizing hormone (LH) to that of the AB group. The SCI-responder group had an increased FSH response after stimulation compared with the AB-responder group (Pstimulation than the AB-responder group (P=0.06). The peak FSH response was at 60 min and the peak LH response at 30 min, regardless of group designation. All groups had similar increases in serum T concentration to hCG stimulation. The pituitary response to stimulation in healthy men with SCI revealed an augmented FSH response; LH response only trended higher. The testicular response to provocative stimulation was similar in hypogonadal and eugondal subjects and in GnRH responders and non-responders. These findings suggest a lack of hypothalamic drive of pituitary gonadotropin release in healthy people with chronic SCI.

  14. Toxic effects of methoxychlor administered subcutaneously on the hypothalamic-pituitary-testicular axis in adult rats.

    Science.gov (United States)

    Lafuente, A; Cabaleiro, T; Caride, A; Esquifino, A I

    2008-05-01

    This study was undertaken to evaluate the effects of methoxychlor MTX at the hypothalamic-pituitary-testicular axis in adult male rats. This global objective comprises three major aims: (1) to analyze the possible differential MTX effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence; (2) to evaluate effects induced by MTX exposure on gonadotropins and testosterone; 93 to elucidate whether the regulatory interactions in the hypothalamic-pituitary-testicular axis are modified by this pesticide. Animals were administered subcutaneously 25mg/kg/day of MTX for 1 month. MTX increased norepinephrine and serotonin content in anterior hypothalamus (P < or = 0.05), but decreased serotonin concentration in posterior hypothalamus (P < or = 0.05). MTX diminished serotonin turnover in anterior hypothalamus (P < or = 0.01) and decreased plasma LH (P < or = 0.001) and testosterone (P < or = 0.05) levels but those of FSH remained unmodified. We can conclude that MTX exposure: (1) could exert differential effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence, being the anterior hypothalamus the most sensitive region to the pesticide; (2) could inhibit LH and testosterone secretion without changing FSH; (3) four potential pathways might be involved in MTX effects on testosterone secretion (changing LH secretion; modifying serotonin and norepinephrine at the hypothalamic level; alterating the direct neural pathway between brain and testes; and/or by a direct effect in testes).

  15. Chronic Heroin Dependence Leading to Adrenal Insufficiency

    Directory of Open Access Journals (Sweden)

    Gautam Das

    2014-01-01

    Full Text Available Opioids have been the mainstay for pain relief and palliation over a long period of time. They are commonly abused by drug addicts and such dependence usually imparts severe physiologic effects on multiple organ systems. The negative impact of opioids on the endocrine system is poorly understood and often underestimated. We describe a patient who developed severe suppression of the hypothalamic-pituitary adrenal (HPA axis leading to secondary adrenal insufficiency due to long standing abuse of opioids.

  16. Atrazine Exposure and Reproductive Dysfunction through the Hypothalamus-Pituitary-Gonadal (HPG Axis

    Directory of Open Access Journals (Sweden)

    Sara E. Wirbisky

    2015-11-01

    Full Text Available Endocrine disrupting chemicals (EDC are exogenous agents that alter endogenous hormone signaling pathways. These chemicals target the neuroendocrine system which is composed of organs throughout the body that work alongside the central nervous system to regulate biological processes. Of primary importance is the hypothalamic-pituitary-gonadal (HPG axis which is vital for maintaining proper reproductive function. Atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine is a pre-emergent herbicide used to prevent the growth of weeds on various crops. This herbicide is reported to widely contaminate potable water supplies everywhere it is applied. As such, the European Union banned the use of atrazine in 2004. Currently the United States Environmental Protection Agency regulates atrazine at 3 parts per billion (ppb; μg/L in drinking water, while the World Health Organization recently changed their drinking water guideline to 100 ppb. Atrazine is implicated to be an EDC that alters reproductive dysfunction by targeting the HPG axis. However, questions remain as to the human health risks associated with atrazine exposure with studies reporting mixed results on the ability of atrazine to alter the HPG axis. In this review, the current findings for atrazine’s effects on the HPG axis are examined in mammalian, anuran, and fish models and in epidemiological studies.

  17. Atrazine Exposure and Reproductive Dysfunction through the Hypothalamus-Pituitary-Gonadal (HPG) Axis

    Science.gov (United States)

    Wirbisky, Sara E.; Freeman, Jennifer L.

    2017-01-01

    Endocrine disrupting chemicals (EDC) are exogenous agents that alter endogenous hormone signaling pathways. These chemicals target the neuroendocrine system which is composed of organs throughout the body that work alongside the central nervous system to regulate biological processes. Of primary importance is the hypothalamic-pituitary-gonadal (HPG) axis which is vital for maintaining proper reproductive function. Atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) is a pre-emergent herbicide used to prevent the growth of weeds on various crops. This herbicide is reported to widely contaminate potable water supplies everywhere it is applied. As such, the European Union banned the use of atrazine in 2004. Currently the United States Environmental Protection Agency regulates atrazine at 3 parts per billion (ppb; μg/L) in drinking water, while the World Health Organization recently changed their drinking water guideline to 100 ppb. Atrazine is implicated to be an EDC that alters reproductive dysfunction by targeting the HPG axis. However, questions remain as to the human health risks associated with atrazine exposure with studies reporting mixed results on the ability of atrazine to alter the HPG axis. In this review, the current findings for atrazine’s effects on the HPG axis are examined in mammalian, anuran, and fish models and in epidemiological studies. PMID:28713818

  18. Family environment is associated with HPA-axis activity in adolescents : The TRAILS study

    NARCIS (Netherlands)

    Marsman, R.; Nederhof, E.; Rosmalen, J.G.; Oldehinkel, A.J.; Ormel, J.; Buitelaar, J.K.

    2012-01-01

    The purpose of the present study was to investigate the developmental programming part of the theory of biological sensitivity to context using family environmental factors and hypothalamus-pituitary-adrenal (HPA) axis functioning. Specifically, we investigated whether perceived parenting (Rejection

  19. A Computational Model of the Rainbow Trout Hypothalamus-Pituitary-Ovary-Liver Axis.

    Directory of Open Access Journals (Sweden)

    Kendall Gillies

    2016-04-01

    Full Text Available Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature, viable gametes. In recent years there has been rapid growth in understanding fish reproductive biology, which has been motivated in part by recognition of the potential effects that climate change, habitat destruction and contaminant exposure can have on natural and cultured fish populations. New approaches to understanding the impacts of these stressors are being developed that require a systems biology approach with more biologically accurate and detailed mathematical models. We have developed a multi-scale mathematical model of the female rainbow trout hypothalamus-pituitary-ovary-liver axis to use as a tool to help understand the functioning of the system and for extrapolation of laboratory findings of stressor impacts on specific components of the axis. The model describes the essential endocrine components of the female rainbow trout reproductive axis. The model also describes the stage specific growth of maturing oocytes within the ovary and permits the presence of sub-populations of oocytes at different stages of development. Model formulation and parametrization was largely based on previously published in vivo and in vitro data in rainbow trout and new data on the synthesis of gonadotropins in the pituitary. Model predictions were validated against several previously published data sets for annual changes in gonadotropins and estradiol in rainbow trout. Estimates of select model parameters can be obtained from in vitro assays using either quantitative (direct estimation of rate constants or qualitative (relative change from control values approaches. This is an important aspect of mathematical models as in vitro, cell-based assays are expected to provide the bulk of experimental data for future risk assessments and will require quantitative physiological models to extrapolate across

  20. A Role for Glucocorticoids in Stress-Impaired Reproduction: Beyond the Hypothalamus and Pituitary

    OpenAIRE

    Whirledge, Shannon; Cidlowski, John A.

    2013-01-01

    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that oth...

  1. Hypothalamic-pituitary-thyroid axis hormones stimulate mitochondrial function and biogenesis in human hair follicles.

    Science.gov (United States)

    Vidali, Silvia; Knuever, Jana; Lerchner, Johannes; Giesen, Melanie; Bíró, Tamás; Klinger, Matthias; Kofler, Barbara; Funk, Wolfgang; Poeggeler, Burkhard; Paus, Ralf

    2014-01-01

    Thyroid hormones regulate mitochondrial function. As other hypothalamic-pituitary-thyroid (HPT) axis hormones, i.e., thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), are expressed in human hair follicles (HFs) and regulate mitochondrial function in human epidermis, we investigated in organ-cultured human scalp HFs whether TRH (30 nM), TSH (10 mU ml(-1)), thyroxine (T4) (100 nM), and triiodothyronine (T3) (100 pM) alter intrafollicular mitochondrial energy metabolism. All HPT-axis members increased gene and protein expression of mitochondrial-encoded subunit 1 of cytochrome c oxidase (MTCO1), a subunit of respiratory chain complex IV, mitochondrial transcription factor A (TFAM), and Porin. All hormones also stimulated intrafollicular complex I/IV activity and mitochondrial biogenesis. The TSH effects on MTCO1, TFAM, and porin could be abolished by K1-70, a TSH-receptor antagonist, suggesting a TSH receptor-mediated action. Notably, as measured by calorimetry, T3 and TSH increased follicular heat production, whereas T3/T4 and TRH stimulated ATP production in cultured HF keratinocytes. HPT-axis hormones did not increase reactive oxygen species (ROS) production. Rather, T3 and T4 reduced ROS formation, and all tested HPT-axis hormones increased the transcription of ROS scavengers (catalase, superoxide dismutase 2) in HF keratinocytes. Thus, mitochondrial biology, energy metabolism, and redox state of human HFs are subject to profound (neuro-)endocrine regulation by HPT-axis hormones. The neuroendocrine control of mitochondrial biology in a complex human mini-organ revealed here may be therapeutically exploitable.

  2. Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome.

    Science.gov (United States)

    Prete, Alessandro; Paragliola, Rosa Maria; Bottiglieri, Filomena; Rota, Carlo Antonio; Pontecorvi, Alfredo; Salvatori, Roberto; Corsello, Salvatore Maria

    2017-03-01

    Successful treatment of Cushing syndrome causes transient or permanent adrenal insufficiency deriving from endogenous hypercortisolism-induced hypothalamus-pituitary-adrenal-axis suppression. We analyzed pre-treatment factors potentially affecting the duration of adrenal insufficiency. We conducted a retrospective analysis on patients successfully treated for Cushing disease (15 patients) who underwent transsphenoidal surgery, and nonmalignant primary adrenal Cushing syndrome (31 patients) who underwent unilateral adrenalectomy, divided into patients with overt primary adrenal Cushing syndrome (14 patients) and subclinical primary adrenal Cushing syndrome (17 patients). Epidemiological data, medical history, and hormonal parameters depending on the etiology of hypercortisolism were collected and compared to the duration of adrenal insufficiency. The median duration of follow-up after surgery for Cushing disease and primary adrenal Cushing syndrome was 70 and 48 months, respectively. In the Cushing disease group, the median duration of adrenal insufficiency after transsphenoidal surgery was 15 months: younger age at diagnosis and longer duration of signs and symptoms of hypercortisolism before diagnosis and surgery were associated with longer duration of adrenal insufficiency. The median duration of adrenal insufficiency was 6 months for subclinical primary adrenal Cushing syndrome and 18.5 months for overt primary adrenal Cushing syndrome. The biochemical severity of hypercortisolism, the grade of hypothalamus-pituitary-adrenal-axis suppression, and treatment with ketoconazole before surgery accounted for longer duration of adrenal insufficiency. In patients with Cushing disease, younger age and delayed diagnosis and treatment predict longer need for glucocorticoid replacement therapy after successful transsphenoidal surgery. In patients with primary adrenal Cushing syndrome, the severity of hypercortisolism plays a primary role in influencing the duration of

  3. Effects of Methamphetamine on Pituitary Gonadal Axis and Spermatogenesis in Mature Male Rats

    Directory of Open Access Journals (Sweden)

    Malihe Heidari-Rarani

    2014-12-01

    Full Text Available Background: The use of methamphetamine has been significantly increased among youth in the last decade. Methamphetamine stimulates the central nervous system and affects on the body tissues and neurotransmitters like dopamine. In this study, the effect of methamphetamine as a medicine of amphetamine group is investigated on the pituitary-gonad axis and spermatogenesis. Materials and Methods: In this experimental study, 40 mature rats with 150±10 g weight are divided into in 4 groups including 10 rats in each group. Methamphetamine powder was weighted and it was solved in the normal saline to prepare a standard solution. Three experimental groups were injected in dosage 1, 3, 5 mg/kg using insulin syringe for 14 days, every day. Then, FSH, LH and testosterone concentrations were measured from the blood samples. The testis tissue was removed and after sectioning and staining by Hematoxylin-Eosin, was inspected by optical microscope for any changes. The average values of hormones and number of seminiferous cells were analyzed in SPSS-18 software using Duncan-test. Results: Experimental results showed that by increasing the concentration of methamphetamine, the serum level of LH and testosterone increase. While the FSH concentration decrease by increasing the level of methamphetamine. Also, investigation on the testis tissue showed that spermatogenesis has decreased on it in comparison to control group. This is because of methamphetamine effect on the gonads. Conclusion: The hormonal results and microscopic observations, it can conclude that using methamphetamine may cause destructive effects on pituitary-gonad axis and spermatogenesis and as a result, it may decrease fertility.

  4. Effect of warm-rearing and heat acclimation on pituitary-gonadal axis in male rats.

    Science.gov (United States)

    Kurowicka, B; Gajewska, A; Amarowicz, R; Kotwica, G

    2008-12-01

    Plasma gonadotrophic and testicular hormones concentrations in both immature and adult male rats exposed to 34 degrees C of ambient temperature were determined. In vitro steroidogenic ability of interstitial cells from experimental rats was also studied. Four groups of rats (n = 45) were used. Warm-reared (WR) males were housed in 34 degrees C and control-reared rats in 20 degrees C from birth to adulthood. The other groups were acclimated to 34 degrees C [warm-acclimated (WA) group] or 20 degrees C [deacclimated (DA) group] as adults. Decreased body weight and testis weight (p < 0.05) was found in heat-exposed groups, but relative testis weight was unchanged in WA and increased (p < 0.05) in WR and DA males. Plasma luteinizing hormone (LH) concentration increased in WA and DA males. Increased (p < 0.05) follicle-stimulating hormone (FSH) and prolactin plasma levels were found in DA and WR groups respectively. WA males had decreased testosterone (T) and WR rats androstenedione (A(4)) plasma concentration (p < 0.05). Interstitial cells (43% of them were Leydig cells by 3beta-hydroxysteroid dehydrogenase activity) from heat-exposed males secreted less (p < 0.05) T compared with the control group when incubated without LH (basal conditions). Androstenedione secretion decreased (p < 0.05) in WA rats. Secretion of estradiol-17beta (E(2)) was higher in WR and lower in DA cells under basal conditions. Weaker responsiveness to LH was observed in WR cells. Androgen synthesis from pregnenolone by interstitial cells increased (p < 0.05) in the WA group. We concluded that heat exposure of neonatal and adult male rats caused different pituitary-testicular axis adjustments. It seemed that long-term heat exposure of neonatal rats is less deleterious concerning the activity of pituitary-testicular axis than heat acclimation of adults.

  5. Hypothalamus-pituitary axis: an obligatory target for endocannabinoids to inhibit steroidogenesis in frog testis.

    Science.gov (United States)

    Chianese, Rosanna; Ciaramella, Vincenza; Fasano, Silvia; Pierantoni, Riccardo; Meccariello, Rosaria

    2014-09-01

    Endocannabinoids - primarily anandamide (AEA) and 2-arachidonoylglycerol (2-AG) - are lipophilic molecules that bind to cannabinoid receptors (CB1 and CB2). They affect neuroendocrine activity inhibiting gonadotropin releasing hormone (GnRH) secretion and testosterone production in rodents, through a molecular mechanism supposed to be hypothalamus dependent. In order to investigate such a role, we choose the seasonal breeder, the anuran amphibian Rana esculenta, an experimental model in which components of the endocannabinoid system have been characterized. In February, at the onset of a new spermatogenetic wave, we carried out in vitro incubations of frog testis with AEA, at 10(-9)M dose. Such a treatment had no effect on the expression of cytochrome P450 17alpha hydroxylase/17,20 lyase (cyp17) nor 3-β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase (3β-HSD), key enzymes of steroidogenesis. To understand whether or not the functionality of the hypothalamus-pituitary axis could be essential to support the role of endocannabinoids in steroidogenesis, frogs were injected with AEA, at 10(-8)M dose. Differently from in vitro experiment, the in vivo administration of AEA reduced the expression of cyp17 and 3β-HSD. Whereas the effect on 3β-HSD was counteracted by SR141716A (Rimonabant) - a selective antagonist of CB1, thus indicating a CB1 dependent modulation - the effect on cyp17 was not, suggesting a possible involvement of receptors other than CB1, probably the type-1 vanilloid receptor (TRPV1), since AEA works as an endocannabinoid and an endovanilloid as well. In conclusion our results indicate that endocannabinoids, via CB1, inhibit the expression of 3β-HSD in frog testis travelling along the hypothalamus-pituitary axis.

  6. The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin

    OpenAIRE

    2000-01-01

    Prolonged fasting is associated with a downregulation of the hypothalamo-pituitary thyroid (H-P-T) axis, which is reversed by administration of leptin. The hypothalamic melanocortin system regulates energy balance and mediates a number of central effects of leptin. In this study, we show that hypothalamic melanocortins can stimulate the thyroid axis and that their antagonist, agouti-related peptide (Agrp), can inhibit it. Intracerebroventricular (ICV) administration of Agrp (83-132) decreased...

  7. En masse resection of pancreas, spleen, celiac axis, stomach, kidney, adrenal, and colon for invasive pancreatic corpus and tail tumor.

    Science.gov (United States)

    Kutluturk, Koray; Alam, Abdul Hamid; Kayaalp, Cuneyt; Otan, Emrah; Aydin, Cemalettin

    2013-01-01

    Providing a more comfortable life and a longer survival for pancreatic corpus/tail tumors without metastasis depends on the complete resection. Recently, distal pancreatectomy with celiac axis resection was reported as a feasible and favorable method in selected pancreatic corpus/tail tumors which had invaded the celiac axis. Additional organ resections to the celiac axis were rarely required, and when necessary it was included only a single extra organ resection such as adrenal or intestine. Here, we described a distal pancreatic tumor invading most of the neighboring organs-stomach, celiac axis, left renal vein, left adrenal gland, and splenic flexure were treated by en bloc resection of all these organs. The patient was a 60-year-old man without any severe medical comorbidities. Postoperative course of the patient was uneventful, and he was discharged on postoperative day eight without any complication. Histopathology and stage of the tumor were adenocarcinoma and T4 N1 M0, respectively. Preoperative back pain of the patient was completely relieved in the postoperative period. As a result, celiac axis resection for pancreatic cancer is an extensive surgery, and a combined en masse resection of the invaded neighboring organs is a more extensive surgery than the celiac axis resection alone. This more extensive surgery is safe and feasible for selected patients with pancreatic cancer.

  8. En Masse Resection of Pancreas, Spleen, Celiac Axis, Stomach, Kidney, Adrenal, and Colon for Invasive Pancreatic Corpus and Tail Tumor

    Directory of Open Access Journals (Sweden)

    Koray Kutluturk

    2013-01-01

    Full Text Available Providing a more comfortable life and a longer survival for pancreatic corpus/tail tumors without metastasis depends on the complete resection. Recently, distal pancreatectomy with celiac axis resection was reported as a feasible and favorable method in selected pancreatic corpus/tail tumors which had invaded the celiac axis. Additional organ resections to the celiac axis were rarely required, and when necessary it was included only a single extra organ resection such as adrenal or intestine. Here, we described a distal pancreatic tumor invading most of the neighboring organs—stomach, celiac axis, left renal vein, left adrenal gland, and splenic flexure were treated by en bloc resection of all these organs. The patient was a 60-year-old man without any severe medical comorbidities. Postoperative course of the patient was uneventful, and he was discharged on postoperative day eight without any complication. Histopathology and stage of the tumor were adenocarcinoma and T4 N1 M0, respectively. Preoperative back pain of the patient was completely relieved in the postoperative period. As a result, celiac axis resection for pancreatic cancer is an extensive surgery, and a combined en masse resection of the invaded neighboring organs is a more extensive surgery than the celiac axis resection alone. This more extensive surgery is safe and feasible for selected patients with pancreatic cancer.

  9. Behavioral Abnormality Induced by Enhanced Hypothalamo-Pituitary-Adrenocortical Axis Activity under Dietary Zinc Deficiency and Its Usefulness as a Model

    Science.gov (United States)

    Takeda, Atsushi; Tamano, Haruna; Nishio, Ryusuke; Murakami, Taku

    2016-01-01

    Dietary zinc deficiency increases glucocorticoid secretion from the adrenal cortex via enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activity and induces neuropsychological symptoms, i.e., behavioral abnormality. Behavioral abnormality is due to the increase in glucocorticoid secretion rather than disturbance of brain zinc homeostasis, which occurs after the increase in glucocorticoid secretion. A major target of glucocorticoids is the hippocampus and their actions are often associated with disturbance of glutamatergic neurotransmission, which may be linked to behavioral abnormality, such as depressive symptoms and aggressive behavior under zinc deficiency. Glucocorticoid-mediated disturbance of glutamatergic neurotransmission in the hippocampus is also involved in the pathophysiology of, not only psychiatric disorders, such as depression, but also neurodegenerative disorders, e.g., Alzheimer’s disease. The evidence suggests that zinc-deficient animals are models for behavioral and psychological symptoms of dementia (BPSD), as well as depression. To understand validity to apply zinc-deficient animals as a behavioral abnormality model, this paper deals with the effect of antidepressive drugs and herbal medicines on hippocampal dysfunctions and behavioral abnormality, which are induced by enhanced HPA axis activity under dietary zinc deficiency. PMID:27438830

  10. Behavioral Abnormality Induced by Enhanced Hypothalamo-Pituitary-Adrenocortical Axis Activity under Dietary Zinc Deficiency and Its Usefulness as a Model

    Directory of Open Access Journals (Sweden)

    Atsushi Takeda

    2016-07-01

    Full Text Available Dietary zinc deficiency increases glucocorticoid secretion from the adrenal cortex via enhanced hypothalamo-pituitary-adrenocortical (HPA axis activity and induces neuropsychological symptoms, i.e., behavioral abnormality. Behavioral abnormality is due to the increase in glucocorticoid secretion rather than disturbance of brain zinc homeostasis, which occurs after the increase in glucocorticoid secretion. A major target of glucocorticoids is the hippocampus and their actions are often associated with disturbance of glutamatergic neurotransmission, which may be linked to behavioral abnormality, such as depressive symptoms and aggressive behavior under zinc deficiency. Glucocorticoid-mediated disturbance of glutamatergic neurotransmission in the hippocampus is also involved in the pathophysiology of, not only psychiatric disorders, such as depression, but also neurodegenerative disorders, e.g., Alzheimer’s disease. The evidence suggests that zinc-deficient animals are models for behavioral and psychological symptoms of dementia (BPSD, as well as depression. To understand validity to apply zinc-deficient animals as a behavioral abnormality model, this paper deals with the effect of antidepressive drugs and herbal medicines on hippocampal dysfunctions and behavioral abnormality, which are induced by enhanced HPA axis activity under dietary zinc deficiency.

  11. Testicular adrenal rest tumors in adult males with congenital adrenal hyperplasia: evaluation of pituitary-gonadal function before and after successful testis-sparing surgery in eight patients.

    NARCIS (Netherlands)

    Claahsen-van der Grinten, H.L.; Otten, B.J.; Takahashi, S.; Meuleman, E.J.H.; Hulsbergen- van de Kaa, C.A.; Sweep, C.G.J.; Hermus, A.R.M.M.

    2007-01-01

    CONTEXT: In male patients with congenital adrenal hyperplasia (CAH), testicular adrenal rest tumors (TART) are frequently present. These tumors can interfere with testicular function. Intensifying glucocorticoid therapy does not always lead to tumor regression and improvement of testicular function.

  12. Transcription factor 7-like 1 is involved in hypothalamo–pituitary axis development in mice and humans

    Science.gov (United States)

    Gaston-Massuet, Carles; McCabe, Mark J.; Scagliotti, Valeria; Young, Rodrigo M.; Carreno, Gabriela; Gregory, Louise C.; Jayakody, Sujatha A.; Pozzi, Sara; Gualtieri, Angelica; Basu, Basudha; Koniordou, Markela; Wu, Chun-I; Bancalari, Rodrigo E.; Rahikkala, Elisa; Veijola, Riitta; Lopponen, Tuija; Graziola, Federica; Turton, James; Signore, Massimo; Mousavy Gharavy, Seyedeh Neda; Charolidi, Nicoletta; Sokol, Sergei Y.; Merrill, Bradley J.; Dattani, Mehul T.; Martinez-Barbera, Juan Pedro

    2016-01-01

    Aberrant embryonic development of the hypothalamus and/or pituitary gland in humans results in congenital hypopituitarism (CH). Transcription factor 7-like 1 (TCF7L1), an important regulator of the WNT/β-catenin signaling pathway, is expressed in the developing forebrain and pituitary gland, but its role during hypothalamo–pituitary (HP) axis formation or involvement in human CH remains elusive. Using a conditional genetic approach in the mouse, we first demonstrate that TCF7L1 is required in the prospective hypothalamus to maintain normal expression of the hypothalamic signals involved in the induction and subsequent expansion of Rathke’s pouch progenitors. Next, we reveal that the function of TCF7L1 during HP axis development depends exclusively on the repressing activity of TCF7L1 and does not require its interaction with β-catenin. Finally, we report the identification of two independent missense variants in human TCF7L1, p.R92P and p.R400Q, in a cohort of patients with forebrain and/or pituitary defects. We demonstrate that these variants exhibit reduced repressing activity in vitro and in vivo relative to wild-type TCF7L1. Together, our data provide support for a conserved molecular function of TCF7L1 as a transcriptional repressor during HP axis development in mammals and identify variants in this transcription factor that are likely to contribute to the etiology of CH. PMID:26764381

  13. Hypothalamic-Pituitary-Adrenal Suppression and Iatrogenic Cushing's Syndrome as a Complication of Epidural Steroid Injections

    Directory of Open Access Journals (Sweden)

    Joyce Leary

    2013-01-01

    Full Text Available Epidural steroid injections are well accepted as a treatment for radicular back pain in appropriate candidates. While overall incidence of systemic side effects has not been well established, at least five biochemically proven cases of iatrogenic Cushing's Syndrome have been reported as complications of epidural steroid treatment. We present an additional case of iatrogenic Cushing's Syndrome and adrenal suppression in a middle-aged woman who received three epidural steroid injections over a four-month period. We review this case in the context of previous cases and discuss diagnostic and management issues.

  14. Effects of oral intoxication by lead acetate on pituitary-testicular axis in the pubertal rat

    Directory of Open Access Journals (Sweden)

    Hachfi Lamia

    2008-12-01

    Full Text Available

    Background: The aim of this work is to study the effects of lead on pituitary-testicular axis. It is about a direct toxicity on testicular cells or an indirect toxicity via abnormalities of the hypothalamic-pituitary axis?

    Methods: Forty male rats were divided equitably into four groups. One of these groups received tap water containing 0.3% lead acetate for one month. A second group was assigned to the same protocol but the intoxication was conducted for two months. The third and the fourth groups were used as reference. At the end of the experiment, the rats were anaesthetized and blood was collected for the proportioning of the FSH, the LH, testosterone and lead. The testes and epididymides were removed quickly and weighed. For the determination of testosterone in testicular fluids, a cruciate incision was made in the tunica albuginea of each right testis and centrifuged at 54xg for the extraction of interstitial fluid. Thereafter, the seminiferous tubules were extruded and centrifuged at 6000xg to collect seminiferous tubule fluid. The left testis of each animal was cut in two halves, one half was used for the histological examination and the other was suitably treated for the determination of the lead concentration. The epididymides were homogenized in solution containing Triton X-100 and spermatozoa were counted using Malessez cells. The plasma FSH and LH were determined by RIA using reagents from a commercial kit (BioInternational, France, while testosterone was determined by electrochemiluminescence (Elecsys, rochediagnostics. The lead concentration in blood and Tissues was measured by flameless atomic absorption spectrophotometry with the Zeeman effect background (Hitachi Z- 9000.

    Results: In the rats poisoned for one month, no notable effect was noted in spite of a blood lead concentration of 0.721 μg/ml. On the contrary, in animals exposed to lead acetate for two

  15. Hypothalamic-pituitary-adrenal axis function in survivors of childhood acute lymphoblastic leukemia and healthy controls.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Bierings, M.B.; Hoogerbrugge, P.M.; Ven, P.M. van de; Heijnen, C.J.; Kaspers, G.J.L.

    2012-01-01

    Of all malignancies in children, acute lymphoblastic leukemia (ALL) is the most common type. Since survival significantly improves over time, treatment-related side effects become increasingly important. Glucocorticoids play an important role in the treatment of ALL, but they may suppress the hypoth

  16. Dopamine receptor expression and function in the normal and pathological hypothalamus-pituitary-adrenal axis

    NARCIS (Netherlands)

    R. Pivonello (Rosario)

    2005-01-01

    markdownabstract__Abstract__ Dopamine is the predominant catecholamine neurotransmitter in the human central nervous system, where it controls a variety of functions including cognition, emotion, locomotor activity, food intake and endocrine regulation. Dopamine also plays multiple roles in

  17. Ghrelin's Role in the Hypothalamic-Pituitary-Adrenal Axis Stress Response: Implications for Mood Disorders

    NARCIS (Netherlands)

    Spencer, S.J.; Emmerzaal, T.L.; Kozicz, L.T.; Andrews, Z.B.

    2015-01-01

    Ghrelin is a stomach hormone normally associated with feeding behavior and energy homeostasis. Recent studies highlight that ghrelin targets the brain to regulate a diverse number of functions, including learning, memory, motivation, stress responses, anxiety, and mood. In this review, we discuss re

  18. Escitalopram prolonged fear induced by simulated public speaking and released hypothalamic-pituitary-adrenal axis activation.

    Science.gov (United States)

    Garcia-Leal, C; Del-Ben, C M; Leal, F M; Graeff, F G; Guimarães, F S

    2010-05-01

    Simulated public speaking (SPS) test is sensitive to drugs that interfere with serotonin-mediated neurotransmission and is supposed to recruit neural systems involved in panic disorder. The study was aimed at evaluating the effects of escitalopram, the most selective serotonin-selective reuptake inhibitor available, in SPS. Healthy males received, in a double-blind, randomized design, placebo (n = 12), 10 (n = 17) or 20 (n = 14) mg of escitalopram 2 hours before the test. Behavioural, autonomic and neuroendocrine measures were assessed. Both doses of escitalopram did not produce any effect before or during the speech but prolonged the fear induced by SPS. The test itself did not significantly change cortisol and prolactin levels but under the higher dose of escitalopram, cortisol and prolactin increased immediately after SPS. This fear-enhancing effect of escitalopram agrees with previously reported results with less selective serotonin reuptake inhibitors and the receptor antagonist ritanserin, indicating that serotonin inhibits the fear of speaking in public.

  19. Does the panic attack activate the hypothalamic-pituitary-adrenal axis?

    OpenAIRE

    Graeff Frederico G.; Garcia-Leal Cybele; Del-Ben Cristina M; Guimarães Francisco S.

    2005-01-01

    A bibliographic search has been performed in MEDLINE using cortisol and panic as key-words, occurring in the title and/or in the abstract. Human studies were selected, with no time limit. The following publications were excluded: reviewarticles, case reports, panic attacks in disorders other than panic disorder, and studies on changes that occurred in-between panic attacks. The results showed that real-life panic attacks as well as those induced by selective panicogenic agents such as lactate...

  20. The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia.

    LENUS (Irish Health Repository)

    O'Connor, T M

    2012-02-03

    Organisms survive by maintaining equilibrium with their environment. The stress system is critical to this homeostasis. Glucocorticoids modulate the stress response at a molecular level by altering gene expression, transcription, and translation, among other pathways. The effect is the inhibition of the functions of inflammatory cells, predominantly mediated through inhibition of cytokines, such as IL-1, IL-6, and TNF-alpha. The central effectors of the stress response are the corticotrophin-releasing hormone (CRH) and locus coeruleus-norepinephrine (LC-NE)\\/sympathetic systems. The CRH system activates the stress response and is subject to modulation by cytokines, hormones, and neurotransmitters. Glucocorticoids also modulate the growth, reproductive and thyroid axes. Abnormalities of stress system activation have been shown in inflammatory diseases such as rheumatoid arthritis, as well as behavioural syndromes such as melancholic depression. These disorders are comparable to those seen in rats whose CRH system is genetically abnormal. Thus, the stress response is central to resistance to inflammatory and behavioural syndromes. In this review, we describe the response to stress at molecular, cellular, neuroendocrine and behavioural levels, and discuss the disease processes that result from a dysregulation of this response, as well as recent developments in their treatment.

  1. Hypothalamic-Pituitary-Adrenal Axis Physiology and Cognitive Control of Behavior in Stress Inoculated Monkeys

    Science.gov (United States)

    Parker, Karen J.; Buckmaster, Christine L.; Lindley, Steven E.; Schatzberg, Alan F.; Lyons, David M.

    2012-01-01

    Monkeys exposed to stress inoculation protocols early in life subsequently exhibit diminished neurobiological responses to moderate psychological stressors and enhanced cognitive control of behavior during juvenile development compared to non-inoculated monkeys. The present experiments extended these findings and revealed that stress inoculated…

  2. Maternal Influences on Epigenetic Programming of the Developing Hypothalamic-Pituitary-Adrenal Axis

    Science.gov (United States)

    Parental and environmental factors during the prenatal and postnatal periods permanently affect the physiology and metabolism of offspring, potentially increasing risk of disease later in life. Underlying mechanisms are beginning to be elucidated, and effects on a number of organ...

  3. Sleep and Endocrinology: Hypothalamic-pituitary- adrenal axis and growth hormone

    Directory of Open Access Journals (Sweden)

    Ravinder Goswami

    2014-03-01

    Full Text Available The supra-chiasmatic nucleus (SCN is the primarily biological clock determining thecircadian rhythm. The neurons of the nucleus making this clock have inherent rhythmand set in biological day and night. These periods usually corresponds to day/night, andindirectly to sleep-wakefulness cycle, in most individuals. Retino-hypothalamic tractcarrying photic information from the retina provides the most important input tomaintain the inherent rhythm of the SCN. The rhythmic discharges from the SCN tovarious neurons of the central nervous system, including pineal gland andhypothalamus, translate into circadian rhythm characteristic of several hormones andmetabolites such as glucose. As a result there is a pattern of hormonal changesoccurring during cycle of sleep wakefulness. Most characteristic of these changes aresurge of melatonin with biological night, surge of growth hormone-releasing hormone(GHRHat onset of sleep and surge of corticotropin-releasinghormone(CRHduring late part of the sleep. The cause and effect relationship of the hypothalamicreleasing hormones and their target hormones on various phases of sleep includinginitial non rapid eye movement (NREM phase at onset of sleep, and rapid eyemovement (REM phase near awakening, is an upcoming research area. Sleepelectroencephalogram (EEG determining the onset of NREM and REM sleep is animportant tool complimenting the studies assessing relationship between varioushormones and phases of sleep. The slow wave activity (SWA corresponds to theintensity of sleep at its onset during the biological night of an individual. Besides,GHRH and CRH, several other peptide and steroid hormones such as growthhormone (GH, its secretagogues, ghrelin, neuropeptide Y, estrogen anddehydroepiandrosterone sulfate are associated or have the potential to change phases ofsleep including initial slow wave-NREM sleep.

  4. The role of oestradiol in sexually dimorphic hypothalamic-pituitary-adrena axis responses to intracerebroventricular ethanol administration in the rat.

    Science.gov (United States)

    Larkin, J W; Binks, S L; Li, Y; Selvage, D

    2010-01-01

    Systemic ethanol (EtOH) administration activates the hypothalamic-pituitary-adrenal (HPA) axis of rats in a sexually dimorphic manner. The present studies tested the role played by the central nervous system (CNS) in this phenomenon. To localise the effects of the drug to the brain, we utilised an experimental paradigm whereby a small, nontoxic amount of the drug was delivered via intracerebroventricular (i.c.v.) injection. EtoH administered i.c.v. rapidly diffuses throughout the cerebrospinal fluid and brain, and does not cause neuronal damage or have any long-term physiological or behavioural effects. Experimental groups included intact males, intact cycling females, and ovariectomised (OVX) animals with or without replacement oestradiol (E(2)). Intracerebroventricular EtOH-induced HPA hormonal activation was determined by measuring plasma adrenocorticotrophin (ACTH) levels. Activation of brain areas that both regulate HPA function and are responsive to gonadal hormones was determined using expression of the transcription factor c-fos (Fos) as a marker of neuronal activity. We observed sex- and oestrous cycle- dependent differences in HPA activation by EtOH as measured by both these parameters. ACTH secretion was highest in females in pro-oestrus or oestrus, just prior to or after the endogenous peak of E(2), as was Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and the locus coreuleus (LC) of the brainstem. In OVX animals, E(2) replacement caused an increase in PVN and LC Fos expression in response to i.c.v. EtOH compared to OVX controls, but a decrease in ACTH secretion. Taken together, these results indicate that at the level of the CNS, EtOH stimulates HPA activity more robustly at times when the effects of E(2) are high, but that E(2) alone is not responsible for this effect. The data further suggest that the LC plays an important role in the circuitry, which appears to be different from that activated following the systemic

  5. Analysis by immunocytochemistry and in situ hybridization of renin and its mRNA in kidney, testis, adrenal, and pituitary of the rat.

    Science.gov (United States)

    Deschepper, C F; Mellon, S H; Cumin, F; Baxter, J D; Ganong, W F

    1986-01-01

    Renin gene expression in cells and tissues of the rat was examined by in situ hybridization histochemistry and immunocytochemistry. By using a mouse cDNA probe, hybridization histochemistry revealed renin mRNA in the renal juxtaglomerular cells, testicular Leydig cells, adrenal zona glomerulosa cells, the intermediate lobe of the pituitary, and scattered cells of the anterior lobe of the pituitary. With four separate antisera to mouse submaxillary renin, there was immunoreactivity in the renal juxtaglomerular cells. However, only one of the antisera stained the Leydig cells, a second stained the adrenal zona glomerulosa, a third stained the intermediate lobe of the pituitary, and a fourth stained scattered cells of the anterior lobe of the pituitary that were identified as gonadotrophs. The variations with the different antisera in detecting extrarenal renin are unexplained but could imply that posttranslational proteolysis or glycosylation of preprorenin varies in different tissues with consequent variations in immunoreactivity. The finding of renin mRNA and renin-like immunoreactivity in these tissues supports the notion that these tissues are sites for production of renin. Images PMID:3532116

  6. Increased hypothalamic-pituitary-adrenal drive is associated with decreased appetite and hypoactivation of food-motivation neurocircuitry in anorexia nervosa.

    Science.gov (United States)

    Lawson, Elizabeth A; Holsen, Laura M; Desanti, Rebecca; Santin, McKale; Meenaghan, Erinne; Herzog, David B; Goldstein, Jill M; Klibanski, Anne

    2013-11-01

    Corticotrophin-releasing hormone (CRH)-mediated hypercortisolemia has been demonstrated in anorexia nervosa (AN), a psychiatric disorder characterized by food restriction despite low body weight. While CRH is anorexigenic, downstream cortisol stimulates hunger. Using a food-related functional magnetic resonance imaging (fMRI) paradigm, we have demonstrated hypoactivation of brain regions involved in food motivation in women with AN, even after weight recovery. The relationship between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and appetite and the association with food-motivation neurocircuitry hypoactivation are unknown in AN. We investigated the relationship between HPA activity, appetite, and food-motivation neurocircuitry hypoactivation in AN. Cross-sectional study of 36 women (13 AN, ten weight-recovered AN (ANWR), and 13 healthy controls (HC)). Peripheral cortisol and ACTH levels were measured in a fasting state and 30, 60, and 120 min after a standardized mixed meal. The visual analog scale was used to assess homeostatic and hedonic appetite. fMRI was performed during visual processing of food and non-food stimuli to measure the brain activation pre- and post-meal. In each group, serum cortisol levels decreased following the meal. Mean fasting, 120 min post-meal, and nadir cortisol levels were high in AN vs HC. Mean postprandial ACTH levels were high in ANWR compared with HC and AN subjects. Cortisol levels were associated with lower fasting homeostatic and hedonic appetite, independent of BMI and depressive symptoms. Cortisol levels were also associated with between-group variance in activation in the food-motivation brain regions (e.g. hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula). HPA activation may contribute to the maintenance of AN by the suppression of appetitive drive.

  7. An Unusual Case of Cushing’s Syndrome: Coexistence of Functional Pituitary and Adrenal Adenoma

    Directory of Open Access Journals (Sweden)

    Muzaffer İlhan

    2017-03-01

    Full Text Available A case of adrenocorticotropic hormone (ACTH-independent Cushing’s syndrome, which develops in the course of ACTH-dependent Cushing’s disease, is presented in this report. A 47-year-old woman with a past history of surgery and gamma knife radiosurgery because of Cushing’s disease was admitted to the endocrinology clinic with weight gain and unregulated blood glucose levels. Hypercortisolemia was still persisting and diagnostic work-up indicated ACTH-independent Cushing’s syndrome. Along with the rare possibility of this coexistence, longstanding ACTH hypersecretion can play a role in functional transition of adrenal adenomas. Further studies are needed to clarify the underlying mechanisms.

  8. Adipose tissue and adrenal glands: novel pathophysiological mechanisms and clinical applications.

    Science.gov (United States)

    Kargi, Atil Y; Iacobellis, Gianluca

    2014-01-01

    Hormones produced by the adrenal glands and adipose tissues have important roles in normal physiology and are altered in many disease states. Obesity is associated with changes in adrenal function, including increase in adrenal medullary catecholamine output, alterations of the hypothalamic-pituitary-adrenal (HPA) axis, elevations in circulating aldosterone together with changes in adipose tissue glucocorticoid metabolism, and enhanced adipocyte mineralocorticoid receptor activity. It is unknown whether these changes in adrenal endocrine function are in part responsible for the pathogenesis of obesity and related comorbidities or represent an adaptive response. In turn, adipose tissue hormones or "adipokines" have direct effects on the adrenal glands and interact with adrenal hormones at several levels. Here we review the emerging evidence supporting the existence of "cross talk" between the adrenal gland and adipose tissue, focusing on the relevance and roles of their respective hormones in health and disease states including obesity, metabolic syndrome, and primary disorders of the adrenals.

  9. A Review of the Phenomenon of Hysteresis in the Hypothalamus-Pituitary-Thyroid Axis.

    Science.gov (United States)

    Leow, Melvin Khee-Shing

    2016-01-01

    The existence of a phase of prolonged suppression of TSH despite normalization of serum thyroid hormones over a variable period of time during the recovery of thyrotoxicosis has been documented in literature. Conversely, a temporary elevation of TSH despite attainment of euthyroid levels of serum thyroid hormones following extreme hypothyroidism has also been observed. This rate-independent lag time in TSH recovery is an evidence of a "persistent memory" of the history of dysthyroid states the hypothalamus-pituitary-thyroid (HPT) axis has encountered after the thyroid hormone perturbations have faded out, a phenomenon termed "hysteresis." Notwithstanding its perplexing nature, hysteresis impacts upon the interpretation of thyroid function tests with sufficient regularity that clinicians risk misdiagnosing and implementing erroneous treatment out of ignorance of this aspect of thyrotropic biology. Mathematical modeling of this phenomenon is complicated but may allow the euthyroid set point to be predicted from thyroid function data exhibiting strong hysteresis effects. Such model predictions are potentially useful for clinical management. Although the molecular mechanisms mediating hysteresis remain elusive, epigenetics, such as histone modifications, are probably involved. However, attempts to reverse the process to hasten the resolution of the hysteretic process may not necessarily translate into improved physiology or optimal health benefits. This is not unexpected from teleological considerations, since hysteresis probably represents an adaptive endocrinological response with survival advantages evolutionarily conserved among vertebrates with a HPT system.

  10. Effect of Camphor on Pituitary-Gonadal Hormonal Axis and Oogenesis in Adult Female Rats

    Directory of Open Access Journals (Sweden)

    Habibollah Johari

    2013-06-01

    Full Text Available Background & Objective: Camphor stimulates the nervous system and the circulatory system, reduces lactation, and prevents conception and embryo embedding. We investigated the effects of camphor on the pituitary-gonadal hormonal axis and concentration of steroidal hormones.   Materials & Methods: The parameters investigated were concentrations of LH, FSH, estrogen, progesterone, and testosterone. Forty adult female rats at a mean weight of 180 ± 20 grams were divided into five groups. Camphor solution was prepared in olive oil at 25, 50, and 100 mg/kg doses, and 0.2 cc injections were done intraperitoneally every day for 2 weeks. The control group received no injection. The sham group received olive oil (as solvent of camphor and treatment groups of 1, 2, and 3 received doses of 25, 50, and 100 mg/kg. The treatment groups were sacrificed one day after the last injection, and their hearts were dissected and blood samples were obtained. The concentrations of the hormones were measured by the ELISA test, and the results were evaluated via the t-test, ANOVA, and Duncan.   Results: The results showed a significant decrease in the concentrations of testosterone and progesterone (p value < 0.05 and a significant increase in the concentrations of LH and FSH (p value <0.05.   Conclusion: Camphor augmented oogenesis via effecting a rise in the concentrations of LH and FSH in our rats.

  11. Sex-specific associations between sleep problems and hypothalamic-pituitary-adrenocortical axis activity in children.

    Science.gov (United States)

    Pesonen, Anu-Katriina; Kajantie, Eero; Heinonen, Kati; Pyhälä, Riikka; Lahti, Jari; Jones, Alexander; Matthews, Karen A; Eriksson, Johan G; Strandberg, Timo; Räikkönen, Katri

    2012-02-01

    Sleep problems are associated with reduced physical and mental health. Altered function of the hypothalamic-pituitary-adrenocortical axis (HPAA) may be one underlying mechanism. We studied the associations between sleep problems and HPAA activity in children. A cross-sectional epidemiological cohort study. Salivary cortisol was sampled throughout one day at home and during the Trier Social Stress Test for Children (TSST-C) in clinic. Sleep disorders were measured with a parent-rated Sleep Disturbance Scale for Children, and sleep duration measured by actigraphy for one week. 284 (51% girls) 8-year-old children. Boys with sleep problems (≥ 85 th percentile in any of the sleep-wake transition, arousal, excessive daytime somnolence or sleep hyperhydrosis subscales) had lower diurnal salivary cortisol levels and salivary cortisol responses to TSST-C stress in comparison to boys without sleep problems. Girls with sleep problems (≥ 85 th percentile in disorders of initiating and maintaining sleep) displayed a higher overall level of salivary cortisol during the TSST-C. Salivary cortisol responses to stress were lower in boys and higher in girls with more than one sleep problem. Sleep problems in children are associated with altered HPAA function, after controlling for actual sleep quantity measured by actigraphy. Boys with sleep problems had lower HPAA activity and girls with sleep problems had higher HPAA activity, compared to children without sleep problems. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Maternal prenatal licorice consumption alters hypothalamic-pituitary-adrenocortical axis function in children.

    Science.gov (United States)

    Räikkönen, Katri; Seckl, Jonathan R; Heinonen, Kati; Pyhälä, Riikka; Feldt, Kimmo; Jones, Alexander; Pesonen, Anu-Katriina; Phillips, David I W; Lahti, Jari; Järvenpää, Anna-Liisa; Eriksson, Johan G; Matthews, Karen A; Strandberg, Timo E; Kajantie, Eero

    2010-11-01

    Overexposure to glucocorticoids has been proposed as a mechanism by which prenatal adversity 'programs' the function of the hypothalamic-pituitary-adrenocortical axis (HPAA), thereby increasing the risk of adult diseases. Glycyrrhizin, a natural constituent of licorice, potently inhibits 11β-hydroxysteroid dehydrogenase type 2, the feto-placental barrier to the higher maternal cortisol levels. We studied if maternal consumption of glycyrrhizin in licorice associates with HPAA function in children. Diurnal salivary cortisol and salivary cortisol during the Trier Social Stress Test for Children (TSST-C) were measured in children (n=321, mean age=8.1, SD=0.3 years) whose mothers consumed varying levels of glycyrrhizin in licorice during pregnancy; exposure-level groups were labeled high (≥500 mg/week), moderate (250-499 mg/week) and zero-low (0-249 mg/week). In comparison to the zero-low exposure group, children in the high exposure group had 19.2% higher salivary cortisol awakening peak, 33.1% higher salivary cortisol awakening slope, 15.4% higher salivary cortisol awakening area under the curve (AUC), 30.8% higher baseline TSST-C salivary cortisol levels, and their salivary cortisol levels remained high throughout the TSST-C protocol (P-values HPAA function by overexposure to glucocorticoids. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Magnetic resonance imaging of hypothalamus hypophysis axis lesions; Relationship between posterior pituitary function and posterior bright spot

    Energy Technology Data Exchange (ETDEWEB)

    Shiina, Takeki; Uno, Kimiichi; Arimizu, Noboru; Yoshida, Sho (Chiba Univ. (Japan). School of Medicine); Yamada, Kenichi

    1990-04-01

    Magnetic resonance imaging (MRI) using a 0.5T superconductive machine was performed to the thirty three cases with a variety of the sellar and parasellar tumors and with dysfunction of the hypothalamus-hypophysis axis. Posterior pituitary bright spot (PBS) on T1 weighted image was evaluated with the pituitary hormonal function. These cases were 12 cases of post-treated tumors including pituitary adenoma (9 patients), suprasellar germinoma (2 patients) and craniopharyngioma (one patient), and non-tumorous conditions including 15 cases of central diabetes insipidus (DI), Syndrome of inappropriate secretion of ADH (SIADH) (one patient), Sheehan's syndrome (3 patients) and anorexia nervosa (2 patients). Pituitary bright spot was not seen in all 19 cases with overt DI. On the other hand, PBS was not seen in 9 cases without overt DI. Three cases of these 9 cases showing Sheehan's syndrome with insufficient antidiuretic hormone (ADH) secretion was considered as the state of subclinical DI. Posterior bright spot was not seen in all 13 cases of empty sella including partial empty sella. The results suggested that disappearance of PBS represents abnormality or loss of posterior pituitary function and also it was considered to be closely related to the empty sella. (author).

  14. The pituitary-thyroid axis set point in women is uninfluenced by X chromosome inactivation pattern? A twin study

    DEFF Research Database (Denmark)

    Brix, Thomas H; Hansen, Pia S; Kyvik, Kirsten O

    2010-01-01

    The pituitary-thyroid axis (PTA) set point is determined by a combination of genetic and environmental factors. However, despite considerable efforts to characterize the background, the causative genes as well as environmental factors are not well established. Theoretically, as shown for autoimmune...... thyroid disease, the pattern of X chromosome inactivation (XCI) could offer a novel explanation for the observed variability of the PTA set point in women....

  15. A Time-course Analysis of Effects of the Steroidogenesis Inhibitor Ketoconazole on Components of the Hypothalamic-pituitary-gonadal Axis of Fathead Minnows

    Science.gov (United States)

    The objective of this study was to evaluate temporal effects of the model steroidogenesis inhibitor ketoconazole (KTC) on aspects of reproductive endocrine function controlled by the hypothalamic-pituitary-gonadal (HPG) axis in the fathead minnow (Pimephales promelas). Ketoconazo...

  16. A time-course analysis of effects of the steroidogenesis inhibitor ketoconazole on components of the hypothalamic-pituitary-gonadal axis of fathead minnows (Presentation)

    Science.gov (United States)

    The objective of this study was to evaluate temporal effects of the model steroidogenesis inhibitor ketoconazole (KTC) on aspects of reproductive endocrine function controlled by the hypothalamic-pituitary-gonadal (HPG) axis in the fathead minnow (Pimephales promelas). Ketoconazo...

  17. The Effect of 8-Methoxypsoralen on Pituitary-Gonad Axis and Ovarian Function in Mice

    Directory of Open Access Journals (Sweden)

    Esmail Fattahi

    2013-01-01

    Full Text Available Objective: 8-Methoxypsoralen (8-MOP is a photoactive compound widely used in the treatment of proliferate disorders. The present study investigates the effects of 8-MOP on ovary function and pituitary-gonad axis in mice.Materials and Methods: In this experimental analytical study, 45 female Balb/C mice were divided into three groups (n=15, control, sham (olive oil injection and experimental. The experimental group were received an intraperitoneal (i.p. injection of the LD50 dose of 60 mg/kg 8-MOP. At 30 days after injection, the animals were sacrificed while in the proestrus stage and examined for morphological and histological changes their ovaries. Blood samples were collected and estrogen, luteinizing hormone (LH and follicle stimulating hormone (FSH levels were assessed by radioimmunoassay. Data were analyzed using one-way ANOVA and the t test.Results: The mean levels of estrogen and progesterone in the experimental group significantly decreased (p<0.001. However, there was a significant increase in LH and FSH levels in this group compared to the control groups (p<0.001. The mean number and diameter of the corpus luteum (CL and the number of growing follicles in the experimental group significantly reduced compared to the control and sham groups (p<0.001. The mean granulosa thickness in the experimental group also significantly decreased compared to the control and sham groups (p<0.001.Conclusion: Our data indicated that 8-MOP can affect the levels of LH, FSH, estrogen and progesterone. Our findings further suggest that consecutive doses of 8-MOP may impair the female reproductive tract (or development.

  18. Enhancing offspring hypothalamic-pituitary-adrenal (HPA) regulation via systematic novelty exposure: the influence of maternal HPA function.

    Science.gov (United States)

    Dinces, Sarah M; Romeo, Russell D; McEwen, Bruce S; Tang, Akaysha C

    2014-01-01

    In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother's ability to mount a rapid corticosterone (CORT) response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring hypothalamic-pituitary-adrenal (HPA) regulation. Using a 2 × 2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel) daily during infancy (PND 1-21) and the other half of the litter remained in the home cage (Neo_Home); we further exposed half of these two groups to early adulthood (PND 54-63) novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB) and the ability to mount a large rapid CORT response (CORTE) to the onset of an acute stressor. Assessment of adult offspring's ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring's ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the

  19. Embryo number and periconceptional undernutrition in the sheep have differential effects on adrenal epigenotype, growth, and development

    OpenAIRE

    Williams-Wyss, Olivia; Zhang, Song; MacLaughlin, Severence M.; Kleemann, David; Walker, Simon K.; Suter, Catherine M; Jennifer E Cropley; Janna L Morrison; Roberts, Claire T.; I. Caroline McMillen

    2014-01-01

    Exposure to poor maternal nutrition around the time of conception results in an early prepartum activation of the fetal pituitary-adrenal axis and in increased adrenal growth and stress response after birth associated with epigenetic changes in a differentially methylated region (DMR) of adrenal IGF2/H19. We have determined the effects of maternal undernutrition during the periconceptional period (PCUN: 70% of control intake from 60 days before until 6 days after conception) and early preimpl...

  20. Influence of streptozotocin-induced diabetes and insulin treatment on the pituitary-testicular axis during sexual maturation in rats.

    Science.gov (United States)

    Sudha, S; Valli, G; Julie, P M; Arunakaran, J; Govindarajulu, P; Balasubramanian, K

    2000-01-01

    Effects of streptozotocin (STZ)-diabetes and insulin treatment on the functioning of pituitary-testicular axis during sexual maturation was studied. Prepubertal (30 days old) and pubertal (50 days old) male Wistar rats were made diabetic by a single injection of STZ. A group of diabetic rats was given insulin (3U/100 g b.wt./day in 2 equally divided doses), 3 days after STZ treatment. Prepubertal and pubertal rats of all groups were killed on postnatal days 51 and 71, respectively. STZ-diabetes caused marked reduction in serum LH, FSH, prolactin, testosterone and testicular interstitial fluid testosterone as well as the activities of Leydig cellular steroidogenic enzymes (3beta-and 17beta-hydroxysteroid dehydrogenases). Insulin treatment to diabetic rats maintained these changes at control range except FSH and prolactin in prepubertal rats. The results indicate that (i) diabetes-induced steroidogenic lesions in Leydig cells represent a direct consequence of dysfunctioning of pituitary-testicular axis, (ii) the adverse effects of diabetes on pituitary-testicular functions are influenced by age of its induction and (iii) optimum insulin level is essential for the acquisition of Leydig cellular steroidogenic efficacy during sexual development.

  1. Pituitary-gonadal and pituitary-thyroid axis hormone concentrations before and during a hypoglycemic clamp after sleep deprivation in healthy men.

    Directory of Open Access Journals (Sweden)

    Kamila Jauch-Chara

    Full Text Available Total sleep deprivation (TSD exerts strong modulatory effects on the secretory activity of endocrine systems that might be related to TSD-induced challenges of cerebral glucose metabolism. Here, we investigate whether TSD affects the course of male pituitary-gonadal and pituitary-thyroid axis related hormones during a subsequent 240-min hypoglycemic clamp. Ten healthy men were tested on 2 different conditions, TSD and 7-hour regular sleep. Circulating concentrations of total testosterone, prolactin (PRL, thyroid stimulating hormone (TSH, free triiodothyronine (fT3, and free thyroxin (fT4 were measured during baseline and a subsequent hypoglycemic clamp taking place in the morning. Basal, i.e. at 07:00 am measured, concentrations of total testosterone (P = 0.05 and PRL (P<0.01 were lower while the values of TSH (P = 0.02, fT3 (P = 0.08, and fT4 (P = 0.04 were higher after TSD as compared to regular sleep. During the subsequent hypoglycemic clamp (all measurements from baseline to the end of the clamp analyzed total testosterone concentrations in the regular sleep (P<0.01 but not in the TSD condition (P = 0.61 decreased, while PRL levels increased (P = 0.05 irrespectively of the experimental condition (P = 0.31. TSH concentrations decreased during hypoglycemia (P<0.01, with this decrease being more pronounced after TSD (P = 0.04. However, at the end of the hypoglycemic clamp concentrations all of the above mentioned hormones did not differ between the two sleep conditions. Our data indicate a profound influence of TSD on male pituitary-gonadal and pituitary-thyroid axis hormones characterized by reduced basal testosterone and PRL levels and increased TSH levels. However, since concentrations of these hormones measured at the end of the 240-min hypoglycemic clamp were not affected by TSD it can be speculated that the influence of TSD on the two endocrine axes is rather short lived or does not interact in an additive

  2. Vitamin E-supplemented diets reduce lipid peroxidation but do not alter either pituitary-adrenal, glucose, and lactate responses to immobilization stress or gastric ulceration.

    Science.gov (United States)

    Armario, A; Campmany, L; Borras, M; Hidalgo, J

    1990-01-01

    It has been suggested that antioxidant administration to rats would reduce the physiological response to stress. In the present experiment adult male rats were given diets supplemented with vitamin E for one or seven days before they were subjected to immobilization stress. Vitamin E administration reduced hepatic and gastric lipid peroxidation in unstressed rats but did not modify the pituitary-adrenal, glucose and lactose responses to 1 or 18 h immobilization. Similarly, gastric ulceration caused by 18 h immobilization was unaffected by the diets. These results indicate that the inhibition of lipid peroxidation does not modify the response of several, well-known, stress-markers in the rat.

  3. 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...

  4. Effect of Selegiline on Pituitary- Gonad Axis and Spermatogenesis in Adult Male Rats

    Directory of Open Access Journals (Sweden)

    M. Mokhtari

    2005-04-01

    Full Text Available Selegiline is an inhibitor of B-Mono amino oxidase (MAO-B. In view of its usages in treatment of nervous illnesses such as Parkinson’s, Alzheimer’s and depression the side effects of selegiline on the endocrine axises are very important. In this research the effect of selegiline on pituitary- gonad axis and spermatogenesis in adult male rats were studied. For experimental and control groups 32 adult male rats from wistar race were divided into 4 groups of 8. The experimental groups (B,C,D were given oral doses of 5,10,15 (mg/kg.B.W selegiline for the period of 30 days and the control group (A received saline. The blood samples were taken 8 hour after receiving last dose at 30th day and the concentration of LH, FSH and testosterone was measured by RIA. In adition at the 30th day the testes were separated and histological changes was studied among experimental and control groups. The results were evaluated by using ANOVA and Duncan test. The statistical analysis of the results indicated that receiving different dosages of selegiline showed a significant increase in concentration of LH hormone in comparison with control group, but concentration of FSH did not show significant difference compared to the control group. In addition concentration of testosterone in response to different dosages in relative to the control group showed a significant decrease.According to the results we suggest that through LH increase, selegiline causes a decrease in concentration of testosterone via down-regulation receptors on leydig cells. Furthermore selegiline causes increase in dopamine concentration in striatum area as an inhibitor of MAO-B and intern causes decrease in concentration of prolactin. The decrease in prolactin secretion reduce the effect of LH hormone on leydig cell. In addition histological studies showed a significant effects caused by selegiline such as decreased number of spermatozoa in seminiferous tubules, leydig cells and reduced

  5. Regulatory effect of substance P on hypothalamus-pituitary-testes axis

    Institute of Scientific and Technical Information of China (English)

    Weihong Li; Enkui Jiang; Zhijie Chang

    2006-01-01

    BACKGROUND: Most of the studies about the regulation effect of substance P(SP)on reproductive axis involve female and few are about male.The effect of SP on the regulation of hypothalamus-pituitary-testes axis is unclear.OBJECTIVE: To observe the effect of SP on gonadotropin-releasing hormone (GnRH),luteinzing hormone (LH)and testosterone(T) in hypothalamus-adenohypophysis-testes cells.DESIGN: Controlled observation.SETTING: Department of Physiology and Deparment of Nuclear Liaoning Medical University.MATERIALS: Ten healthy male SD rats,of common grade,weighing from 230 to 250 g,were provided by the Experimental Animal Center of Liaoning Medical University.SP(Sigma,USA);LH and T radioimmunoassay kit (Nuclear Medical Technology Center of Tianjin Radiology Medical College);γ-immunology counter(state-run 262 Plant);all-purpose refrigerated centrifuge(DLL-4A,Dachang Medical Instrument Factory,Jiangsu).METHODS:This experiment was carried out in the Department of Physiology and Department of Nuclear Medicine,Liaoning Medical College in January 1997.The SD rats were raised at room temperature.One week later,hypothalamus tissue and adenohypophysis were separated.Abdominal cavity was cut open to take out bilateral testicles.The tegument was removed.The 3 kinds of tissues were cultured by cell culture technology separately. The cells of hypothalamus-adenohypophysis-testes were perflused with100 mg/L SP as follows:hypothalamus-adenohypophysis (the first group);hypothalamus (sp)-adenohypophysis (the second group);hypothalamus-adenohypophysis (sp) (the third group); adenohypophysis-testes (the fourth group);adenohypophysis-testes (sp)(the fifth group).The content of LH in adenopituicyte culture fluid and T in testes culture fluid were measured with radioimmunoassay.MAIN OUTCOME MEASURES:SP was perfused into the culture fluid of hypothalamus-adenohypophysis,then the content of LH in the adenopituicyte culture fluid and T in the testes culture fluid were measured.RESULTS:All the

  6. Participation of the pituitary-thyroid axis in the cardiovascular system in elderly patients with congestive heart failure.

    Science.gov (United States)

    Kimura, T; Kanda, T; Kuwabara, A; Shinohara, H; Kobayashi, I

    1997-01-01

    The relationship between the pituitary-thyroid axis and the cardiovascular system in patients with congestive heart failure (CHF) remains unknown. Therefore, we attempted to determine serum levels of thyroid hormones in relation to plasma atrial natriuretic peptide (ANP) levels and left ventricular (LV) function in patients with CHF. The echocardiographic ejection fraction significantly correlated with the thyroid stimulating hormone (TSH) (p thyroid hormones may participate in regulatory mechanisms of the cardiovascular system and altered thyroid hormone metabolism, which was characterized by a euthyroid sick syndrome.

  7. Novel insights into adrenal insufficiency in childhood.

    Science.gov (United States)

    Levy-Shraga, Y; Pinhas-Hamiel, O

    2014-12-01

    Adrenal insufficiency (AI) is a rare disease in childhood and adolescence that results from disruption in the hypothalamic-pituitary-adrenal axis. Pediatricians should be familiar with this entity since acute adrenal crisis is a life-threatening condition that requires immediate treatment. In the early stages of AI, the clinical manifestations may be subtle and non-specific; thus, they are frequently unrecognized. The main therapeutic approach in all forms of adrenal insufficiency is glucocorticoid replacement; the dose should be titrated appropriately to avoid under or overtreatment. Patient and family education is particularly important, to enable adjustment of dosage replacement therapy during stress and to prevent crisis. This article summarizes the current knowledge of AI and provides new insights on its management in children.

  8. [Senescence of endocrine function with special reference to the hypothalamic-pituitary-gonadal axis in the rat (author's transl)].

    Science.gov (United States)

    Kawashima, S

    1977-12-20

    In the control theories, aging is under genetic and environmental control. Endocrine function plays an important role in this control system by mediating between the environmental influence and the presumptive "aging gene". Therefore, the intrinsic aging of the hypothalamus, such as the changes in sensitivity to feedback suppression or stimulation, may lead to homostatic failure and then age-related pathology. As the subject of study we have selected the senile changes in the hypothalamic-pituitary-ovarian axis in the rat of the Wistar strain. The cessation of estrous cycle and the onset of persistent estrus or repetitive pseudopregnancy usually take place as early as at the end of the first half of life in rats. In this paper the results of the following experiments are briefly dealt with: (i) reciprocal transplantation of ovaries between young and old rats (the term "old" designates here "incapable of reproduction"), (ii) comparison of LH and FSH binding abilities in the ovarian preparations, (iii) comparison of serum and pituitary concentrations of LH, FSH and prolactin and the modifications after ovariectomy or by the administration of pharmacological drugs, and (iv) the difference between young and old rats in intensity of dopamine fluorescence in the hypothalamus. The results of these experiments seem to point to the hypothalamic-pituitary part rather than more peripheral organs (ovaries) as being primarily responsible for the outcome of the senile changes in the female rat.

  9. 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.

  10. Regulation of the pituitary-thyroid axis in adulthood is not related to birth weight

    DEFF Research Database (Denmark)

    Nielsen, Morten Frost Munk; Petersen, Inge; Hegedüs, Laszlo

    2013-01-01

    Low birth weight has been linked with changes in thyroid function in adulthood, but it is unknown whether fetal programming or underlying genetic and environmental factors explains the association. We hypothesized that birth weight influences the pituitary-thyroid set point in adults.......Low birth weight has been linked with changes in thyroid function in adulthood, but it is unknown whether fetal programming or underlying genetic and environmental factors explains the association. We hypothesized that birth weight influences the pituitary-thyroid set point in adults....

  11. Pituitary volume in patients with panic disorder.

    Science.gov (United States)

    Kartalci, Sukru; Dogan, Metin; Unal, Suheyla; Ozcan, A Cemal; Ozdemir, Serdal; Atmaca, Murad

    2011-01-15

    Panic patients have many functional deficiencies in the hypothalamic-pituitary-adrenal (HPA) axis. Previous studies have shown changed pituitary gland volume in some psychiatric disorders that have functional deficiencies in the HPA axis. However, to date no study has evaluated the pituitary gland volume in patients with panic disorder (PD). We investigated the pituitary gland volume in patients with PD (n=27) and age- and sex-matched healthy controls (n=27), using 1.5-T magnetic resonance imaging in this study. Analysis showed that patients with PD had significantly smaller pituitary volume compared to healthy subjects. Patients with agoraphobia especially had a significantly smaller pituitary volume than patients without agoraphobia. There was a significant relationship between the pituitary volume and both the severity of symptoms and the illness duration in the patient group. The results show that patients with PD have reduced pituitary volume, which may reflect the functional abnormalities seen in this disorder. These findings may help us better understand the pathology of PD. Copyright © 2010 Elsevier Inc. All rights reserved.

  12. Alteration of the hypothalamic-pituitary-gonadal axis in estrogen- and androgen-treated adult male leopard frog, Rana pipiens

    Directory of Open Access Journals (Sweden)

    Jones Jeremy T

    2005-01-01

    Full Text Available Abstract Background Gonadal steroids, in particular 5 alpha-dihydrotestosterone (DHT and 17 beta-estradiol (E2, have been shown to feed back on the hypothalamic-pituitary-gonadal (HPG axis of the ranid frog. However, questions still remain on how DHT and E2 impact two of the less-studied components of the ranid HPG axis, the hypothalamus and the gonad, and if the feedback effects are consistently negative. Thus, the goal of the study was to examine the effects of DHT and E2 upon the HPG axis of the gonadally-intact, sexually mature male leopard frogs, Rana pipiens. Methods R. pipiens were implanted with silastic capsules containing either cholesterol (Ch, a control, DHT, or E2 for 10 or 30 days. At each time point, steroid-induced changes in hypothalamic GnRH and pituitary LH concentrations, circulating luteinizing hormone (LH, and testicular histology were examined. Results Frogs implanted with DHT or E2 for 10 days did not show significant alterations in the HPG axis. In contrast, frogs implanted with hormones for 30 days had significantly lower circulating LH (for both DHT and E2, decreased pituitary LH concentration (for E2 only, and disrupted spermatogenesis (for both DHT and E2. The disruption of spermatogenesis was qualitatively similar between DHT and E2, although the effects of E2 were consistently more potent. In both DHT and E2-treated animals, a marked loss of all pre-meiotic germ cells was observed, although the loss of secondary spermatogonia appeared to be the primary cause of disrupted spermatogenesis. Unexpectedly, the presence of post-meiotic germ cells was either unaffected or enhanced by DHT or E2 treatment. Conclusions Overall, these results showed that both DHT and E2 inhibited circulating LH and disrupted spermatogenesis progressively in a time-dependent manner, with the longer duration of treatment producing the more pronounced effects. Further, the feedback effects exerted by both steroid hormones upon the HPG axis were

  13. The effect of metformin on the hypothalamic-pituitary-thyroid axis in patients with type 2 diabetes and subclinical hyperthyroidism.

    Science.gov (United States)

    Krysiak, R; Szkrobka, W; Okopien, B

    2015-04-01

    In hypothyroid patients, metformin was found to reduce serum levels of TSH. No previous study investigated metformin action on hypothalamic-pituitary-thyroid axis in patients with hyperthyroidism. The aim of our study was to assess the effect of metformin treatment on thyroid function tests in patients with untreated subclinical hyperthyroidism. We studied 15 patients with low but detectable TSH levels (0.1-0.4 mIU/L) (group 1), 12 patients with suppressed TSH levels (less than 0.1 mIU/L) (group 2) and 15 euthyroid patients with a history of hyperthyroidism, who because of coexisting 2 diabetes were treated with metformin (2.55-3 g daily). Glucose homeostasis markers, as well as serum levels of TSH and total and free thyroxine and triiodothyronine levels were assessed at baseline and after 3 and 6 months of therapy. As expected, metformin reduced plasma glucose, insulin resistance and glycated hemoglobin. However, with the exception of an insignificant decrease in TSH levels after 3-month therapy in group 2, metformin therapy did not affect thyroid function tests. Our results indicate that metformin has a negligible effect on hypothalamic-pituitary-thyroid axis activity in type 2 diabetic patients with subclinical hyperthyroidism.

  14. The pituitary-gonadal axis in healthy female dogs and bitches with gynecological disorders

    NARCIS (Netherlands)

    Buijtels, J.J.C.W.M.|info:eu-repo/dai/nl/304830844

    2011-01-01

    The pituitary gland produces and secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in a pulsatile fashion, induced by pulses of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Different cells in the ovary are capable of secreting estradiol, testosterone and proges

  15. Inhibin : its role in the regulation of the pituitary-testis axis.

    NARCIS (Netherlands)

    A.M. Ultee-van Gessel (Annemarie)

    1988-01-01

    textabstractThe endocrine and exocrine functions of the male gonads, the testes, are regulated by gonadotrophic hormones which are secreted by the pituitary gland. Two separate gonadotrophic hormones have been recognized: luteinizing hormone (LH) which influences Leydig cell function, and follicle-s

  16. Activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis at midgestation by estrogen-induced changes in placental corticosteroid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Pepe, G.J.; Waddell, B.J.; Albrecht, E.D. (Eastern Virginia Medical School, Norfolk (USA))

    1990-12-01

    We have hypothesized that the change in placental cortisol (F)-cortisone (E) metabolism induced by estrogen late in gestation is important to activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis, culminating in the ontogenesis of de novo F secretion by the fetal adrenal. The present study tested this hypothesis in vivo by comparing the proportion of F in the fetus derived via maternal and fetal production on day 100 (n = 7; term = day 184) and day 165 (n = 4) in untreated baboons and on day 100 in baboons (n = 9) in which 50-mg pellets of androstenedione were implanted sc in the mother in increasing numbers (i.e. two on day 70, four on day 78, six on day 86, and eight on day 94) to increase placental estrogen production. Maternal, uterine, and umbilical venous samples were collected during constant maternal infusion (120 min) of (3H)F/(14C)E, endogenous and radiolabeled F/E content was determined, and corticosteroid dynamics were quantified. The MCR and peripheral interconversion of F and E as well as the production rate of F were unaltered in the mother. However, at midgestation, androstenedione increased (P less than 0.05) estrogen by 62% and altered transuterofeto placental F-E metabolism from preferential reduction of E to preferential oxidation of F, a pattern similar to that at term. In untreated baboons, on day 100 none of the F in the fetus was due to fetal production, whereas by day 165, 49 +/- 6% was of fetal origin. In animals treated with androstenedione at midgestation, 22 +/- 4% of fetal F was derived de novo within the fetus. Thus, production of F by the fetus was negligible on day 100, increased near term in association with an increase in transplacental oxidation of F to E, and was induced at midgestation in baboons in which placental F-E metabolism was altered by an increase in estrogen production.

  17. Effects of repeated ether stress on the hypothalamic-pituitary-testes axis in adult rats with special reference to inhibin secretion.

    Science.gov (United States)

    Tohei, A; Tomabechi, T; Mamada, M; Akai, M; Watanabe, G; Taya, K

    1997-05-01

    Effects of ether stress on the hypothalamo-hypophysial-gonadal axis in adult male rats were examined. To clarify the role of adrenal glucocorticoids in gonadal function, the effects of adrenalectomy and Dexamethasone treatment were also investigated. Ether stress increased the plasma concentrations of ACTH and corticosterone, but decreased the plasma concentrations of LH, FSH, inhibin and testosterone. The pituitary responsiveness to LH-RH for LH release and testicular responsiveness to the endogenous LH for testosterone release were maintained in stressed rats. Adrenalectomy caused an increase in the plasma concentrations of ACTH, but decreased the plasma concentrations of LH, FSH and testosterone. Dexamethasone treatment in adrenalectomized rats recovered the levels of plasma gonadotropins to control levels. The concentration of plasma inhibin did not change in adrenalectomized rats, but it was decreased compared to control rats by Dexamethasone treatment. Treatments of Dexamethasone in intact male rats resulted in a decline in plasma levels of testosterone and inhibin without a decrease in the levels of LH and FSH, indicating the direct effect of Dexamethasone on the testes. These results indicate that increased ACTH secretion in stressed rats is probably due to hypersecretion of CRH from the hypothalamus, which suppresses gonadotropin secretion via the inhibition of LH-RH. The decreased levels of testosterone may be caused by a stress-induced decrease in plasma LH concentrations and increased secretion of corticosterone in the ether stressed rats. The low levels of plasma inhibin in stressed rats was also probably due to the direct effect of corticosterone on the Sertoli cells.

  18. Patient specific modeling of the HPA axis related to clinical diagnosis of depression

    DEFF Research Database (Denmark)

    Bangsgaard, Elisabeth; Ottesen, Johnny T.

    2016-01-01

    A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is an endocrine system responsible for coping with stress and it is likely to be involved in depression. The dynamics of the system is studied and existence, uniqueness and positivity of the solution and the existence...

  19. Effortful Control and Parenting: Associations with HPA Axis Reactivity in Early Childhood

    Science.gov (United States)

    Kryski, Katie R.; Dougherty, Lea R.; Dyson, Margaret W.; Olino, Thomas M.; Laptook, Rebecca S.; Klein, Daniel N.; Hayden, Elizabeth P.

    2013-01-01

    While activation of the hypothalamic-pituitary-adrenal (HPA) axis is an adaptive response to stress, excessive HPA axis reactivity may be an important marker of childhood vulnerability to psychopathology. Parenting, including parent affect during parent-child interactions, may play an important role in shaping the developing HPA system; however,…

  20. Evaluation of adrenal function in patients with hypothalamic and pituitary disorders : comparison of serum cortisol, urinary free cortisol and the human-corticotrophin releasing hormone test with the insulin tolerance test

    NARCIS (Netherlands)

    Dullaart, RPF; Pasterkamp, SH; Beentjes, JAM; Sluiter, WJ

    1999-01-01

    OBJECTIVE This study aimed to evaluate the performance of screening tests (serum cortisol and 24-h urinary free cortisol) and the human-corticotrophin releasing hormone (h-CRH) test in the assessment of adrenal function in patients with hypothalamic-pituitary disorders. DESIGN Summary receiver opera

  1. Evaluation of adrenal function in patients with hypothalamic and pituitary disorders : comparison of serum cortisol, urinary free cortisol and the human-corticotrophin releasing hormone test with the insulin tolerance test

    NARCIS (Netherlands)

    Dullaart, RPF; Pasterkamp, SH; Beentjes, JAM; Sluiter, WJ

    1999-01-01

    OBJECTIVE This study aimed to evaluate the performance of screening tests (serum cortisol and 24-h urinary free cortisol) and the human-corticotrophin releasing hormone (h-CRH) test in the assessment of adrenal function in patients with hypothalamic-pituitary disorders. DESIGN Summary receiver opera

  2. The neonicotinoid pesticide imidacloprid and the dithiocarbamate fungicide mancozeb disrupt the pituitary-thyroid axis of a wildlife bird.

    Science.gov (United States)

    Pandey, Surya Prakash; Mohanty, Banalata

    2015-03-01

    Thyroid is an important homeostatic regulator of metabolic activities as well as endocrine mechanisms including those of reproduction. Present investigation elucidated the thyroid disrupting potential of a neonicotinoid imidacloprid and a dithiocarbamate mancozeb in a seasonally breeding wildlife bird, Red Munia (Amandava amandava) who is vulnerable to these two pesticides through diet (seed grains and small insects). Adult male birds were exposed to 0.5% LD50 mgkg(-1)bwd(-1) of both the pesticides through food for 30days during the preparatory and breeding phases. Weight, volume and histopathology of thyroid gland were distinctly altered. Disruption of thyroid follicles reflected in nucleus-to-cytoplasm ratio (N/C) in epithelial and stromal cells, epithelial cell hypertrophy and altered colloid volume. Impairment of thyroid axis was pesticide and phase specific as evident from the plasma levels of thyroid (T4 and T3) and pituitary (TSH) hormones. In preparatory phase, plasma TSH was increased in response to decrease of T4 on mancozeb exposure showing responsiveness of the hypothalamic-pituitary-thyroid (HPT) axis to feedback regulation. On imidacloprid exposure, however, plasma levels of both T4 and TSH were decreased indicating non-functioning of negative feedback mechanism. Increased plasma T3 in response to both the pesticides exposure might be due to synthesis from non-thyroidal source(s) in a compensatory response to decrease level of T4. In breeding phase, impairment of HPT axis was more pronounced as plasma T4, T3 and TSH were significantly decreased in response to both mancozeb and imidacloprid. Thus, low dose pesticide exposure could affect the thyroid homeostasis and reproduction.

  3. Early-life exposure to dimethoate-induced reproductive toxicity: evaluation of effects on pituitary-testicular axis of mice.

    Science.gov (United States)

    Verma, Ruchna; Mohanty, Banalata

    2009-12-01

    In utero and lactational exposure to organophosphate dimethoate exerted toxic impact on the reproductive system of male mice. Pregnant mice were exposed to 4, 8, and 16 mg/kg of the pesticide, the sublethal doses (2.5, 5, and 10% of Lethal Dose(50) [LD(50)]), via gavaging from gestation day (GD) 6 to postnatal day (PND) 21. The effects on the male reproductive system were evaluated at two stages: at prepubertal age (PND 22) and at the postpubertal age of PND 63. Gonadal inhibition was reflected in the significant reduction of weight and distinct histopathological alteration of testis and epididymis as well as in decreased sperm counts, which could be linked to hormonal imbalance caused by dimethoate interference of reproductive axis. Disruption of pituitary-testicular axis was shown in the weak immunointensity of luteinizing hormone (LH) cells, reduction in their size and number, and lowered plasma LH and testosterone levels as observed in the neonates exposed to two higher tested doses. In addition, the direct toxic impact of the pesticide on the testicular Leydig cells and inhibition of steroidogenesis could be suggested. Drastic reduction in the testosterone level (approximately 70%) was suggestive of this effect. The adverse effects were persisted in the young adult mice. Developmental toxicity was evident in the highest dose-exposed (10% LD(50)) group where GD length and stillbirths were significantly increased along with a decrease of body weight and anogenital distance of the fetus. Maternal exposure of pesticide during gestation and lactation periods thus adversely affected the pituitary-testicular axis of mice neonates, which further caused reproductive dysfunctioning of young adult mice.

  4. Positive Association Between Posterior Subgenual Cingulate and Pituitary Volumes in Psychotic Major Depression

    Directory of Open Access Journals (Sweden)

    Konstantina Vassilopoulou

    2015-03-01

    Full Text Available Posterior subgenual cingulate cortex has been consistently linked with the pathophysiology of major depression in both structural and functional brain imaging studies. Likewise, the hyperactivity of the hypothalamic-pituitary-adrenal axis in major depression is well established, especially in its psychotic subtype. Moreover, posterior subgenual cingulate cortex exerts an inhibitory effect on the hypothalamic-pituitary-adrenal axis. While studies show pituitary volume to be a valid marker of hypothalamic-pituitary-adrenal axis activity, none have investigated the volumetric relationships between posterior subgenual cingulate cortex and pituitary volume in subtypes of major depressive disorder, which was precisely the aim of our study. We hypothesized a differential volumetric relationship in psychotic depression. We assessed posterior subgenual cingulate and pituitary volume using Magnetic Resonance Imaging scanning and investigated their volumetric relationships in 39 patients with major depressive disorder (17 psychotic and 22 melancholic and 18 normal controls. We found strong positive correlations between both left and right posterior subgenual volumes and pituitary volume only in the psychotic depression group (left: rs=0.77, p<0.001, right: rs=0.67, p=0.003. These positive associations were confirmed by regression analyses controlling for patient’s age and type of medications. By contrast, no significant volumetric associations were detected in the groups of melancholic patients and normal controls. Our findings provide support to the hypothesis that posterior subgenual cingulate is differentially involved in the pathophysiology of psychotic symptoms in major depressive disorder.

  5. Population pharmacokinetic/pharmacodynamic modelling of the hypothalamic-pituitary-gonadal axis

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel

    2005-01-01

    variations in parameters, identifying complicated non-linear dynamic dependencies, and deconvolving the functional feedback relationships of the HPG axis. The developed mechanism-based model of the HPG axis consisted of four compartments where the secretion of readily releasable LH from a pool compartment...

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

    Science.gov (United States)

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

    2015-01-01

    Androgens take part in the regulation of puberty and promote growth and development. They play their biological role by binding to a specific androgen receptor (AR). The aim of this study was to evaluate the expression of AR mRNA and protein in the pituitary and adrenal glands, to localize AR protein in luteinizing hormone (LH)-producing pituitary and adrenocortical cells, to determine plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone and the concentrations of corticosterone, testosterone (T), androstenedione (A4) and oestradiol (E2) in the adrenal glands of male turkeys at the age of 4, 8, 12, 16, 20, 24 and 28weeks. The concentrations of hormones and the expression of AR varied during development. The expression of AR mRNA and protein in pituitary increased during the growth. The increase of AR mRNA levels in pituitary occurred earlier than increase of AR protein. The percentage of pituitary cells expressing ARs in the population of LH-secreting cells increased in week 20. It suggests that AR expression in LH-producing pituitary cells is determined by the phase of development. The drop in adrenal AR mRNA and protein expression was accompanied by an increase in the concentrations of adrenal androgens. Those results could point to the presence of a compensatory mechanism that enables turkeys to avoid the potentially detrimental effects of high androgen concentrations. Our results will expand our knowledge of the role of steroids in the development of the reproductive system of turkeys from the first month of age until maturity. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Impaired hypothalamic-pituitary-testicular axis activity, spermatogenesis, and sperm function promote infertility in males with lead poisoning.

    Science.gov (United States)

    Gandhi, Jason; Hernandez, Rafael J; Chen, Andrew; Smith, Noel L; Sheynkin, Yefim R; Joshi, Gargi; Khan, Sardar Ali

    2017-02-10

    Lead poisoning is a stealthy threat to human physiological systems as chronic exposure can remain asymptomatic for long periods of time before symptoms manifest. We presently review the biophysical mechanisms of lead poisoning that contribute to male infertility. Environmental and occupational exposure of lead may adversely affect the hypothalamic-pituitary-testicular axis, impairing the induction of spermatogenesis. Dysfunction at the reproductive axis, namely testosterone suppression, is most susceptible and irreversible during pubertal development. Lead poisoning also appears to directly impair the process of spermatogenesis itself as well as sperm function. Spermatogenesis issues may manifest as low sperm count and stem from reproductive axis dysfunction or testicular degeneration. Generation of excessive reactive oxygen species due to lead-associated oxidative stress can potentially affect sperm viability, motility, DNA fragmentation, membrane lipid peroxidation, capacitation, hyperactivation, acrosome reaction, and chemotaxis for sperm-oocyte fusion, all of which can contribute to deter fertilization. Reproductive toxicity has been tested through cross-sectional analysis studies in humans as well as in vivo and in vitro studies in animals.

  8. The hypothalamic-pituitary-thyroid (HPT) axis in birds and its role in bird development and reproduction.

    Science.gov (United States)

    McNabb, F M Anne

    2007-01-01

    This article reviews thyroid function and its hypothalamic-pituitary-thyroid (HPT) axis control in birds with emphasis on the similarities and differences in thyroid function compared to mammals and other vertebrate classes. Thyroid hormones are important in metabolism and the thermogenesis required for homeothermy in birds, as in mammals, the other homeothermic class of vertebrates. Thyroid hormones play important roles in development and growth in birds, as is the case for all vertebrate classes. The developmental effects of thyroid hormones in birds are presented in the context of differences in precocial and altricial patterns of development and growth with emphasis on oviparous development. The sections on thyroid hormone actions include discussion of effects on the development of a number of tissue types as well as on seasonal organismal processes and interactions of the thyroid axis with reproduction. The current picture of how environmental chemicals may disrupt avian thyroid function is relatively limited and is presented in the context of the assessment endpoints that have been used to date. These endpoints are categorized as thyroid and HPT axis endpoints versus target organ endpoints. The final section discusses two recommended assay protocols, the avian two-generation toxicity assay and the avian one-generation assay, and whether these protocols can evaluate thyroid disruption in birds.

  9. Lactational exposure to atypical antipsychotic drugs disrupts the pituitary-testicular axis in mice neonates during post-natal development.

    Science.gov (United States)

    Mishra, Akash C; Mohanty, Banalata

    2010-07-01

    Olanzapine (OLNZ) and risperidone (RISP), two widely prescribed drugs for post-partum psychosis, transfer through milk to the neonates. Hence, neonates are susceptible to their adverse side effects. In the present study, the pituitary-testicular axis of lactationally exposed mice neonates (PND 28) was examined to evaluate the reproductive adverse effects. Testicular histopathology, immunocytochemistry and morphometric analysis of pituitary PRL (prolactin) and LH (luteinizing hormone) cells and plasma hormonal (PRL, LH and testosterone) levels were the various end points studied. Significantly regressed testes, reduced seminiferous tubules with disrupted germ-cell alignment, spermatogonial exfoliation into the tubule lumens and sparse sperms in the lumens were observed. PRL-immunointensity and plasma levels were elevated, whereas immunoreactivity and plasma levels of LH were decreased. Plasma testosterone levels were also decreased. The hypogonadism thus observed might be mediated by drug-induced hyperprolactinemia, which further inhibited secretions of LH and testosterone. Age may be the factor which made the neonates vulnerable to the PRL elevation by OLNZ which otherwise causes transient elevation in adults and is considered safe. The adverse impact was persistent until adulthood with higher doses of both of the drugs as evident by the analysis of testicular weight, histology and hormonal profiles of post-pubertal mice (PND 63) lactationally exposed as neonates.

  10. Alterations along the Hypothalamic-Pituitary-Thyroid Axis of the Zebrafish (Danio rerio after Exposure to Propylthiouracil

    Directory of Open Access Journals (Sweden)

    Florian Schmidt

    2011-01-01

    Full Text Available In the past, various approaches have been developed to detect adverse effects of pollutants on the thyroid of vertebrates, most of these with special emphasis on the South African clawed frog, Xenopus laevis. Although fish are primarily affected by thyroid-disrupting chemicals, studies into alterations of the thyroid of fish are scarce. Therefore, effects of the reference compound propylthiouracil on histopathology of the thyroid axis were analyzed in a modified early life-stage test with zebrafish (Danio rerio exposed to propylthiouracil. The test substance induced dose-dependent alterations of thyroidal tissue concomitant with increases in the number of surrounding blood vessels. Despite this massive proliferation of the thyroid, zebrafish were not able to maintain thyroxin concentrations. The pituitary was affected displaying significant alterations in thyroid-stimulating hormone cell counts. Quantitative evaluation of pituitary surface areas revealed a dose-dependent increase of adenohypophyseal tissue. Distinct histopathological effects may contribute to a more easy identification and interpretation of alterations induced by thyroid-disrupting chemicals.

  11. Sexually dimorphic effects of NMDA receptor antagonism on brain-pituitary-gonad axis development in the platyfish

    Science.gov (United States)

    Flynn, Katherine M.; Miller, Shelly A.; Sower, Stacia A.; Schreibman, Martin P.

    2002-01-01

    The N-methyl-D-aspartate glutamate receptor (NMDAR) is found in hypothalamic nuclei involved in the regulation of reproduction in several species of mammals and fishes. NMDAR is believed to affect reproductive development and function by regulating gonadotropin releasing hormone (GnRH)-producing cells. These pathways are likely to be sexually dimorphic, as are several other neurotransmitter systems involved in reproductive function. In this report, male and female platyfish received intraperitoneal injections of 0, 5, 10, 20, 40 or 60 microg/g body wt. of the non-competitive NMDAR antagonist MK-801. Injections began at 6 weeks of age and continued thrice weekly until control animals reached puberty, as evidenced by anal fin maturation. The percent of pubescent animals was significantly affected by sex and treatment, with fewer MK-801-injected females in puberty than control females at each dose (PHistological analyses revealed typical immature gonads and pituitary glands in treated females, and typical mature morphology in control females and all males. Immunocytochemical distribution of the R1 subunit of the NMDAR within the brain-pituitary-gonad (BPG) axis was limited to GnRH-containing brain cells in all animals; however, NMDAR1 distribution was in an immature pattern in treated females and a mature pattern in all others. Neural concentrations of GnRH were unaffected by MK-801 treatment in both sexes. These data suggest that in the platyfish, NMDAR influence on reproductive development is sexually dimorphic and occurs at, or above, the level of GnRH-containing cells of the BPG axis.

  12. Chemoprotective role of quercetin in manganese-induced toxicity along the brain-pituitary-testicular axis in rats.

    Science.gov (United States)

    Adedara, Isaac A; Subair, Temitayo I; Ego, Valerie C; Oyediran, Oluwasetemi; Farombi, Ebenezer O

    2017-02-01

    Reproductive dysfunction in response to manganese exposure has been reported in humans and animals. Quercetin, a bioflavonoid widely distributed in fruits, vegetables and beverages has been shown to possess antioxidant, anti-inflammatory and anti-apoptotic activities in different experimental model systems. However, there is dearth of scientific information on the influence of quercetin on manganese-induced reproductive toxicity. This study was designed to evaluate the influence of quercetin on manganese-induced functional alterations along the brain-pituitary- testicular axis in rats. Manganese was administered alone at 15 mg/kg body weight or orally co-treated with quercetin at 10 and 20 mg/kg body weight for 45 consecutive days. Results indicated that quercetin co-treatment significantly (p manganese-induced elevation in biomarkers of oxidative stress whereas it increased antioxidant enzymes activities and glutathione level in the brain, testes and epididymis of the treated rats. Furthermore, quercetin mediated suppression of inflammatory indices and caspase-3 activity was accompanied by preservation of histo-architectures of the brain, testes and epididymis in manganese-treated rats. The significant reversal of manganese-induced decreases in reproductive hormones (i.e. luteinizing hormone, follicle-stimulating hormone and testosterone) and testicular activities of acid phosphatase, alkaline phosphatase and lactate dehydrogenase by quercetin was complemented by an increase in sperm quality and quantity in the treated rats. Collectively, quercetin modulated manganese-induced toxicity along the brain-pituitary-testicular axis in rats via its intrinsic antioxidant, anti-inflammatory and anti-apoptotic activities, and may thus represent a potential pharmacological agent against manganese-induced male reproductive deficits in humans.

  13. Effects of cysteamine on the hypothalamic-pituitary axis in the rat

    Energy Technology Data Exchange (ETDEWEB)

    McComb, D.J.; Cairns, P.D.; Kovacs, K.; Szabo, S.

    1985-06-01

    The effects of cysteamine (CSH) on hypothalamic concentrations of neuropeptides were reviewed and correlated with available information on changes in pituitary hormone content and circulating pituitary hormone levels. In our study, we found notable changes in the morphology of lactotropes from female Long-Evans rats treated for 7 days with CSH (300 mg/(kg X day) per os). Forming granules increased in number, and crinophagy, which is the augmented incorporation of these granules into lysosomes, was evident. Storage granules were reduced in number. These changes were not suppressed by simultaneous administration of 17 beta-estradiol (50 micrograms/day s.c.) for 7 days. CSH administration failed to prevent estrogen-induced lactotrope hyperplasia. Serum prolactin levels were unaffected by CSH treatment. The morphological changes in the adenohypophysis did not resemble those observed when rats were treated with bromocriptine. The rough endoplasmic reticulum luminal density was reduced in gonadotropes from intact CSH-treated rats after 1 wk. CSH treatment suppressed the development of castration cells and significantly reduced serum luteinizing hormone levels in ovariectomized rats. The morphological effects of CSH appeared to be confined to lactotropes and gonadotropes.

  14. Infertility and Reproductive Function in Patients with Congenital Adrenal Hyperplasia: Pathophysiology, Advances in Management, and Recent Outcomes.

    Science.gov (United States)

    Lekarev, Oksana; Lin-Su, Karen; Vogiatzi, Maria G

    2015-12-01

    Individuals with congenital adrenal hyperplasia have reduced fertility. However, reproductive outcomes have improved over the years. This review provides an update on the multiple pathologic processes that contribute to reduced fertility in both sexes, from alterations of the hypothalamic-pituitary-gonadal axis to the direct effect on gonadal function by elevated circulating adrenal androgens. In addition, elevated serum progesterone concentrations may hinder ovulation and embryo implantation in women, whereas in men testicular adrenal rest tumors can be a major cause of infertility. Suppression of adrenal androgen secretion represents the first line of therapy toward spontaneous conception in both sexes. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Influence of fetal growth velocity and smallness at birth on adrenal function in adolescence

    DEFF Research Database (Denmark)

    Beck Jensen, Rikke; vielwerth, Signe; Larsen, Torben;

    2011-01-01

    The hypothalamic-pituitary-adrenal axis is susceptible to programming during fetal development and may be linked to risk of disease later in life. In a former prospective study the cohort was divided into those born appropriate for gestational age (AGA) or small for gestational age (SGA; birth...

  16. Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide

    DEFF Research Database (Denmark)

    Skov, M; Main, K M; Sillesen, Ida Blok

    2002-01-01

    A recent case of iatrogenic Cushing's syndrome and complete suppression of the pituitary-adrenal-axis in a patient with cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis treated with itraconazole as an antifungal agent, and budesonide as an anti-inflammatory agent led to a systematic...

  17. Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide

    DEFF Research Database (Denmark)

    Skov, M; Main, K M; Sillesen, Ida Blok

    2002-01-01

    A recent case of iatrogenic Cushing's syndrome and complete suppression of the pituitary-adrenal-axis in a patient with cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis treated with itraconazole as an antifungal agent, and budesonide as an anti-inflammatory agent led to a systemat...

  18. Effects of gonadotropin-releasing hormone administration on the pituitary-gonadal axis in male and female dogs before and after gonadectomy

    NARCIS (Netherlands)

    De Gier, J.; Buijtels, J.J.C.W.M.; Albers-Wolthers, C.H.J.; Oei, C.H.Y.; Kooistra, H.S.; Okkens, A.C.

    2012-01-01

    GnRH-stimulation tests were performed in 14 female and 14 male client-owned dogs of several breeds, before and 4 to 5 mo after gonadectomy. The aim of the study was to obtain more insight into the pituitary-gonadal axis in intact and neutered dogs and to establish reference values. Basal plasma lute

  19. A rare case of type 1 diabetes mellitus with pituitary hypoplasia.

    Science.gov (United States)

    Pinto, Jostol; Sudeep, K; Venkatesha, B M

    2014-01-01

    Growth failure and pubertal abnormalities are not uncommon in chronic uncontrolled metabolic diseases like diabetes mellitus. We present a young girl with uncontrolled type 1 diabetes mellitus, who presented with short stature and primary amenorrhea, and on evaluation was found to have anterior pituitary hypoplasia. In addition to uncontrolled diabetes mellitus, she presented with early onset growth failure and lack of spontaneous secondary sexual characteristics. She had central hypothyroidism and inappropriately normal gonadotropin levels. However her serum cortisol levels were normal. MRI of the sellar-suprasellar region revealed a small anterior pituitary gland with thinning of the pituitary stalk consistent with pituitary hypoplasia. While uncontrolled type 1 diabetes itself may cause growth retardation and pubertal abnormalities, this girl had coexisting pituitary maldevelopment - a rare co-existence of two major illnesses of unrelated etiologies. The partial pituitary hormonal deficiency, which spared the hypothalamo-pituitary-adrenal axis, may be due to a transcription factor defect.

  20. Pigs fed saturated fat/cholesterol have a blunted hypothalamic-pituitary-adrenal function, are insulin resistant and have decreased expression of IRS-1, PGC1α and PPARα.

    Science.gov (United States)

    Lomax, Michael A; Karamanlidis, Georgios; Laws, John; Cremers, Stephanie G; Weinberg, Peter D; Clarke, Lynne

    2013-04-01

    The increasing incidence of insulin resistance has been linked to both increased intake of saturated fatty acids and disruption of the hypothalamic-pituitary-adrenal (HPA) axis. We tested the hypothesis that adding saturated fat/cholesterol to the diet of growing pigs would both disrupt HPA function and cause insulin resistance. Three-month-old pigs were fed either a control (13% energy from fat) or a high saturated fatty acid cholesterol (HSFC) diet (44% energy from fat; 2% cholesterol). After 10 weeks on the diets, intravenous ACTH, insulin and glucose challenges were performed, and after 12 weeks, tissue samples were taken for measurement of mRNA and for lipid-rich aortic lesions. Plasma total, HDL- and LDL-cholesterol were significantly increased in pigs fed the HSFC diet. Cortisol release during the ACTH challenge was suppressed in HSFC-fed pigs which were also more insulin resistant and glucose intolerant than controls. The HSFC diet decreased the expression of insulin receptor (IR) and insulin receptor substrate-1 in muscle and adipose tissue as well as adiponectin and adiponectin receptor 2 expression in fat. The HSFC diet decreased PGC-1α and PPARα expression in muscle but increased PPARα expression in liver. There was a trend for an increase in lipid-stained lesion frequency around the abdominal branches of the aorta in HSFC-fed pigs. We conclude that feeding increased saturated fat to pigs causes disruption in the HPA axis, insulin resistance and decreased muscle and adipose expression of genes controlling insulin signalling and mitochondrial oxidative capacity.

  1. Preliminary Study of Quercetin Affecting the Hypothalamic-Pituitary-Gonadal Axis on Rat Endometriosis Model

    Directory of Open Access Journals (Sweden)

    Yang Cao

    2014-01-01

    Full Text Available In this study, the endometriosis rats model was randomly divided into 6 groups: model control group, ovariectomized group, Gestrinone group, and quercetin high/medium/low dose group. Rats were killed after 3 weeks of administration. The expression levels of serum FSH and LH were detected by ELISA. The localizations and quantities of ERα, ERβ, and PR were detected by immunohistochemistry and western blot. The results showed that the mechanism of quercetin inhibiting the growth of ectopic endometrium on rat endometriosis model may be through the decreasing of serum FSH and LH levels and then reducing local estrogen content to make the ectopic endometrium atrophy. Quercetin can decrease the expression of ERα, ERβ, and PR in hypothalamus, pituitary, and endometrium, thereby inhibiting estrogen and progesterone binding to their receptors to play the role of antiestrogen and progesterone.

  2. Disorders of adrenal development.

    Science.gov (United States)

    Ferraz-de-Souza, Bruno; Achermann, John C

    2008-01-01

    Human adrenal development is a complex and relatively poorly understood process. However, significant insight into some of the mechanisms regulating adrenal development and function is being obtained through the analysis of individuals and families with adrenal hypoplasia. Adrenal hypoplasia can occur: (1) secondary to defects in pituitary adrenocorticotropin (ACTH) synthesis, processing and release (secondary adrenal hypoplasia; e.g. HESX1, LHX4, SOX3, TPIT, pituitary POMC, PC1); (2) as part of several ACTH resistance syndromes (e.g. MC2R/ACTHR, MRAP, Alacrima, Achalasia, Addison disease), or as (3) a primary defect in the development of the adrenal gland itself (primary adrenal hypoplasia; e.g. DAX1/NR0B1 - dosage-sensitive sex reversal, adrenal hypoplasia congenita critical region on the X chromosome 1). Indeed, the X-linked form of primary adrenal hypoplasia due to deletions or mutations in the orphan nuclear receptor DAX1 occurs in around half of male infants presenting with a salt-losing adrenal crisis, where no obvious steroidogenic defect (e.g. 21-hydroxylase deficiency), metabolic abnormality (e.g. neonatal adrenoleukodystrophy) or physical cause (e.g. adrenal haemorrhage) is found. Establishing the underlying basis of adrenal failure can have important implications for investigating associated features, the likely long-term approach to treatment, and for counselling families about the risk of other children being affected.

  3. Exposure to monocrotophos pesticide causes disruption of the hypothalamic-pituitary-thyroid axis in adult male goldfish (Carassius auratus).

    Science.gov (United States)

    Zhang, Xiaona; Tian, Hua; Wang, Wei; Ru, Shaoguo

    2013-11-01

    The thyroid hormones (THs) 3,3',5-triiodo-l-thyronine (T3) and l-thyroxine (T4) exert a wide range of biological effects on physiological processes of fish. To elucidate the thyroid disruption effects of monocrotophos (MCP), an organophosphate pesticide, on male goldfish (Carassius auratus), thyroid follicle histology, plasma total T3 (TT3), total T4 (TT4), free T3 (FT3) and free T4 levels, and the mRNA expression of indices involved in the hypothalamic-pituitary-thyroid axis (HPT axis) were examined following 21-day exposure to 0.01, 0.10 and 1.00mg/L of a 40% MCP-based pesticide. The results showed that MCP exposure induced the hyperplasia and hypertrophy of thyroid follicular epithelium and led to decreased plasma TT3 levels and TT3-to-TT4 ratios, without effect on plasma TT4 levels. Profiles of the changes in the relative abundance of deiodinase (D1, D2 and D3) transcripts were observed in the liver, brain and kidneys, during MCP exposure. An increase in the metabolism of T3, expressed as highly elevated hepatic d1 and d3 mRNA levels, might be associated with the reduction in plasma TT3 levels in both the 0.01 and 0.10mg/L groups, while in the 1.00mg/L MCP group, inhibited hepatic d2 transcripts might have also resulted in decreased TT3 levels by preventing the activation of T4 to T3. As a compensatory response to decreased T3 levels, pituitary thyroid-stimulating hormone β subunit mRNA transcription was up-regulated by the MCP pesticide. Decreases in plasma FT3 levels were also correlated with the modulation of hepatic transthyretin mRNA expression. Overall, the MCP pesticide exhibited thyroid-disrupting effects via interference with the HPT axis at multiple potential sites, resulting in disturbance of TH homeostasis. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Homeostatic Control of the Thyroid Pituitary Axis: Perspectives for Diagnosis and Treatment

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    Rudolf eHoermann

    2015-11-01

    Full Text Available The long-held concept of a proportional negative feedback control between the thyroid and pituitary gland requires reconsideration in the light of more recent studies. Homeostatic equilibria depend on dynamic interrelationships between thyroid hormones and pituitary thyrotropin (TSH. They display a high degree of individuality, thyroid-state-related hierarchy and adaptive conditionality. Molecular mechanisms involve multiple feedback loops on several levels of organization, different time scales and varying conditions of their optimum operation, including a proposed feedforward motif. This supports the concept of a dampened response and multistep regulation, making the interactions between TSH, FT4 and FT3 situational and mathematically more complex. As a homeostatically integrated parameter, TSH becomes neither normatively fixed nor a precise marker of euthyroidism. This is exemplified by the therapeutic situation with L-thyroxine (L-T4 where TSH levels defined for optimum health may not apply equivalently during treatment. In particular, an FT3-FT4 dissociation, discernible FT3-TSH disjoint and conversion inefficiency have been recognised in L-T4-treated athyreotic patients. In addition to regulating T4 production, TSH appears to play an essential role in maintaining T3 homeostasis by directly controlling deiodinase activity. While still allowing for tissue-specific variation this questions the currently assumed independence of the local T3 supply. Rather it integrates peripheral and central elements into an overarching control system. On L-T4 treatment, altered equilibria have been shown to give rise to lower circulating FT3 concentrations in the presence of normal serum TSH. While data on T3 in tissues are largely lacking in humans, rodent models suggest that the disequilibria may reflect widespread T3 deficiencies at the tissue level in various organs.As a consequence, the use of TSH, valuable though it is in many situations, should be

  5. The hypothalamic-pituitary-thyroid (HPT) axis in fish and its role in fish development and reproduction.

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    Blanton, Michael L; Specker, Jennifer L

    2007-01-01

    Bony fishes represent the largest vertebrate class and are a very diverse animal group. This chapter provides a thorough review of the available scientific literature on the thyroid system in these important vertebrate animals. The molecular components of the hypothalamic-pituitary-thyroid (HPT) axis in this group correspond closely to those of mammals. The thyroid tissue in the fishes is organized as diffuse follicles, with a few exceptions, rather than as an encapsulated gland as is found in most other vertebrate species. The features of this diffuse tissue in fishes are reviewed with an emphasis on feedback relationships within the HPT axis, the molecular biology of the thyroid system in fishes, and comparisons versus the thyroid systems of other vertebrate taxa. A review of the role of thyroid hormone in fish development and reproduction is included. Available information about the HPT axis in fishes is quite detailed for some species and rather limited or absent in others. This review focuses on species that have been intensively studied for their value as laboratory models in assays to investigate disruption in normal function of the thyroid system. In addition, in vitro and in vivo assay methods for screening chemicals for their potential to interfere with the thyroid system are reviewed. It is concluded that there are currently no in vitro or in vivo assays in fish species that are sufficiently developed to warrant recommendation for use to efficiently screen chemicals for thyroid disruption. Methods are available that can be used to measure thyroid hormones, although our ability to interpret the causes and implications of potential alterations in T4 or T3 levels in fishes is nonetheless limited without further research.

  6. Female nurses' burnout symptoms: No association with the Hypothalamic-pituitary-thyroid (HPT) axis.

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    Guo, Yufang; Lam, Louisa; Luo, Yuanhui; Plummer, Virginia; Cross, Wendy; Li, Hui; Yin, Yizhen; Zhang, Jingping

    2017-03-01

    Across the world, hospital nurses experience a high level of burnout. Exploring biochemical markers of burnout could help to understand physiological changes and may provide useful evidence for preventing burnout symptoms. The current study included 94 female nurses from one Chinese third-level hospital. The Maslach Burnout Inventory-General Survey (MBI-GS) was used to investigate burnout symptoms: emotional exhaustion, cynicism, reduced professional efficacy, as well as the burnout average. The HPT axis was tested by checking blood levels of thyroid-stimulating hormone (TSH), thyroxin (T4) and triiodothyronine (T3). Nonparametric tests showed that no significant difference in biochemical markers was found between the burnout and non-burnout groups. Spearman correlation analysis found that biochemical markers had no significant association with burnout symptoms, except weakly negative associations between reduced professional efficacy and blood pressure and heart rate. These findings show a rather poor correlation of the HPT axis on burnout symptoms. Expanding the biochemical index of the HPT axis, comparing well-defined samples and using longitudinal studies are recommended for further studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. The Petroselinum crispum L. hydroalcoholic extract effects on pituitary- gonad axis in adult Rats

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    F Bastampoor

    2014-07-01

    Full Text Available Background & aim: Infertility is one of the major issues in medical science which various chemical and herbal medicines have been used for its treatment from ancient times. Due to the side effects of chemical drugs and with regard to the cause of infertility in men is a hormonal disorder, thus, the study aimed to investigate the effect of ethanol extracts of parsley leaves performed on serum levels of pituitary - gonadal hormones. Methods: The present experimental study was conducted on fifty adult male rats. The animals were divided into 5 groups of 10 specimens, including controls, and three sets of empirical receiving doses 1000, 1500 and 2000 mg/kg ethanol extract of parsley leaves respectively. Prescriptions were done as gavage for 28 days. At the end of the test, the hearts of the animal and the serum hormones levels of testosterone, FSH and LH were measured. The Data were analyzed with t-test and Duncan and significant differences of data was considered at p = 0.05. Results: The findings revealed that the leaf extract of parsley caused a significant increase in FSH and LH and testosterone significantly increased at minimum and medium doses and decreased significantly in maximum dose. Conclusion: Parsley leaf , having antioxidant compounds, led to the increasing of FSH and LH hormones at three doses and increasing testosterone at minimum and medium doses and decreasing at maximum dose.

  8. Adrenal insufficiency and adrenal replacement therapy. Current status in Spain.

    Science.gov (United States)

    Aulinas, Anna; Casanueva, Felipe; Goñi, Fernando; Monereo, Susana; Moreno, Basilio; Picó, Antonio; Puig-Domingo, Manel; Salvador, Javier; Tinahones, Francisco J; Webb, Susan M

    2013-03-01

    Adrenal insufficiency (AI) is a rare endocrine disease, associated to increased mortality if left untreated. It can be due to a primary failure of the adrenal glands (primary AI) or malfunctioning of the hypothalamic-pituitary-adrenal axis (HPA) (secondary AI). The lack of data on incidence/prevalence of adrenal insufficiency in Spain complicates any evaluation of the magnitude of the problem in our country. Initial symptoms are non-specific, so often there is a delay in diagnosis. Current therapy with available glucocorticoids is associated with decreased quality of life in patients with treated AI, as well as with increased mortality and morbidity, probably related to both over-treatment and lack of hydrocortisone, associated with non-physiological peaks and troughs of the drug over the 24 hours. The availability of a new drug with a modified dual release (immediate and retarded), that requires one only daily dose, improves and simplifies the treatment, increases compliance as well as quality of life, morbidity and possibly mortality. This revision deals with the knowledge on the situation both globally and in Spain, prior to the availability of this new drug.

  9. [Hypogonadotropic hypogonadism: new aspects in the regulation of hypothalamic-pituitary-gonadal axis].

    Science.gov (United States)

    Brioude, F; Bouvattier, C-E; Lombès, M

    2010-09-01

    Hypogonadotropic hypogonadism (HH) is defined by the absence of sex steroid synthesis associated with the lack of appropriate gonadotrophin secretion. This leads to a variable degree of impuberism, often diagnosed during childhood or adolescence. Genetics of HH involve many genes. However, molecular defects have been identified in only 30 % of patients. Kallmann syndrome (KS) is defined by the association of HH and anosmia. Six genes are involved in KS (KAL1, FGFR1, FGF8, PROK2, PROKR2 and CHD7). However, genetics of KS is complex, because of the variability of the phenotype for a similar molecular defect. Otherwise, heterozygous anomalies are frequently described. Identification in the same patient of several mutations in some of these genes (digenism) could account for this variability. Autosomal recessive transmission is frequently observed in familial cases of HH without anosmia. Molecular alterations have been identified for several neuropeptides or their corresponding receptors, which are involved in the physiology of the gonadotropic axis : GNRHR, KISS1R/GPR54, neurokinin B (TAC3), TACR3 and GNRH1 (and PROK2, PROKR2 and CHD7). Anomalies of leptin or its receptor are also involved in HH cases. A new negative regulating element has been recently identified in humans : RFRP3, which is ortholog of the avian GnIH (gonadotrophin inhibitory hormone). Recent progress about these neuropeptides leads to a new model of comprehension of the gonadotropic axis physiology, from a linear model to a network model, which regulates the central element of regulation of the gonadotropic axis, represented by the GnRH neurons.

  10. New insights into the role of perinatal HPA-axis dysregulation in postpartum depression.

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    Glynn, Laura M; Davis, Elysia Poggi; Sandman, Curt A

    2013-12-01

    Postpartum depression affects 10-20% of women following birth and exerts persisting adverse consequences on both mother and child. An incomplete understanding of its etiology constitutes a barrier to early identification and treatment. It is likely that prenatal hormone trajectories represent both markers of risk and also causal factors in the development of postpartum depression. During pregnancy the maternal hypothalamic-pituitary-adrenal axis undergoes dramatic alterations, due in large part, to the introduction of the placenta, a transient endocrine organ of fetal origin. We suggest that prenatal placental and hypothalamic-pituitary-adrenal axis dysregulation is predictive of risk for postpartum depression. In this model the positive feedback loop involving the systems regulating the products of the HPA axis results in higher prenatal levels of cortisol and placental corticotropin-releasing hormone. Greater elevations in placental corticotropin-releasing hormone are related to a disturbance in the sensitivity of the anterior pituitary to cortisol and also perhaps to decreased central corticotropin-releasing hormone secretion. Secondary or tertiary adrenal insufficiencies of a more extreme nature, which emerge during the prenatal period, may be predictive of an extended or more pronounced postpartum hypothalamic-pituitary-adrenal refractory period, which in turn represents a risk factor for development of postpartum depression. In addition to reviewing the relevant existing literature, new data are presented in support of this model which link elevated placental corticotropin-releasing hormone with low levels of ACTH at 3-months postpartum. Future research will further elucidate the role of hypothalamic-pituitary-adrenal axis dysregulation in postpartum depression and also whether prenatal placental and hypothalamic-pituitary-adrenal profiles might prove useful in the early identification of mothers at risk for postpartum mood dysregulation. Copyright © 2013

  11. 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.

  12. Using bedtime (PM) and early morning (AM) urine cortisol/creatinine ratios to evaluate pituitary-adrenal function in an office practice.

    Science.gov (United States)

    Burch, Warner

    2011-01-01

    To evaluate the use of cortisol/creatinine ratios in urine specimens collected at bedtime (PM) and the following morning (AM) in a general endocrine practice as a means of assessing pituitary-adrenal function in normal volunteers, outpatients with symptoms but no clinical endocrine dysfunction, patients with Cushing syndrome, and patients with known hypopituitarism. Double-voided PM and AM urine samples were collected from 26 healthy control subjects and 131 outpatients who had complaints of fatigue and malaise, inability to lose weight, or nonspecific concerns about potential underlying problems with their metabolism. The findings on physical examination and laboratory studies were normal in each of these outpatients. Urine was assayed for free cortisol and creatinine and expressed as ng of cortisol/mg of creatinine. Eleven patients with documented Cushing syndrome also collected urine specimens, and data for 11 patients with known hypopituitarism were also studied. A clear diurnal pattern of low cortisol excretion at night that increased some 7-fold in the morning (PAM cortisol/creatinine was 91.5 (95% CI, 65.0 to 118.0). The mean AM/PM ratio was 6.9, and the mean difference in AM-PM was 75.7. In the outpatients, there was no significant difference in PM, AM, AM/PM, and AM-PM values in comparison with those in healthy control subjects, and no significant difference was noted in these variables among the 3 groups of outpatients (those with fatigue, weight gain, and metabolism concerns). In 11 patients with Cushing syndrome, the mean PM urine cortisol/creatinine ratio was 127.0 (95% CI, 87.0 to 166.0), and there was loss of diurnal variation with the AM/PM ratio of 1.16 (95% CI, 0.98 to 1.35). Patients with hypopituitarism had little to no increase in AM urine cortisol/creatinine in comparison with PM urine cortisol/creatinine. Determination of PM and AM urine cortisol/creatinine ratios offers a convenient method for assessing pituitary-adrenal function.

  13. Activation in the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system in women with carpal tunnel syndrome.

    Science.gov (United States)

    Fernández-de-Las-Peñas, César; Díaz-Rodríguez, Lourdes; Salom-Moreno, Jaime; Galiano-Castillo, Noelia; Valverde-Herreros, Lis; Martínez-Martín, Javier; Pareja, Juan A

    2014-08-01

    The aim of this study is to investigate the differences in salivary cortisol (hypothalamic-pituitary-adrenocortical [HPA] axis), α-amylase activity (sympathetic nervous system [SNS]), and immunoglobulin A (IgA; immune system) concentrations between women with carpal tunnel syndrome (CTS) and healthy women. A cross-sectional study. Activation of HPA, SNS, and immune system in CTS has not been clearly determined. One hundred two women (age: 45 ± 7 years) with electrodiagnostic and clinical diagnosis of CTS and 102 matched healthy women. The intensity of the pain was assessed with a Numerical Pain Rating Scale (0-10), and disability was determined with Boston Carpal Tunnel Questionnaire. Salivary cortisol concentration, α-amylase activity, salivary flow rate, and IgA concentration were collected from nonstimulated saliva. Women with CTS exhibited lower salivary flow rate (P  0.2) were found between groups as a total. Women with severe CTS exhibited lower salivary flow rate (P < 0.001), higher α-amylase activity (P = 0.002), and higher cortisol concentration (P = 0.03) than healthy women and than those with minimal/moderate CTS (P < 0.05). Within women with CTS, significant positive associations between α-amylase activity and the intensity of pain were found: the highest the level of pain, the higher the α-amylase activity, i.e., higher SNS activation. These results suggest that women with severe CTS exhibit changes in activation in the HPA axis and SNS but not in the humoral immune system. Activation of the SNS was associated with the intensity of pain. Future studies are needed to elucidate the direction of this relationship. Wiley Periodicals, Inc.

  14. The Effects of Disturbance on Hypothalamus-Pituitary-Thyroid (HPT Axis in Zebrafish Larvae after Exposure to DEHP.

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    Pan-Pan Jia

    Full Text Available Di-(2-ethylhexyl phthalate (DEHP has the potential to disrupt the thyroid endocrine system, but the underlying mechanism is unknown. In this study, zebrafish (Danio rerio embryos were exposed to different concentrations of DEHP (0, 40, 100, 200, 400 μg/L from 2 to 168 hours post fertilization (hpf. Thyroid hormones (THs levels and transcriptional profiling of key genes related to hypothalamus-pituitary-thyroid (HPT axis were examined. The result of whole-body thyroxine (T4 and triiodothyronine (T3 indicated that the thyroid hormone homeostasis was disrupted by DEHP in the zebrafish larvae. After exposure to DEHP, the mRNA expressions of thyroid stimulating hormone (tshβ and corticotrophin releasing hormone (crh genes were increased in a concentration dependent manner, respectively. The expression level of genes involved in thyroid development (nkx2.1 and pax8 and thyroid synthesis (sodium/iodide symporter, nis, thyroglobulin, tg were also measured. The transcripts of nkx2.1 and tg were significantly increased after DEHP exposure, while those of nis and pax8 had no significant change. Down-regulation of uridinediphosphate-glucuronosyl-transferase (ugt1ab and up-regulation of thyronine deiodinase (dio2 might change the THs levels. In addition, the transcript of transthyretin (ttr was up-regulated, while the mRNA levels of thyroid hormone receptors (trα and trβ remained unchanged. All the results demonstrated that exposure to DEHP altered the whole-body thyroid hormones in the zebrafish larvae and changed the expression profiling of key genes related to HPT axis, proving that DEHP induced the thyroid endocrine toxicity and potentially affected the synthesis, regulation and action of thyroid hormones.

  15. Interaction involving the thymus and the hypothalamus-pituitary axis, immunomodulation by hormones

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    Marković Ljiljana 2

    2004-01-01

    Full Text Available Perfectly projected and impeccably created, the endocrine system precisely regulates the most delicate immune processes. The immune and neuroendocrine systems are two essential physiological components of mammalian organisms important for protection from the infection and disease on one hand, and on the other, for regulation of metabolism and other physiological activities; namely, the evidence has been found indicating that there is active and dynamic collaboration of these systems in the execution of their designated functions [1, 2,4]. These interactions occur at many stages of embryonic and neonatal development, and they are a continual part of normal homeostatic balance necessary to preserve health. There is communication between neuroendocrine and immune system via cytokines, neurotransmitters and peptide hormones which act, in both systems, through the same receptor molecules (Scheme 1. Many investigators have reported the increased thymic weight in experimental animals due to both castration and adrenalectomy [4]. The discovery from 1898 revealing that thymus was enlarged in castrated rabbits has been considered the embryo of hybrid medical discipline, i.e. the immunoendocrinology [1]. In the actual literature, at least in that available to us, it has not been noted that the appearance of the eunuchs, i.e. the castrates, stimulated the analytical approach to this phenomenon. Endocrine influences appear to be a part of bidirectional circuitry, namely, thymic hormones also regulate the release of hormones from the pituitary gland. Physiologically, thymus is under neuroendocrine control. It is apparent that the circulating levels of distinct peptide hormones are necessary to maintain a series of biological functions related both to micro environmental and lymphoid cells of the organ. The neuroendocrine control of the thymus appears to be extremely complex, with apparent presence of complete intrathymic biological circuitry involving the

  16. The Effect of Chelidonium majus Extract on the Lipid Profile and Activity of Pituitary-Gonadal Axis in Hypercholesterolemic Rats

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    Saeed Changizi-Ashtiyani

    2014-10-01

    Full Text Available Background: Over the past centuries, global population has increased at different rates and so has been the case with cardiovascular diseases. Therefore, given the importance of population and cholesterol control, the purpose of this study is to investigate the effect of Chelidonium majus (C. majus aerial parts extract on the lipid profile and prolactin levels and the activity of pituitary-gonadal axis in hypercholesterolemic rats. Materials and Methods: In this experimental study, 35 Wistar rats were selected and categorized into 5 groups. The control group had ordinary diet, the model group had high-fat diet, and experimental groups consisted of hypercholesterolemic rats that respectively received minimal dosages of 100, 200 and 300 mg/kg of C. majus extract. After 21 days, blood samples were taken and the factors of interest were measured. Then, the gathered data were analyzed using SPSS-11.5. Results: The amount of triglyceride and cholesterol were increased in the model group compared to the control group whereas the same items were decreased in the experimental group. C. majus extract also decreased testosterone and increased prolactin and gonadotropins. Conclusion: In this study, C. majus extract resulted in decreased fat and testosterone levels as well as increased prolactin level; however, since many sources have informed of the toxicity of this plant, cautious use of the plant is advised.

  17. Chronic Administration of High Doses of Nandrolone Decanoate on the Pituitary-Gonadal Axis in Male Rats

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    Shahraki

    2015-09-01

    Full Text Available Background Anabolic-androgenic steroids (AAS are abused by athletes. Objectives The present study was designed to evaluate chronic administration of high doses of nandrolone decanoate (ND on the pituitary-gonadal axis and hematological parameters in normal male rats. Materials and Methods Thirty Wistar-Albino male rats were divided assigned to control (C, placebo (P and test (T groups (n = 10. Group T received 15 mg/kg intramuscular (IM ND for eight weeks. Group P received the same volume of peanut oil, but group C did not receive any agent during the trial period. At the end, animals were anesthetized, killed and blood samples collected from cervical vessels. Serum follicle stimulating hormone (FSH and luteinizing hormone (LH levels were determined by sensitive rat gonadotropins kit, using ELISA methods. Serum testosterone and hematological parameters were measured by ordinary laboratory methods. Obtained data was analyzed using SPSS 17 by ANOVA and Tukey statistical tests. Results were expressed as Mean ± SD. Statistical difference considered significantly by P < 0.05. Results Serum testosterone, LH, FSH, weight gain, food and water intake in group T were significantly decreased compared to other groups (P < 0.05. In addition erythrocyte, leucocytes, hemoglobin and hematocrit in group T were significantly increased compared to those of other groups (P < 0.05. Conclusions Chronic administration of high doses of ND can alter serum FSH, LH and testosterone and hematological parameters in male rats.

  18. The Effect of an Angiotensin II Antagonist on Hormones of Pituitary-Gonad Axis in Adult Male Rats

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    S. Ebrahim Hosseini

    2014-02-01

    Full Text Available Background: The aim of this study was to investigate the effect of valsartan, an angiotensin II antagonist, on the function of the pituitary- gonad axis. Materials and Methods: Adult male Wistar rats (200 to 220 g were used as experimental and control groups. The 3 experimental groups received either 100, 200, or 400 mg/kg/day valsartan in 1 ml water orally for 28 days, while a set of control group received 1 ml distilled water for the same period of time and another set received no treatment. At the end of the experimental period, blood was collected and serum was analyzed for FSH, LH, testosterone and dihydrotestosterone levels by RIA methods. Results: There were no significant differences among FSH levels at all doses of valsartan used, while the serum LH level was decreased significantly at the maximum dose of the drug used. Serum testosterone level decreased at both the 200 and 400 mg/kg dose compared to the control, while the dihydrotestosterone level was reduced significantly at all the three dosages used. Conclusion: According to our founding, suggested that the effects of valsartan on serum LH, testosterone and dihydrotestosterone may be mediated through angiotensin II receptor.

  19. The hypothalamus-pituitary-thyroid axis in teleosts and amphibians: Endocrine disruption and its consequences to natural populations

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    Carr, J.A.; Patino, R.

    2011-01-01

    Teleosts and pond-breeding amphibians may be exposed to a wide variety of anthropogenic, waterborne contaminants that affect the hypothalamus-pituitary-thyroid (HPT) axis. Because thyroid hormone is required for their normal development and reproduction, the potential impact of HPT-disrupting contaminants on natural teleost and amphibian populations raises special concern. There is laboratory evidence indicating that persistent organic pollutants, heavy metals, pharmaceutical and personal care products, agricultural chemicals, and aerospace products may alter HPT activity, development, and reproduction in teleosts and amphibians. However, at present there is no evidence to clearly link contaminant-induced HPT alterations to impairments in teleost or amphibian population health in the field. Also, with the exception of perchlorate for which laboratory studies have shown a direct link between HPT disruption and adverse impacts on development and reproductive physiology, little is known about if or how other HPT-disrupting contaminants affect organismal performance. Future field studies should focus on establishing temporal associations between the presence of HPT-disrupting chemicals, the occurrence of HPT alterations, and adverse effects on development and reproduction in natural populations; as well as determining how complex mixtures of HPT contaminants affect organismal and population health. ?? 2010 Elsevier Inc.

  20. Sex-dependent effects of microcystin-LR on hypothalamic-pituitary-gonad axis and gametogenesis of adult zebrafish

    Science.gov (United States)

    Liu, Wanjing; Chen, Chuanyue; Chen, Liang; Wang, Li; Li, Jian; Chen, Yuanyuan; Jin, Jienan; Kawan, Atufa; Zhang, Xuezhen

    2016-03-01

    While microcystins (MCs) have been reported to exert reproductive toxicity on fish with a sex-dependent effect, the underlying mechanism has been rarely investigated. In the present study, zebrafish were exposed to 1, 5 and 20 μg/L MC-LR for 30 d. The gonad-somatic index declined in all treated males. 17β-estradiol (E2), testosterone (T), 11-keto testosterone (11-KT) and follicle-stimulating hormone (FSH) levels increased in serum from all treated females, while T, FSH and luteinizing hormone (LH) levels changed in all treated males. Histomorphological observation showed that MC-LR exposure evidently retarded oogenesis and spermatogenesis. Transcriptional changes of 22 genes of the hypothalamic-pituitary-gonad (HPG) axis exhibited sex-specific responses, and the relationship between gene transcriptions and gametogenesis was evaluated by principle component analysis (PCA). Major contributors to PC1 (gnrh2, gnrhr3, ar, lhr, hmgra, hmgrb and cyp19a) were positively correlated with the number of post-vitellogenic oocytes, while PC1 (gnrh2, lhβ, erβ, fshr, cyp11a and 17βhsd) were positively correlated with the number of spermatozoa. The protein levels of 17βHSD and CYP19a were affected in both females and males. In conclusion, this study first investigated the sex-dependent effects of microcystins on fish reproduction and revealed some important molecular biomarkers related to gametogenesis in zebrafish suffered from MC-LR.

  1. Higher levels of physical activity are associated with lower hypothalamic-pituitary-adrenocortical axis reactivity to psychosocial stress in children.

    Science.gov (United States)

    Martikainen, Silja; Pesonen, Anu-Katriina; Lahti, Jari; Heinonen, Kati; Feldt, Kimmo; Pyhälä, Riikka; Tammelin, Tuija; Kajantie, Eero; Eriksson, Johan G; Strandberg, Timo E; Räikkönen, Katri

    2013-04-01

    Children who undertake more physical activity (PA) not only have more optimal physical health but also enjoy better mental health. However, the pathways by which PA affects well-being remain unclear. To address this question, we examined whether objectively measured daytime PA was associated with diurnal hypothalamic-pituitary-adrenocortical axis (HPAA) activity and HPAA responses to psychosocial stress. We conducted a cross-sectional study in a birth cohort in Helsinki, Finland. We studied 258 8-year-old children. PA was assessed with wrist-worn accelerometers. Overall PA and percentage of time spent in vigorous PA (VPA) were categorized by sex into thirds. Salivary cortisol was measured diurnally and in response to the Trier Social Stress Test for Children. The children in different PA groups did not show differences in diurnal salivary cortisol (P > .10 for overall PA and VPA). Children with the highest levels of overall PA or VPA showed no, or only small, increases over time in salivary cortisol after stress (P = .10 and P =.03 for time in analyses of PA and VPA, respectively), whereas children belonging to the lowest and intermediate thirds showed significant increases over time in salivary cortisol after stress (P ≤ .002 for time in the analyses of overall PA and VPA). These results suggest that children with lower levels of daytime PA have higher HPAA activity in response to stress. These findings may offer insight into the pathways of PA on physical and mental well-being.

  2. PCB disruption of the hypothalamus-pituitary-interrenal axis involves brain glucocorticoid receptor downregulation in anadromous Arctic charr

    Science.gov (United States)

    Aluru, N.; Jorgensen, E.H.; Maule, A.G.; Vijayan, M.M.

    2004-01-01

    We examined whether brain glucocorticoid receptor (GR) modulation by polychlorinated biphenyls (PCBs) was involved in the abnormal cortisol response to stress seen in anadromous Arctic charr (Salvelinus alpinus). Fish treated with Aroclor 1254 (0, 1, 10, and 100 mg/kg body mass) were maintained for 5 mo without feeding in the winter to mimic their seasonal fasting cycle, whereas a fed group with 0 and 100 mg/kg Aroclor was maintained for comparison. Fasting elevated plasma cortisol levels and brain GR content but depressed heat shock protein 90 (hsp90) and interrenal cortisol production capacity. Exposure of fasted fish to Aroclor 1254 resulted in a dose-dependent increase in brain total PCB content. This accumulation in fish with high PCB dose was threefold higher in fasted fish compared with fed fish. PCBs depressed plasma cortisol levels but did not affect in vitro interrenal cortisol production capacity in fasted charr. At high PCB dose, the brain GR content was significantly lower in the fasted fish and this corresponded with a lower brain hsp70 and hsp90 content. The elevation of plasma cortisol levels and upregulation of brain GR content may be an important adaptation to extended fasting in anadromous Arctic charr, and this response was disrupted by PCBs. Taken together, the hypothalamus-pituitary- interrenal axis is a target for PCB impact during winter emaciation in anadromous Arctic charr.

  3. The changes in the hypothalamo-pituitary-gonadal axis of streptozotocin-treated male rats depend from age at diabetes onset.

    Science.gov (United States)

    Pitton, I; Bestetti, G E; Rossi, G L

    1987-01-01

    The influence of age at diabetes onset and of capillary microangiopathy on the severity and evolution of hypothalamo-pituitary-gonadal changes was studied morphologically and morphometrically in male rats 4 and 8 months after streptozotocin injection. At each time period we studied 2 groups of rats, one made diabetic before (age 1 month), the other after puberty (age 3 months), and compared them with corresponding controls. The size of hypothalamic axons, numerical density and size of pituitary gonadotrophs, size of testicular tubules, and basement membrane thickness of retinal capillaries were measured. Major differences were found at 8 months. Changes of pituitary glands (i.e. small and numerous gonadotrophs) and testes (i.e. small tubular size) were more important in pre- than in postpubertal diabetic rats. This was a consequence of the aggravating prepubertal diabetes between 4 and 8 months. On the contrary, these changes partially regressed in postpubertal diabetic animals. Pituitary and testicular changes were correlated. Other lesions, such as swollen axonal processes in the hypothalamus, increased thickness of seminiferous epithelium and of capillary basement membranes, though very evident in diabetics, were independent from age at induction. Neither microangiopathy nor glycemia were correlated with any other change which confirmed their secondary role in diabetic neuroendocrine disorders. Thus, two types of diabetic disorders of the hypothalamo-pituitary-gonadal axis could be distinguished: 1) those with irreversible effects on immature yet partially reversible effects on mature structures; and 2) those independent from age at induction.

  4. Receptors of Hypothalamic-Pituitary-Ovarian-Axis Hormone in Uterine Myomas

    Directory of Open Access Journals (Sweden)

    Danuta Plewka

    2014-01-01

    Full Text Available In this study the expression of GnRH, FSH, LH, ER-α, ER-β, and PR receptors was examined in uterine myomas of women in reproductive and perimenopausal age. In cases of GnRH and tropic hormones a membranous and cytoplasmic immunohistochemical reaction was detected, in cases of ER-α and PR the reaction was located in cell nucleus, and in the case of ER-β it manifested also a cytoplasmic location. In some of the examined cases the expression was detected in endometrium, myocytes, and endothelium of blood vessels, in uterine glands and myoma cells. In myometrium the level of GnRH and LH receptors increases with age, whereas the level of progesterone and both estrogen receptors decreases. In myomas of women in reproductive age, independently of their size, expression of GnRH, FSH, and LH receptors was more pronounced than in myometrium. In women of perimenopausal age, independently of myoma size, expression of LH and estrogen α receptors was higher while expression of GnRH receptors was lower than in myometrium. FSH receptor expression was not observed. Expression of estrogen receptor β was not affected by age of the woman or size of myoma. Analysis of obtained results indicates on existing in small myomas local feedback axis between GnRH-LH-progesterone.

  5. Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

    OpenAIRE

    Hojatollah Karimi Jashni; Hossein Kargar Jahromi; Ali Ghorbani Ranjbary

    2016-01-01

    Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses ...

  6. Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

    OpenAIRE

    Karimi Jashni, Hojatollah; Kargar Jahromi, Hossein; Ghorbani Ranjbary, Ali; Kargar Jahromi, Zahra; Khabbaz Kherameh, Zahra

    2016-01-01

    Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses (100, ...

  7. 甲状腺激素与下丘脑-垂体-性腺轴%Thyroid Hormone and Hypothalamic-Pituitary-Gonadal Axis

    Institute of Scientific and Technical Information of China (English)

    罗兰; 牛敏; 高政南

    2016-01-01

    生殖功能的调节主要是由下丘脑-垂体-性腺轴各环节共同完成,适量的甲状腺激素有助于维持垂体-性腺轴的稳定。一旦甲状腺功能发生紊乱,将会影响性激素分泌水平及性腺功能,造成不孕不育等,给人们的生活带来了极大的不便。同时甲状腺功能异常引起的代谢紊乱也会进一步增加不孕不育的风险。本文将对TH与下丘脑-垂体-性腺轴的关系进行简单阐述。%The regulation of reproductive function is mainly completed by the hypothalamic pituitary gonadal axis of each link together, the amount of thyroid hormone helps to maintain the stability of the pituitary gonadal axis. Once the thyroid function is disorder, it will affect the level of sex hormone secretion and gonadal function, causing infertility, bringing great inconvenience to people's life. At the same time, metabolic disorder caused by abnormal thyroid function will further increase the risk of infertility. This article briefly elaborates on the relationship between TH and the hypothalamic pituitary gonadal axis.

  8. Disturbances in Hypothalamic-Pituitary-Adrenal Axis and Immunological Activity Differentiating between Unipolar and Bipolar Depressive Episodes

    NARCIS (Netherlands)

    Becking, Karlijn; Spijker, Annet T.; Hoencamp, Erik; Penninx, Brenda W. J. H.; Schoevers, Robert A.; Boschloo, Lynn

    2015-01-01

    Introduction Differentiating bipolar depression (BD) from unipolar depression (UD) is difficult in clinical practice and, consequently, accurate recognition of BD can take as long as nine years. Research has therefore focused on the discriminatory capacities of biomarkers, such as markers of the

  9. Dysfunction of the hypothalamic-pituitary-adrenal axis and functional somatic symptoms : A longitudinal cohort study in the general population

    NARCIS (Netherlands)

    Tak, Lineke M.; Bakker, Stephan J. L.; Rosmalen, Judith G. M.

    In persons with functional somatic symptoms (FSS), no conventionally defined organic pathology is apparent. It has been suggested that complex interactions of psychological, physiological, and social factors are involved in the etiology of FSS. One of the physiological mechanisms that may contribute

  10. Antiglucocorticoid RU 38486 attenuates retention of a behaviour and disinhibits the hypothalamic-pituitary adrenal axis at different brain sites

    NARCIS (Netherlands)

    De Kloet, E R; De Kock, Susanne E.; Schild, V; Veldhuis, H D

    1988-01-01

    Adrenalectomized rats displayed a deficiency in retention of an immobility response acquired during an initial 15-min forced swimming procedure (Porsolt swimming test) and measured 24 h later in a 5-min retest session. The deficit could be restored dose dependently with the glucocorticoid dexamethas

  11. Metabolic changes, hypothalamo-pituitary-adrenal axis and oxidative stress after short-term starvation in healthy pregnant women

    OpenAIRE

    Schraag, Sabrina; Mandach, Ursula von; Schweer, Horst; Beinder, Ernst

    2017-01-01

    Aim: To compare metabolic effects and oxidative stress in pregnant and non-pregnant women after 12h of fasting. Methods: Twenty-six healthy women with uncomplicated singleton pregnancies between the 24th and 28th gestational week were recruited. After an overnight fast, venous blood samples and urine samples were tested for metabolic parameters characteristic for starvation, cortisol and oxidative stress products. Healthy non-pregnant women matched by age, body mass index and length of fastin...

  12. Anticipation of public speaking and sleep and the hypothalamic-pituitary-adrenal axis in women with irritable bowel syndrome.

    Science.gov (United States)

    Heitkemper, M M; Cain, K C; Deechakawan, W; Poppe, A; Jun, S-E; Burr, R L; Jarrett, M E

    2012-07-01

    Evidence suggests that subgroups of patients with irritable bowel syndrome (IBS) are hyper-responsive to a variety of laboratory stress conditions. This study compared sleep quality and night time plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels in response to anticipation of public speaking between 43 women with IBS and 24 healthy control women. In addition, comparisons were made between subgroups within the IBS sample based on predominant stool patterns, 22 IBS-constipation and 21 IBS-diarrhea. Subjects slept three nights in a sleep laboratory, and on the third night serial blood samples were drawn every 20 min from 08:00 PM until awakening. As the subjects had different sleep onsets, each subject's results were synchronized to the first onset of stage 2 sleep. Compared the healthy control group, women with IBS had significantly worse sleep efficiency, and higher cortisol but not ACTH levels over the night. However, there were no IBS bowel pattern subgroup differences. Among IBS subjects, cortisol levels early in the night were higher than found in our previous study with a similar protocol but without the threat of public speaking. These results suggest that a social stressor, such as public speaking prior to bedtime, increases cortisol but not ACTH levels suggesting HPA dysregulation in women with IBS. This response to a social stressor contributes to our understanding of the relationship of stress to symptom expression in IBS. © 2012 Blackwell Publishing Ltd.

  13. The role of estrogen in hypothalamic regulation of hypothalamus-pituitary-adrenal axis activity, energy homeostasis and bone metabolism

    NARCIS (Netherlands)

    Liu, J.

    2013-01-01

    Sex differences have been found in many homeostatic domains, including the stress response, energy metabolism and fat distribution. In the present thesis, I study the involvement of the female hormone estrogen in the occurrence of these sex-differences, more specifically I focused on the brain-media

  14. Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null mice reveals hypergonadism and endocrine sex reversal in females lacking ERalpha but not ERbeta.

    Science.gov (United States)

    Couse, John F; Yates, Mariana M; Walker, Vickie R; Korach, Kenneth S

    2003-06-01

    To determine the role of each estrogen receptor (ER) form (ERalpha, ERbeta) in mediating the estrogen actions necessary to maintain proper function of the hypothalamic-pituitary-gonadal axis, we have characterized the hypothalamic-pituitary-gonadal axis in female ER knockout (ERKO) mice. Evaluation of pituitary function included gene expression assays for Gnrhr, Cga, Lhb, Fshb, and Prl. Evaluation of ovarian steroidogenic capacity included gene expression assays for the components necessary for estradiol synthesis: i.e. Star, Cyp11a, Cyp17, Cyp19, Hsd3b1, and Hsd17b1. These data were corroborated by assessing plasma levels of the respective peptide and steroid hormones. alphaERKO and alphabetaERKO females exhibited increased pituitary Cga and Lhb expression and increased plasma LH levels, whereas both were normal in betaERKO. Pituitary Fshb expression and plasma FSH were normal in all three ERKOs. In the ovary, all three ERKOs exhibited normal expression of Star, Cyp11a, and Hsd3b1. In contrast, Cyp17 and Cyp19 expression were elevated in alphaERKO but normal in betaERKO and alphabetaERKO. Plasma steroid levels in each ERKO mirrored the steroidogenic enzyme expression, with only the alphaERKO exhibiting elevated androstenedione and estradiol. Elevated plasma testosterone in alphaERKO and alphabetaERKO females was attributable to aberrant expression of Hsd17b3 in the ovary, representing a form of endocrine sex reversal, as this enzyme is unique to the testes. Enhanced steroidogenic capacity in alphaERKO ovaries was erased by treatment with a GnRH antagonist, indicating these phenotypes to be the indirect result of excess LH stimulation that follows the loss of ERalpha in the hypothalamic-pituitary axis. Overall, these findings indicate that ERalpha, but not ERbeta, is indispensable to the negative-feedback effects of estradiol that maintain proper LH secretion from the pituitary. The subsequent hypergonadism is illustrated as increased Cyp17, Cyp19, Hsd17b1, and

  15. In Search of HPA Axis Dysregulation in Child and Adolescent Depression

    Science.gov (United States)

    Guerry, John D.; Hastings, Paul D.

    2011-01-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in adults with major depressive disorder is among the most consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development and recurrence of depressive phenomena over the lifespan, it is important to have an integrative…

  16. Role of estrogen receptors (ERs and G protein-coupled estrogen receptor (GPER in regulation of hypothalamic-pituitary-testis axis and spermatogenesis

    Directory of Open Access Journals (Sweden)

    Adele eChimento

    2014-01-01

    Full Text Available Male reproductive function is under the control of both gonadotropins and androgens through a negative feedback loop that involves the hypothalamus, pituitary and testis known as hypothalamus-pituitary-gonadal axis (HPG. Indeed, also estrogens play an important role in regulating HPG axis but the relative contribution to the inhibition of gonadotropins secretion exerted by the amount of estrogens produced within the hypothalamus and/or the pituitary or by the amount of circulating estrogens are still ongoing. Moreover, it is known that maintenance of spermatogenesis is controlled by gonadotrophins and testosterone, the effects of which are modulated by a complex network of locally produced factors, including estrogens. Physiological effects of estrogens are mediated by the classical nuclear estrogen receptor alpha (ESR1 and estrogen receptor beta (ESR2, which mediate both genomic and rapid signaling events. In addition, estrogens induce rapid non-genomic responses through a membrane-associated G protein-coupled receptor (GPER. Ours and other studies reported that, in the testis, GPER is expressed in both normal germ cells and somatic cells and it is involved in mediating the estrogen action in spermatogenesis controlling proliferative and/or apoptotic events. Interestingly, GPER expression has been revealed also in hypothalamus and in pituitary. However, its role in mediating estrogen rapid actions in this context is under investigation. Recent studies indicate that GPER is involved in modulating GnRH release as well as gonadotropins secretion. In this review, we will summarize the current knowledge concerning the role of estrogen/estrogen receptors (ERs molecular pathways in regulating GnRH, FSH and LH release at hypothalamic and pituitary level in male as well as in controlling specific testicular functions such as spermatogenesis, focusing our attention mainly on estrogen signaling mediated by GPER.

  17. Studies on the functional relationship between thyroid, adrenal and gonadal hormones.

    Science.gov (United States)

    Tohei, Atsushi

    2004-02-01

    In order to clarify the functional relationship between thyroid, adrenal and gonadal hormones, hypothyroidism was induced by administration of thiuoracil in adult male and female rats, and the effects of hypothyroidism on the adrenal and the gonadal axes were investigated in the present study. 1. The functional relationship between thyroid and adrenal hormones: Adrenal weights and corticosterone were lowered, whereas the secretion of ACTH, corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) increased in hypothyroid rats compared to euthyroid rats. These results indicate that hypothyroidism causes adrenal dysfunction directly and results in hypersecretion of CRH and AVP from the hypothalamus. 2. The functional relationship between thyroid and gonadal hormones: The pituitary response to LHRH was lowered, whereas the testicular response to hCG was not changed in hypothyroid rats. Hypothyroidism suppressed copulatory behavior in male rats. These results suggest that hypothyroidism probably causes dysfunction in gonadal axis at the hypothalamic-pituitary level in male rats. In adult female rats, hypothyroidism inhibited the follicular development accompanied estradiol secretion, whereas plasma concentrations of progesterone and prolactin (PRL) increased in hypothyroid female rats. Hypothyroidism significantly increased the pituitary content of vasoactive intestinal peptide (VIP) though it did not affect dopamine synthesis. These results suggest that hypothyroidism increases pituitary content of VIP and this increased level of VIP likely affects PRL secretion in a paracrine or autocrine manner. In female rats, inhibition of gonadal function in hypothyroid rats mediated by hyperprolactinemia in addition to hypersecretion of endogenous CRH.

  18. Defining global gene expression changes of the hypothalamic-pituitary-gonadal axis in female sGnRH-antisense transgenic common carp (Cyprinus carpio.

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    Jing Xu

    Full Text Available BACKGROUND: The hypothalamic-pituitary-gonadal (HPG axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus, 16 and 12 (pituitary, 119 and 93 (ovary, respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. CONCLUSIONS/SIGNIFICANCE: This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the

  19. Regulation of hypothalamic-pituitary-interrenal axis function in male smallmouth bass (Micropterus dolomieu) during parental care.

    Science.gov (United States)

    Jeffrey, J D; Cooke, S J; Gilmour, K M

    2014-08-01

    Male smallmouth bass (Micropterus dolomieu) provide sole parental care until offspring reach independence, a period of several weeks. During the early parental care period when males are guarding fresh eggs (MG-FE), cortisol responsiveness is attenuated; the response is re-established when males reach the end of the parental care period and are guarding free-swimming fry (MG-FSF). It was hypothesized that attenuation of the cortisol response in male smallmouth bass during early parental care reflected modulation of hypothalamic-pituitary-interrenal (HPI) axis function. Male smallmouth bass were sampled at the beginning (MG-FE) and end of the parental care period (MG-FSF), before and/or 25 min after exposure to a standardized stressor consisting of 3 min of air exposure. Repeated sampling of stressed fish for analysis of plasma cortisol and adrenocorticotropic hormone (ACTH) levels was carried out. Males significantly elevated both plasma cortisol and ACTH levels when guarding free-swimming fry but not during early parental care. Control and stressed fish were terminally sampled for tissue mRNA abundance of preoptic area (POA) and hypothalamic corticotropin-releasing factor (CRF) as well as head kidney melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc). No significant differences in either hypothalamus CRF or head kidney P450scc mRNA abundance were found across parental care stages or in response to stress. However, POA CRF mRNA abundance and interrenal cell MC2R and StAR mRNA abundances failed to increase in response to stress in MG-FE. Thus, the attenuated cortisol response in males guarding fresh eggs may be explained by hypoactive HPI axis function in response to stress. The present is one of few studies, and the first teleost study, to address the mechanisms underlying resistance to stress during the reproductive/parental care period. Copyright © 2014 Elsevier Inc. All rights

  20. Pituitary-gonadal hormones and adrenal androgens in non-cirrhotic female alcoholics after cessation of alcohol intake.

    Science.gov (United States)

    Välimäki, M; Pelkonen, R; Härkönen, M; Tuomala, P; Koistinen, P; Roine, R; Ylikahri, R

    1990-04-01

    To investigate the sex-hormone profiles associated with chronic alcoholism in women we examined 16 non-cirrhotic alcohol abusers (aged 18-46 years). They were admitted for the treatment of alcoholism (duration of 2-16 yrs) to a social hospital for 6 weeks. Their mean daily alcohol consumption was 170 g. Blood samples for serum LH, FSH, prolactin (PRL), oestrone (E1), oestradiol (E2), progesterone (P), 17-alpha-hydroxyprogesterone (17-OHP), androstenedione (A) and dehydroepiandrosterone (DHEA) were drawn three times a week during the hospital stay. Similar blood samples were taken from 10 control women during one menstrual cycle. The cycles were anovulatory in two patients and in none of controls. Serum LH and FSH levels were similar in alcoholic and control women but serum concentrations of PRL were increased 2-4-fold in alcoholic women. In the patients serum, concentrations of E1 and E2 tended to be lower during the follicular and midcycle phases, as did those of P and 17-OHP during the luteal phase. Compared with the controls, serum levels of A were increased 2-3-fold in the patients. A parallel difference between the two groups was seen in serum DHEA concentrations. We conclude that until liver injury, even heavy alcohol drinking has only minor effects on the secretion of gonadotrophins and ovarian steroids. Hypersecretion of PRL and adrenal androgens may well be an initiating mechanism for sexual dysfunction of female alcoholics.

  1. Fluoride exposure changed the structure and the expressions of reproductive related genes in the hypothalamus-pituitary-testicular axis of male mice.

    Science.gov (United States)

    Han, Haijun; Sun, Zilong; Luo, Guangying; Wang, Chong; Wei, Ruifen; Wang, Jundong

    2015-09-01

    Numerous studies have shown that fluoride exposure adversely affected the male reproductive function, while the molecular mechanism is not clear. The present study was to investigate the effects of fluoride exposure (60 days) on the expressions of reproductive related genes, serum sex hormone levels and structures of the hypothalamus-pituitary-testicular axis (HPTA), which plays a vital role in regulating the spermatogenesis in male mice. In this study, 48 male mice were administrated with 0, 25, 50, and 100 mg/L NaF through drinking water. Results showed that the malformation ratio of sperm was significantly increased (Phypothalamus, pituitary and testis were obvious. However, the same fluoride exposure did not lead to significant changes of related mRNA expressions in hypothalamus and pituitary (P>0.05). Also, there were no marked changes in serum hormones. Taken together, we conclude that the mechanism of HPTA dysfunction is mainly elucidated through affecting testes, and its effect on hypothalamus and pituitary was secondary at exposure for 60 days. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Adrenal insufficiency in patients with decompensatedcirrhosis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Adrenal reserve depletion and overstimulation of thehypothalamus-pituitary-adrenal (HPA) axis are causesfor adrenal insufficiency (AI) in critically ill individuals.Cirrhosis is a predisposing condition for AI in cirrhotics aswell. Both stable cirrhotics and liver transplant patients(early and later after transplantation) have been reportedto present AI. The mechanisms leading to reducedcortisol production in cirrhotics are the combination oflow cholesterol levels (the primary source of cortisol), theincreased cytokines production that overstimulate andexhaust HPA axis and the destruction of adrenal glandsdue to coagulopathy. AI has been recorded in 10%-82%cirrhotics depending on the test used to evaluate adrenalfunction and in 9%-83% stable cirrhotics. The similarityof those proportions support the assumption that AI isan endogenous characteristic of liver disease. However,the lack of a gold standard method for AI assessmentand the limitation of precise thresholds in cirrhoticsmake difficult the recording of the real prevalence of AI.This review aims to summarize the present data overAI in stable, critically ill cirrhotics and liver transplantrecipients. Moreover, it provides information about thecurrent knowledge in the used diagnostic tools and thepossible effectiveness of corticosteroids administration incritically ill cirrhotics with AI.

  3. Effect of topiramate and traditional antiepileptic drugs on pituitary-sexual gland axis in adult males with epilepsy

    Institute of Scientific and Technical Information of China (English)

    Fei Xu; Liang Yu; Jie Liu; Yongjie Luo; Hongbin Sun

    2007-01-01

    BACKGROUND: Some reports indicate that traditional antiepileptic drugs can cause a certain effect on reproductive endocrine system in epileptic patients. However, the effect of topiramate on reproductive endocrine system needs to be further studied.OBJECTIVE: To compare the effects of topiramate and traditional valproic acid and carbamazepine on pituitary-sexual gland axis in adult males with epilepsy.DESIGN: Self-contrast and randomly parallel controlled study.SETTING: Sichuan Academy of Medical Sciences (Department of Neurology, Sichuan Provincial People's Hospital).PARTICIPANTS: A total of 54 male epileptic patients aged from 18 to 75 years were selected from Department of Neurology, Sichuan Provincial People's Hospital from January 2004 to June 2006. All patients were diagnosed as epilepsy based on illness history and electroencephalogram (EEG), and types of epilepsy were classified based on the theory of epilepsy and epilepsy syndrome established by International Anti-epilepsy League in 1989 and 2001. The accepted patients and their relatives provided the confirmed consent.METHODS: ① The accepted patients were randomly divided into traditional treatment group [n =26,mean age of (34 ±14) years] and topiramate group [n =28, mean age of (28 ±17) years]. In addition, based on various kinds of drugs, patients in the traditional treatment group were divided into two subgroups,including carbamazepine group (n =14) and valproic acid group (n =12). Patients in both subgroups were respectively treated with carbamazepine (100 mg/table, Shanghai Sanwei Pharmaceutical Factory, batch number: 060705) and valproic acid (200 mg/table, Hunan Xiangzhong Pharmaceutical Co., Ltd., batch number: 061128). Patients in topiramate group were treated with topiramate (25 mg/table, Xi'an Yangsen Pharmaceutical Co., Ltd., batch number: 060215836). Administration: The beginning dosage of topiramate was 25 mg/d, and then increased 25 mg/d per week. The final dosage was 150 mg/d. In

  4. Sensitivity to stress-induced reproductive dysfunction is associated with a selective but not a generalized increase in activity of the adrenal axis.

    Science.gov (United States)

    Herod, S M; Dettmer, A M; Novak, M A; Meyer, J S; Cameron, J L

    2011-01-01

    Stress-induced reproductive dysfunction is a relatively common cause of infertility in women. In response to everyday life stress, some individuals readily develop reproductive dysfunction (i.e., they are stress sensitive), whereas others are more stress resilient. Female cynomolgus monkeys, when exposed to mild combined psychosocial and metabolic stress (change in social environment + 20% reduced calorie diet), can be categorized as stress sensitive (SS; they rapidly become anovulatory in response to stress), medium stress resilient (MSR; they slowly become anovulatory in response to prolonged stress), or highly stress resilient (HSR; they maintain normal menstrual cycles in response to stress). In this study, we examined whether increased sensitivity to stress-induced reproductive dysfunction is associated with elevated adrenal axis activity by measuring 1) the diurnal release of ACTH and cortisol, 2) ACTH and cortisol in response to an acute psychological stress, 3) the percent suppression of cortisol in response to dexamethasone negative feedback, 4) the diurnal release of ACTH and cortisol following exposure to mild psychosocial and metabolic stress, 5) the concentration of cortisol in hair, and 6) adrenal weight. SS monkeys (n = 5) did not differ from MSR (n = 5) or HSR (n = 7) monkeys in any measurement of baseline HPA axis activity or the integrated measurements of chronic HPA axis activity. However, MSR + SS monkeys (n = 10) did secrete more cortisol than HSR monkeys during the daytime hours (1000-1800) following exposure to a novel social environment and reduced diet. We conclude that increased activity of the HPA axis is unlikely to be the primary mechanism causing increased sensitivity to stress-induced reproductive dysfunction.

  5. Longitudinal evaluation of the hypothalamic-pituitary-testicular function in 8 boys with adrenal hypoplasia congenita (AHC due to NR0B1 mutations.

    Directory of Open Access Journals (Sweden)

    Caroline Galeotti

    Full Text Available BACKGROUND: Boys carrying mutations in the NR0B1 gene develop adrenal hypoplasia congenita (AHC and impaired sexual development due to the combination of hypogonadotropic hypogonadism (HH and primary defects in spermatogenesis. METHODS: We analysed the evolution of hypothalamic-pituitary-testicular function of 8 boys with AHC due to NR0B1 mutations. Our objective was to characterize and monitor the progressive deterioration of this function. RESULTS: The first symptoms appeared in the neonatal period (n = 5 or between 6 months and 8.7 years (n = 3. Basal plasma adrenocorticotrophic hormone (ACTH concentrations increased in all boys, whilst cortisol levels decreased in one case. The natremia was equal or below 134 mmol/L and kaliemia was over 5 mmol/L. All had increased plasma renin. In 3 of 4 patients diagnosed in the neonatal period and evaluated during the first year, the basal plasma gonadotropins concentrations, and their response to gonadotropin releasing hormone (GnRH test (n = 2, and those of testosterone were normal. The plasma inhibin B levels were normal in the first year of life. With the exception of two cases these concentrations decreased to below the normal for age. Anti-Müllerian hormone concentrations were normal for age in all except one case, which had low concentrations before the initiation of testosterone treatment. In 3 of the 8 cases the gene was deleted and the remaining 5 cases carried frameshift mutations that are predicted to introduce a downstream nonsense mutation resulting in a truncated protein. CONCLUSIONS: The decreases in testosterone and inhibin B levels indicated a progressive loss of testicular function in boys carrying NR0B1 mutations. These non-invasive examinations can help to estimate the age of the testicular degradation and cryopreservation of semen may be considered in these cases as investigational procedure with the aim of restoring fertility.

  6. Alcohol administration attenuates hypothalamic-pituitary-adrenal (HPA) activity in healthy men at low genetic risk for alcoholism, but not in high-risk subjects.

    Science.gov (United States)

    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.

  7. The Effects of a Korean Ginseng, GINST15, on Hypo-Pituitary-Adrenal and Oxidative Activity Induced by Intense Work Stress.

    Science.gov (United States)

    Flanagan, Shawn D; DuPont, William H; Caldwell, Lydia K; Hardesty, Vincent H; Barnhart, Emily C; Beeler, Matthew K; Post, Emily M; Volek, Jeff S; Kraemer, William J

    2017-10-05

    The effect of GINST15, an enzyme fermented ginseng supplement, on hormonal and inflammatory responses to physical stress in humans is unknown. The purpose of this investigation was to examine the constitutive and stress-induced effects of GINST15 supplement on hypo-pituitary-adrenal (HPA) and antioxidant activity in addition to muscle damage. Ten women (age: 38.7 ± 7.8 years; height: 163.81 ± 4.4 cm; body mass 76.0 ± 11.6 kg) and nine men (age: 41.2. ± 9.7 years; height: 177.4 ± 5.3 cm; body mass: 88.5 ± 5.0 kg) participated in a double-blinded, placebo-controlled, counterbalanced within-group study. Participants completed three 14-day treatment cycles with different doses (high: 960 mg; low: 160 mg; placebo: 0 mg) separated by a 1-week washout period. At the end of treatment, physical stress was imposed with intense resistance exercise work stress. Participants provided blood at rest and various time points after exercise (immediately [IP], 30 min [30], 60 min [60], 24 h [+24HR]). Cortisol (CORT), superoxide dismutase (SOD), total glutathione, nonspecific antioxidant activity, total antioxidant power (TAP), and creatine kinase were measured. GINST15 supplementation produced stress-inducible dose-dependent reductions in circulating cortisol and increased enzymatic and nonspecific antioxidant activity. Twenty-four hours after intense exercise, a high dose GINST15, a bioactive ginsenoside metabolite, significantly reduces muscle damage and HPA responses to physical stress in humans; these effects may result from increased antioxidant expression.

  8. Extensions, Validation, and Clinical Applications of a Feedback Control System Simulator of the Hypothalamo-Pituitary-Thyroid Axis

    Science.gov (United States)

    Samuels, Mary; DiStefano, Joseph J.

    2008-01-01

    sufficient to renormalize average tissue T3 levels and maintain normal TSH, T3, and T4 plasma levels, supporting adequacy of standard L-T4–only treatment. Parenteral T4 administration—TSH, T3, and T4 levels were maintained within normal ranges for all four of these dosing schemes (1× vs. 2× weekly, SC vs. IM), supporting these therapeutic alternatives for patients with compromised L-T4 gut absorption. Central hypothyroidism—These results highlight how highly nonlinear feedback in the hypothalamic-pituitary-thyroid axis acts to maintain normal hormone levels, even with severely reduced TSH secretion. PMID:18844475

  9. The pituitary-bone axis in bone metabolism%骨代谢调控的垂体-骨轴机制

    Institute of Scientific and Technical Information of China (English)

    刘璇; 陆祖宏

    2011-01-01

    近年来,垂体激素包括促甲状腺激素、FSH、促肾上腺皮质激素以及催产素等,相继被发现对骨代谢具有直接的调控作用.这一发现打破了垂体激素是通过作用于靶内分泌腺间接对骨代谢进行调节的传统观念,从而提出了骨代谢调控的垂体-骨轴(pituitary-bone axis)新概念.这些突破性研究进展使人们对垂体激素的功能有了全新的了解,并且对甲亢、绝经、妊娠等引起的骨质疏松症以及糖皮质激素引起的骨坏死的发病机制有了更深的认识,为相关骨代谢疾病的防治以及新药研发提供了新的科学思路和理论基础.%Recent studies have shown that pituitary hormones, including thyroid stimulating hormone (TSH), follicle stimulating hormone(FSH), adrenocorticotropic hormone(ACTH), and oxytocin(OT)may actually bypass their target endocrine organs and affect the skeleton directly. Therefore, a new conception, pituitary-bone axis is proposed. This breakthrough sheds a new light on the function of pituitary hormones and the pathogenesis of osteoporosis associated with hyperthyroidism, menopause or pregnancy, and even osteonecrosis after using glucocorticoids. In addition, it is conducive to give the reference guidance for clinical treatment of metabolic bone diseases and new drug development.

  10. Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat.

    Science.gov (United States)

    Quinn, Matthew; Ueno, Yoshiyuki; Pae, Hae Yong; Huang, Li; Frampton, Gabriel; Galindo, Cheryl; Francis, Heather; Horvat, Darijana; McMillin, Matthew; Demorrow, Sharon

    2012-01-01

    Cholestatic patients often present with clinical features suggestive of adrenal insufficiency. In the bile duct-ligated (BDL) model of cholestasis, the hypothalamic-pituitary-adrenal (HPA) axis is suppressed. The consequences of this suppression on cholangiocyte proliferation are unknown. We evaluated 1) HPA axis activity in various rat models of cholestasis and 2) effects of HPA axis modulation on cholangiocyte proliferation. Expression of regulatory molecules of the HPA axis was determined after BDL, partial BDL, and α-naphthylisothiocyanate (ANIT) intoxication. The HPA axis was suppressed by inhibition of hypothalamic corticotropin-releasing hormone (CRH) expression by central administration of CRH-specific Vivo-morpholinos or by adrenalectomy. After BDL, the HPA axis was reactivated by 1) central administration of CRH, 2) systemic ACTH treatment, or 3) treatment with cortisol or corticosterone for 7 days postsurgery. There was decreased expression of 1) hypothalamic CRH, 2) pituitary ACTH, and 3) key glucocorticoid synthesis enzymes in the adrenal glands. Serum corticosterone and cortisol remained low after BDL (but not partial BDL) compared with sham surgery and after 2 wk of ANIT feeding. Experimental suppression of the HPA axis increased cholangiocyte proliferation, shown by increased cytokeratin-19- and proliferating cell nuclear antigen-positive cholangiocytes. Conversely, restoration of HPA axis activity inhibited BDL-induced cholangiocyte proliferation. Suppression of the HPA axis is an early event following BDL and induces cholangiocyte proliferation. Knowledge of the role of the HPA axis during cholestasis may lead to development of innovative treatment paradigms for chronic liver disease.

  11. Exposure to bleached kraft pulp mill effluent disrupts the pituitary-gonadal axis of white sucker at multiple sites

    Energy Technology Data Exchange (ETDEWEB)

    Van Der Kraak, G.J.; Munkittrick, K.R.; McMaster, M.E.; Portt, C.B.; Chang, J.P. (Department of Zoology, University of Guelph, Ontario (Canada))

    1992-08-01

    Recent studies have demonstrated reproductive problems in white sucker (Catostomus commersoni) exposed to bleached kraft pulp mill effluent (BKME) at Jackfish Bay on Lake Superior. These fish exhibit delayed sexual maturity, reduced gonadal size, reduced secondary sexual characteristics, and circulating steroid levels depressed relative to those of reference populations. The present studies were designed to evaluate sites in the pituitary-gonadal axis of prespawning white sucker affected by BKME exposure. At the time of entry to the spawning stream, plasma levels of immunoreactive gonadotropin (GtH)-II (LH-type GtH) in male and female white sucker were 30- and 50-fold lower, respectively, than the levels in fish from a reference site. A single intraperitoneal injection of D-Arg6, Pro9N-Et sGnRH (sGnRH-A, 0.1 mg/kg) increased plasma GtH levels in male and female fish at both sites, although the magnitude of the response was greatly reduced in BKME-exposed fish. Fish at the BKME site did not ovulate in response to sGnRH-A, while 10 of 10 fish from the reference site ovulated within 6 hr. Plasma 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) levels were depressed in BKME-exposed fish and unlike fish at the reference site, failed to increase in response to sGnRH-A. Testosterone levels in both sexes and 11-ketostestosterone levels in males were elevated in fish from the reference site but were not further increased by GnRH treatment. In contrast, BKME-exposed fish exhibit a transitory increase in testosterone levels in response to the GnRH analog. In vitro incubations of ovarian follicles obtained from fish at the BKME site revealed depressed basal secretion of testosterone and 17,20 beta-P and reduced responsiveness to the GtH analog human chorionic gonadotropin and to forskolin, a direct activator of adenylate cyclase.

  12. Does HPA-Axis Dysregulation Account for the Effects of Income on Effortful Control and Adjustment in Preschool Children?

    Science.gov (United States)

    Lengua, Liliana J.; Zalewski, Maureen; Fisher, Phil; Moran, Lyndsey

    2013-01-01

    The effects of low income on children's adjustment might be accounted for by disruptions to hypothalamic-pituitary-adrenal (HPA)-axis activity and to the development of effortful control. Using longitudinal data and a community sample of preschool-age children (N?=?306, 36-39?months) and their mothers, recruited to over-represent low-income…

  13. Gonadal and Adrenal Abnormalities in Drug Users: Cause or Consequence of Drug Use Behavior and Poor Health Outcomes

    Directory of Open Access Journals (Sweden)

    Todd T. Brown

    2006-01-01

    Full Text Available Opiates and cocaine both have effects on adrenal and gonadal function. Opiates suppress the hypothalamic-pituitary adrenal (HPA axis, whereas cocaine leads to HPA activation. Opiates also cause gonadal dysfunction in both men and women. During withdrawal from opiates and cocaine, the HPA axis is activated which may reinforce relapse behavior. This review describes these hormonal effects and explores the potential consequences, including the effects on mood cognition and cardiovascular risk. Modification of the drug-induced hormonal dysfunction may represent a treatment strategy for drug rehabilitation.

  14. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Senderovitz, Thomas

    2007-01-01

    for the population PK/PD data analysis. A systematic population PK/PD model-building framework using stochastic differential equations was applied to the data to identify nonlinear dynamic dependencies and to deconvolve the functional feedback interactions of the HPG axis. Results In our final PK/PD model of the HPG......Aims To develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic-pituitary-gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin...... for the different dynamic responses observed after administration of both GnRH agonists and GnRH receptor blockers, suggesting that the model adequately characterizes the underlying physiology of the endocrine system....

  15. Impairment of the cortisol stress response mediated by the hypothalamus-pituitary-interrenal (HPI) axis in zebrafish (Danio rerio) exposed to monocrotophos pesticide.

    Science.gov (United States)

    Zhang, Xiaona; Zhong, Yan; Tian, Hua; Wang, Wei; Ru, Shaoguo

    2015-01-01

    In teleosts, an important component of the stress response is coordinated by the hypothalamic-pituitary-interrenal (HPI) axis. Environmental contaminants might disrupt the stress axis and consequently affect the stress response in fish. To investigate the effect of monocrotophos (MCP) pesticide on the stress response of fish and its potential mechanisms, adult zebrafish (Danio rerio) were exposed to 0, 1, 10, and 100μg/L of a 40% MCP-based pesticide for 21d, after which time fish were subjected to a 3-min air-exposure stressor. Concentrations of the whole-body cortisol were measured by radioimmunoassay and abundances of transcripts of proteins involved in the HPI axis were determined using quantitative real-time PCR. Results showed that 100μg/L of MCP pesticide decreased whole-body cortisol levels of female zebrafish in response to an acute stressor, but without any effect on the cortisol response in males. 100μg/L MCP pesticide reduced POMC and GR expression in the brain, MC2R and P45011β expression in the head kidney, but enhanced 20β-HSD2 expression in the head kidney, suggesting that MCP damaged the HPI axis involving acting at pituitary regulatory levels, inhibiting cortisol synthesis and stimulating cortisol catabolism, or disturbing the negative feedback regulation. Additionally, MCP depressed liver GR transcription but did not affect phosphoenolpyruvate carboxykinase and tyrosine aminotransferase expression in zebrafish, suggesting a role for this pesticide in reducing target tissue responsiveness to cortisol. Considered together, the reduced ability to elevate cortisol levels in response to an acute stress may be an endocrine dysfunction occurring in zebrafish subchronically exposed to MCP pesticide.

  16. Identification of human GnIH homologs, RFRP-1 and RFRP-3, and the cognate receptor, GPR147 in the human hypothalamic pituitary axis.

    Directory of Open Access Journals (Sweden)

    Takayoshi Ubuka

    Full Text Available The existence of a hypothalamic gonadotropin-inhibiting system has been elusive. A neuropeptide named gonadotropin-inhibitory hormone (GnIH, SIKPSAYLPLRF-NH(2 which directly inhibits gonadotropin synthesis and release from the pituitary was recently identified in quail hypothalamus. Here we identify GnIH homologs in the human hypothalamus and characterize their distribution and biological activity. GnIH homologs were isolated from the human hypothalamus by immunoaffinity purification, and then identified as MPHSFANLPLRF-NH(2 (human RFRP-1 and VPNLPQRF-NH(2 (human RFRP-3 by mass spectrometry. Immunocytochemistry revealed GnIH-immunoreactive neuronal cell bodies in the dorsomedial region of the hypothalamus with axonal projections to GnRH neurons in the preoptic area as well as to the median eminence. RT-PCR and subsequent DNA sequencing of the PCR products identified human GnIH receptor (GPR147 mRNA expression in the hypothalamus as well as in the pituitary. In situ hybridization further identified the expression of GPR147 mRNA in luteinizing hormone producing cells (gonadotropes. Human RFRP-3 has recently been shown to be a potent inhibitor of gonadotropin secretion in cultured sheep pituitary cells by inhibiting Ca(2+ mobilization. It also directly modulates GnRH neuron firing. The identification of two forms of GnIH (RFRP-1 and RFRP-3 in the human hypothalamus which targets human GnRH neurons and gonadotropes and potently inhibit gonadotropin in sheep models provides a new paradigm for the regulation of hypothalamic-pituitary-gonadal axis in man and a novel means for manipulating reproductive functions.

  17. The Effects of Hydroalcoholic Extract of Matricaria Recutita on the Hormonal Pituitary-Testis Axis and Testis Tissue Changes of Mature Male Rats

    Directory of Open Access Journals (Sweden)

    Laili Hatami

    2013-06-01

    Full Text Available Background & Objectives: Matricaria recutita is one of the most ancient and well- known medicinal plants, and its role in the treatment of a wide range of diseases has been studied . The purpose of this study was to investigate the effect of Matricaria recutita on spermatogenesis and the pituitary-gonadal axis in male adult rats.   Materials & Methods: In this experimental study, the animals were divided into two groups: the control group, which received 1 ml of distilled water orally, and the experimental group, which received 100 mg/kg of Matricaria recutita extract via gavage feeding once daily for an 8-week period. After the treatment period, several fertility indices such as the weight of the reproductive organs, sperm count, sperm motility and vitality, and testis histological changes as well as blood serum levels of testosterone, estrogen, FSH, and LH were measured.   Results: Our statistical analysis showed a significant increase in the weight of the reproductive organs, sperm count, and blood testosterone in the group which received 100 mg/kg of Matricaria recutita hydroalcholic extract .   Conclusion: The results of this study demonstrated that hydroalcholic extract of Matricaria recutita could increase the function of the hormonal pituitary-testis axis and spermatogenesis in male rats.  

  18. Effects of aqueous extract from Asparagus officinalis L. roots on hypothalamic-pituitary-gonadal axis hormone levels and the number of ovarian follicles in adult rats

    Directory of Open Access Journals (Sweden)

    Hojatollah Karimi Jashni

    2016-02-01

    Full Text Available Background: Asparagus is a plant with high nutritional, pharmaceutical, and industrial values. Objective: The present study aimed to evaluate the effect of aqueous extract of asparagus roots on the hypothalamic-pituitary-gonadal axis hormones and oogenesis in female rats. Materials and Methods: In this experimental study, 40 adult female Wistar rats were divided into five groups, which consist 8 rats. Groups included control, sham and three experimental groups receiving different doses (100, 200, 400 mg/kg/bw of aqueous extract of asparagus roots. All dosages were administered orally for 28 days. Blood samples were taken from rats to evaluate serum levels of Gonadotropin releasing hormone (GnRH, follicular stimulating hormone (FSH, Luteinal hormone (LH, estrogen, and progesterone hormones. The ovaries were removed, weighted, sectioned, and studied by light microscope. Results: Dose-dependent aqueous extract of asparagus roots significantly increased serum levels of GnRH, FSH, LH, estrogen, and progestin hormones compared to control and sham groups. Increase in number of ovarian follicles and corpus luteum in groups treated with asparagus root extract was also observed (p<0.05. Conclusion: Asparagus roots extract stimulates secretion of hypothalamic- pituitary- gonadal axis hormones. This also positively affects oogenesis in female rats.

  19. Cognition and HPA axis reactivity in mildly to moderately depressed outpatients. A case-control study

    DEFF Research Database (Denmark)

    Krogh, Jesper; Videbech, Poul; Renvillard, Signe Groth

    2012-01-01

    Background: Patients with depression display neurobiological changes of the hypothalamic-pituitary axis as well as cognitive disturbances. Aims: To assess any association between hypothalamus-pituitary-adrenal (HPA) axis reactivity and memory-related cognitive functions. Methods: Depressed......, a positive association between post-DST cortisol and Rey's Complex figure test (1.3; 95% CI 0.3-3.6; P =¿0.02) was found. We found no significant associations between other memory functions and cortisol measures. Conclusions: Contrary to our hypothesis, we found a positive association between cortisol levels...

  20. Adrenal Insufficiency - Aetiology, Diagnosis and Treatment

    Directory of Open Access Journals (Sweden)

    Nazma Akter

    2015-03-01

    Full Text Available Adrenal insufficiency is caused by either primary adrenal failure or by hypothalamic-pituitary impairment of the corticotropic axis. Adrenal insufficiency, first codified in 1855 by Thomas Addison, remains relevant in 2014 because of its lethal nature. Though, it is a rare disease but is life threatening when overlooked. Main presenting symptoms such as fatigue, anorexia and weight loss are nonspecific, thus diagnosis is often delayed. The diagnostic work-up is well established but some pitfalls remain. The diagnosis is adequately established by the 250 μg ACTH (adrenocorticotropic hormone stimulation test in most cases. Glucocorticoids provide life saving treatment but long-term quality of life is impaired, perhaps because therapy is not given in a physiologic way. Dehydroepiandrosterone-replacement therapy has been introduced that could help to restore quality of life. It may be useful in pubertal girls, but not in adults. Monitoring of glucocorticoid-replacement is difficult due to lack of objective methods of assessment and is therefore largely based on clinical grounds. Thus, long-term management of patients with adrenal insufficiency remains a challenge, requiring an experienced specialist.

  1. 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.

  2. Identification of an endocannabinoid system in the rat pars tuberalis-a possible interface in the hypothalamic-pituitary-adrenal system?

    Science.gov (United States)

    Jafarpour, Arsalan; Dehghani, Faramarz; Korf, Horst-Werner

    2017-04-01

    Endocannabinoids (ECs) are ubiquitous endogenous lipid derivatives and play an important role in intercellular communication either in an autocrine/paracrine or in an endocrine fashion. Recently, an intrinsic EC system has been discovered in the hypophysial pars tuberalis (PT) of hamsters and humans. In hamsters, this EC system is under photoperiodic control and appears to influence the secretion of hormones such as prolactin from the adenohypophysis. We investigate the EC system in the PT of the rat, a frequently used species in endocrine research. By means of immunocytochemistry, enzymes involved in EC biosynthesis, e.g., N-arachidonoyl-phosphatidylethanolamine-phospholipase D (NAPE-PLD) and diacylglycerol lipase α (DAGLα) and enzymes involved in EC degradation, e.g., fatty acid amide hydrolase (FAAH) and cyclooxygenase-2 (COX-2), were demonstrated in PT cells of the rat. Immunoreactions (IR) for FAAH and for the cannabinoid receptor CB1 were observed in corticotrope cells of the rat adenohypophysis; these cells were identified by antibodies against proopiomelanocortin (POMC) or adrenocorticotrophic hormone (ACTH). In the outer zone of the median eminence, numerous nerve fibers and terminals displayed CB1 IR. The majority of these were also immunolabeled by an antibody against corticotropin-releasing factor (CRF). These results suggest that the EC system at the hypothalamo-hypophysial interface affects both the CRF-containing nerve fibers and the corticotrope cells in the adenohypophysis. Our data give rise to the hypothesis that, in addition to its well-known role in the reproductive axis, the PT might influence adrenal functions and, thus, the stress response and immune system.

  3. Feeding prepubescent gilts a high-fat diet induces molecular changes in the hypothalamus-pituitary-gonadal axis and predicts early timing of puberty.

    Science.gov (United States)

    Zhuo, Yong; Zhou, Dongsheng; Che, Lianqiang; Fang, Zhengfeng; Lin, Yan; Wu, De

    2014-01-01

    The onset of puberty in females has been occurring earlier over the past decades, presumably as a result of improved nutrition in developed countries. However, the underlying molecular mechanisms responsible for the early attainment of puberty as a result of nutrition fortification remain largely unknown. The aim of this study was to evaluate the hormone and gene expression changes in prepubescent gilts fed a high-fat diet to investigate whether these changes could predict the early timing of puberty. Forty gilts were fed a daily basal diet (LE) or a basal diet with an additional 270 g/d or 340 g/d of fat (HE) during the prepubescent phase. Blood samples were collected during the prepubescent phase to detect hormone secretion changes in insulin-like growth factor-1, kisspeptin, estradiol, progesterone, and leptin. The gene expressions at the hypothalamus-pituitary-gonadal axis were examined on day 73 of the experiment (average age on day 177) during the prepubescent phase. An HE diet resulted in accelerated body weight gain and back-fat thickness at the P2 point compared with LE gilts during the prepubescent phase. Gilts that were fed HE diets attained puberty 12 d earlier than LE gilts, and a larger proportion of HE gilts reached puberty at day 180 or 190 of age. A postmortem analysis revealed a promoted development of the uterus and ovary tissue that was characterized by a 53.7% and 29.5% increase in the uterine and ovary weight, respectively, and an increased length of the uterine horn and oviduct tissue in HE gilts. Real-time quantitative polymerase chain reaction revealed that HE gilts had higher Kiss-1, G protein-coupled receptor 54, gonadotropin-releasing hormone and estrogen receptor α mRNA expression levels in the hypothalamic anteroventral periventricular nucleus; the leptin receptor mRNA expression level was higher in the hypothalamic arcuate nucleus and ovary tissue; the insulin-like growth factor-1 receptor expression was higher in the pituitary and

  4. HPA-axis activity and externalizing behavior problems in early adolescents from the general population : the role of comorbidity and gender The TRAILS study

    NARCIS (Netherlands)

    Marsman, Rianne; Swinkels, Sophie H. N.; Rosmalen, Judith G. M.; Oldehinkel, Albertine J.; Ormel, Johan; Buitelaar, Jan K.

    2008-01-01

    Contradictory findings on the relationship between hypothalamus-pituitary-adrenal (HPA)-axis activity and externalizing behavior problems could be due to studies not accounting for issues of comorbidity and gender. In a population-based cohort of 1768 (10- to 12-year-old) early adolescents, we used

  5. Effects of ethanolic leaf extract of Spondias mombin on the pituitary-gonadal axis of female Wistar rats

    Institute of Scientific and Technical Information of China (English)

    Asuquo OR; Oko OOK; Brownson ES; Umoetuk GB; Utin IS

    2013-01-01

    Objective: To determine the effects of ethanolic leaf extract of Spondias mombin (S. mombin) on the histology of the anterior pituitary, ovary and uterus; and on the serum sex hormones of adult female Wistar rats. Methods: Twenty-four female Wistar rats were randomly assigned into four groups of six rats per group. The animals in the treatment groups were administered orally ethanolic extract of S. mombin leaves at the doses of 250, 350 and 500 mg/kg body weight daily for fourteen days. Rats in the control group received distilled water. The body weights of the rats were determined at the beginning and end of the experiment. Histological analysis of pituitary, ovary and uterus was carried out. Hormonal assay for estrogen, progesterone, FSH and LH were done using Enzyme-Linked Immunoabsorbent Assay (ELISA). Results: There was significant (P<0.05) decrease in relative organ weights of extract-treated rats compared to the control. Pituitary showed accumulation and aggregation of cells in experimental animals. Uteri of treated groups showed thickening of endometrial lining and presence of cysts, ovarian tissues were damaged. Furthermore, the extract caused reduction in serum concentration of sex hormones of the treated animals relative to the control. Conclusion: This study suggests that ethanolic extract of S. mombin leaf may have antifertility property, confirming its use as a local contraceptive.

  6. Psychobiological mechanisms underlying the social buffering of the hypothalamic-pituitary-adrenocortical axis: a review of animal models and human studies across development.

    Science.gov (United States)

    Hostinar, Camelia E; Sullivan, Regina M; Gunnar, Megan R

    2014-01-01

    Discovering the stress-buffering effects of social relationships has been one of the major findings in psychobiology in the last century. However, an understanding of the underlying neurobiological and psychological mechanisms of this buffering is only beginning to emerge. An important avenue of this research concerns the neurocircuitry that can regulate the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. The present review is a translational effort aimed at integrating animal models and human studies of the social regulation of the HPA axis from infancy to adulthood, specifically focusing on the process that has been named social buffering. This process has been noted across species and consists of a dampened HPA axis stress response to threat or challenge that occurs with the presence or assistance of a conspecific. We describe aspects of the relevant underlying neurobiology when enough information exists and expose major gaps in our understanding across all domains of the literatures we aimed to integrate. We provide a working conceptual model focused on the role of oxytocinergic systems and prefrontal neural networks as 2 of the putative biological mediators of this process, and propose that the role of early experiences is critical in shaping later social buffering effects. This synthesis points to both general future directions and specific experiments that need to be conducted to build a more comprehensive model of the HPA social buffering effect across the life span that incorporates multiple levels of analysis: neuroendocrine, behavioral, and social.

  7. Diclofenac can exhibit estrogenic modes of action in male Xenopus laevis, and affects the hypothalamus-pituitary-gonad axis and mating vocalizations.

    Science.gov (United States)

    Efosa, Norah Johanna; Kleiner, Wibke; Kloas, Werner; Hoffmann, Frauke

    2017-04-01

    Diclofenac (DCF) is a non-steroidal analgesic and antiphlogistic. Due to its tremendous use, DCF can be found in the environment, especially in sewage, but also surface waters, ground and drinking water. Previous studies indicated that DCF can modulate the reproductive physiology of fish by altering the expression of important key enzymes of the hypothalamus-pituitary-gonad-axis (HPG-axis) and might act as an estrogenic endocrine disrupting chemical (EDC). Other studies, however, demonstrated that DCF does not exhibit any estrogenicity. Thus, in the present study we investigated whether an exposure to DCF can affect reproductive behavior and physiology of adult male X. laevis by analyzing DCF effects on the mate calling behavior of the frogs and on gene expression patterns of key biomarkers of the HPG-axis. In addition, plasma sex steroid levels were determined to gain detailed insights into the mechanisms of DCF action. We could demonstrate that DCF can act as EDC by exhibiting slight estrogenic modes of action. In addition, pharmacological impacts on gonadal steroidogenesis could be revealed leading to imbalances in sex steroid levels and ratios. DCF furthermore altered the calling behavior of exposed males, potentially reducing the mating and reproductive success of the frogs, possibly leading to severe population effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Hypothalamus-pituitary-thyroid axis disruption in rats with breast cancer is related to an altered endogenous oxytocin/insulin-regulated aminopeptidase (IRAP) system.

    Science.gov (United States)

    Carrera-González, María Pilar; Ramírez-Expósito, María Jesús; de Saavedra, Jose Manuel Arias; Sánchez-Agesta, Rafael; Mayas, María Dolores; Martínez-Martos, Jose Manuel

    2011-06-01

    Associations of breast cancer with diseases of the thyroid have been repeatedly reported, but the mechanism underlying this association remains to be elucidated. It has been reported that oxytocin (OXT) attenuates the thyroid-stimulating hormone (TSH) release in response to thyrotrophin-releasing hormone (TRH) and decreased plasma levels of TSH as well as the thyroid hormones by an effect mediated by the central nervous system. Oxytocinase (IRAP) is the regulatory proteolytic enzyme reported to hydrolyze OXT. Changes in IRAP activity have been reported in both human breast cancer and N-methyl-nitrosourea (NMU)-induced rat mammary tumours. Here, we measure IRAP activity fluorometrically using cystyl-β-naphthylamide as the substrate, in the hypothalamus-pituitary-thyroid axis together with the circulating levels of OXT, and its relationship with circulating levels of TSH and free thyroxine (fT4), as markers of thyroid function in control rats and rats with breast cancer induced by NMU. We found decreased thyroid function in rats with breast cancer induced by NMU, supported by the existence of lower serum circulating levels of both TSH and fT4 than their corresponding controls. Concomitantly, we found a decrease of hypothalamic IRAP activity and an increase in circulating levels of OXT. We propose that breast cancer increases OXT pituitary release by decreasing its hypothalamic catabolism through IRAP activity, probably due to the alteration of the estrogenic endocrine status. Thus, high circulating levels of OXT decreased TSH release from the pituitary, and therefore, of thyroid hormones from the thyroid, supporting the association between breast cancer and thyroid function disruption.

  9. Feedback inhibition of gonadotropins by testosterone in men with hypogonadotropic hypogonadism: comparison to the intact pituitary-testicular axis in primary hypogonadism.

    Science.gov (United States)

    Shimon, Ilan; Lubina, Alexandra; Gorfine, Malka; Ilany, Jacob

    2006-01-01

    Men with hypogonadotropic hypogonadism (HH) due to hypothalamic-pituitary disease present with low serum testosterone levels combined with undetectable, low, or normal gonadotropin levels. Treatment consists of testosterone replacement to reverse the symptoms of androgen deficiency. The aim of this study was to examine the dynamics and feedback inhibition of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in relation to testosterone in 38 men with HH treated with testosterone. Findings were compared with 11 men with primary hypergonadism (PH). Testosterone replacement led to a suppression of FSH levels from 2.8 IU/L at baseline to 1.1 IU/L and to a suppression of LH levels from 2.3 to 0.8 IU/L. There was a linear correlation between levels of FSH and LH (after natural log transformation for both) and testosterone levels in both the HH and PH groups. However, the differences in intercepts and slopes between the groups were significant. To determine whether nonsuppressed FSH or LH during testosterone replacement reduces the probability of eugonadism, as reflected by normal testosterone levels, gonadotropin levels were measured and categorized as low (2 IU/L). The higher FSH or LH levels were found to significantly decrease the chance for achieving eugonadism. In conclusion, in men with HH due to hypothalamic-pituitary disease or injury, the pituitary-testicular hormonal axis maintains its physiological negative feedback between testosterone and gonadotropins. Thus, gonadotropin levels in men with HH might be useful, together with testosterone concentrations, for assessing the adequacy of androgen replacement.

  10. A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Xu, D. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Qin, J. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhang, C. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Chen, L.B. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, J. [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, H., E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2012-11-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

  11. Expression and localization of IL-18 in the hypothalamic-pituitary-ovarian axis of non-pregnant, pregnant, and abortive rats.

    Science.gov (United States)

    Wang, Yuesi; Zhang, Xiuli; Zhang, Yan; Xu, Hui; Fang, Guangli

    2011-12-01

    Cytokines present in the reproductive system play an important role both in the modulation of immune responses to infectious challenge and in the establishment and maintenance of pregnancy. Interleukin 18 (IL-18) has been regarded as an important regulator of innate and acquired immune response, but its expression and distribution in the hypothalamic-pituitary-ovarian axis remain unclear. In this paper, the expression and distribution of IL-18 in non-pregnant, pregnant, and early abortive rats were examined using an ultra-sensitive immunohistochemical streptavidin-peroxidase method, enzyme-linked immunosorbent assay, and reverse transcription-polymerase chain reaction. The results showed that IL-18 expression in the pituitary, in follicular ovaries, and in the corpus luteum of abortive rats were significantly lower than that of pregnant and non-pregnant rats. However, the staining of IL-18 in the hypothalamus, interstitial glands of the ovary, and uterus of abortive rats was strikingly stronger than those of the non-pregnant ones. IL-18 mRNA expression in rat uterus was detected in all groups, whereas IL-18 mRNA content in abortive rat uterus was significantly higher than in normal pregnant rats. Further, IL-18 in the peripheral blood serum of abortive rats was significantly lower than in same-period normal pregnant rats. The differential expression of IL-18 in early abortion suggests that IL-18 may be related to the underlying mechanisms of abortion.

  12. Development of Thyroid Gland Specific Markers of Hypothalamic-pituitary-thyroid Axis Disruption in the Amphibian Model Species Xenopus laevis

    Science.gov (United States)

    The focus of the research presented here is the development of an in vitro thyroid gland culture system to test the effect of chemicals directly on the gland without influence of other parts of the HPT axis.

  13. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues

    DEFF Research Database (Denmark)

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Senderovitz, Thomas;

    2007-01-01

    Aims To develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic-pituitary-gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin...... and the GnRH receptor blocker degarelix. Methods Fifty-eight healthy subjects received single subcutaneous or intramuscular injections of 3.75 mg of triptorelin and 170 prostate cancer patients received multiple subcutaneous doses of degarelix of between 120 and 320 mg. All subjects were pooled...... for the different dynamic responses observed after administration of both GnRH agonists and GnRH receptor blockers, suggesting that the model adequately characterizes the underlying physiology of the endocrine system....

  14. Suppression of the brain-pituitary-testicular axis function following acute arsenic and manganese co-exposure and withdrawal in rats.

    Science.gov (United States)

    Adedara, Isaac A; Abolaji, Amos O; Awogbindin, Ifeoluwa O; Farombi, Ebenezer O

    2017-01-01

    Despite the fact that most environmental exposures to metals do not occur in isolation, the combined effects of metal mixtures on brain-pituitary-gonadal axis are poorly known. The present study investigated the impacts of co-exposure to arsenic (As) and manganese (Mn) on sperm characteristics, reproductive hormones and selected oxidative stress indices in the brain, testes and epididymis of rats following exposure for 15 consecutive days to 60mg/L of AsO2Na and 30mg/L of MnCl2 in drinking water. The results showed that while the brain weight remained unaffected, the fluid intake and the weights of testes and epididymis significantly (prats. Moreover, the significant decreases in the antioxidant status in brain, testes and epididymis as well as in the circulatory concentrations of follicle-stimulating hormone, luteinizing hormone and testosterone were similar following separate or combined exposure of rats to As and Mn. The marked oxidative damage in the investigated tissues was accompanied by a significant decrease in the sperm quantity and quality in all the treated rats when compared with the control. Interestingly, most of the parameters determined immediately after the exposure period persisted in rats from the withdrawal experiment. Collectively, co-exposure to As and Mn suppressed the brain-pituitary-testicular axis function and the post-testicular events such as sperm function possibly via a mechanism involving persistent oxidative stress and endocrine disruption in the exposed rats. Copyright © 2016 Elsevier GmbH. All rights reserved.

  15. Familial longevity is not associated with major differences in the hypothalamic-pituitary-gonadal axis in healthy middle-aged men

    Directory of Open Access Journals (Sweden)

    Evie van der Spoel

    2016-11-01

    Full Text Available Context: A trade-off between fertility and longevity possibly exists. The association of the male hypothalamic-pituitary-gonadal (HPG axis with familial longevity has not yet been investigated.Objective: To study 24h hormone concentration profiles of the HPG axis in men enriched for familial longevity and controls. Design: We frequently sampled blood over 24 hours in 10 healthy middle-aged male offspring of nonagenarian participants from the Leiden Longevity Study together with 10 male age-matched controls. Individual 24h luteinizing hormone (LH and testosterone concentration profiles were analysed by deconvolution analyses to estimate secretion parameters. Furthermore, the temporal relationship between LH and testosterone was assessed by cross-correlation analysis. We used (cross- approximate entropy to quantify the strength of feedback and/or feedforward control of LH and testosterone secretion.Results: Mean (95% confidence interval (CI total LH secretion of the offspring was 212 (156–268 U/L/24h, which did not differ significantly (p=0.51 from the total LH secretion of controls (186 (130–242 U/L/24h. Likewise, mean (95% CI total testosterone secretion of the offspring (806 (671–941 nmol/L/24h and controls (811 (676–947 nmol/L/24h were similar (p=0.95. Other parameters of LH and testosterone secretion were also not significantly different between offspring and controls. The temporal relationship between LH and testosterone and the strength of feedforward/feedback regulation within the HPG axis were similar between offspring of long-lived families and controls. Conclusions: This relatively small study suggests that in healthy male middle-aged participants, familial longevity is not associated with major differences in the HPG axis. Selection on both fertility and health may in part explain for the results.

  16. The postprandial rise in plasma cortisol in men is mediated by macronutrient-specific stimulation of adrenal and extra-adrenal cortisol production.

    Science.gov (United States)

    Stimson, Roland H; Mohd-Shukri, Nor A; Bolton, Jennifer L; Andrew, Ruth; Reynolds, Rebecca M; Walker, Brian R

    2014-01-01

    Circadian variation is a fundamental characteristic of plasma glucocorticoids, with a postprandial rise in cortisol an important feature. The diurnal rhythm is presumed to reflect alterations in hypothalamic-pituitary-adrenal axis activity; however, cortisol is produced not only by the adrenal glands but also by regeneration from cortisone by the enzyme 11β-hydroxysteroid dehydrogenase type 1, mainly in liver and adipose tissue. We tested the contribution of peripheral cortisol regeneration to macronutrient-induced circadian variation of plasma cortisol in humans. This was a randomized, single-blinded, crossover study. The study was conducted at a hospital research facility. Eight normal-weight healthy men participated in the study. Subjects were given isocaloric energy isodense flavor-matched liquid meals composed of carbohydrate, protein, fat, or low-calorie placebo during infusion of the stable isotope tracer 9,11,12,12-[2H]4-cortisol. Plasma cortisol increased similarly after all macronutrient meals (by ∼90 nmol/L) compared with placebo. Carbohydrate stimulated adrenal secretion and extra-adrenal regeneration of cortisol to a similar degree. Protein and fat meals stimulated adrenal cortisol secretion to a greater degree than extra-adrenal cortisol regeneration. The increase in cortisol production by 11β-hydroxysteroid dehydrogenase type 1 was in proportion to the increase in insulin. The postprandial cortisol rise was not accounted for by decreased cortisol clearance. Food-induced circadian variation in plasma cortisol is mediated by adrenal secretion and extra-adrenal regeneration of cortisol. Given that the latter has the more potent effect on tissue cortisol concentrations and that effects on adrenal and extra-adrenal cortisol production are macronutrient specific, this novel mechanism may contribute to the physiological interplay between insulin and glucocorticoids and the contrasting effects of certain diets on postprandial metabolism.

  17. Mimecan in pituitary corticotroph cells may regulate ACTH secretion and the HPAA.

    Science.gov (United States)

    Ma, Qin-Yun; Zhang, Xiao-Na; Jiang, He; Wang, Zhi-Quan; Zhang, Hui-Jie; Xue, Li-Qiong; Chen, Ming-Dao; Song, Huai-Dong

    2011-07-20

    Mimecan is a protein of unknown function that is expressed in the pituitary tissues of mouse and human. In this study, we observed the function of mimecan on the proopiomelanocortin (POMC) gene in the pituitary and the hypothalamo-pituitary-adrenal axis (HPAA). Incubating pituitary corticotroph AtT-20 cells with recombinant mimecan protein stimulated adrenocorticotrophic hormone (ACTH) secretion without significantly up-regulating POMC gene expression. In addition, pituitary corticotroph AtT-20 cell corticotropin-releasing hormone receptor 1 (CRHR1) gene expression was induced by mimecan. Interestingly, long-term mimecan overexpression in corticotroph cells increased CRHR1 mRNA levels while slightly decreasing POMC mRNA expression and ACTH secretion. Using mimecan knockout mice, we found that, although the serum ACTH concentration was not significantly different between wild type and mimecan knockout mice under basal conditions, the serum ACTH level was relatively lower in mimecan knockout mice after treatment with corticotropin-releasing hormone (CRH). Meanwhile, we observed that POMC and CRHR1 gene expression decreased in primary cultured knockout mouse pituitary cells compared with wild type cells. Taken together, these data suggest that mimecan expressed in pituitary corticotroph cells mainly regulates ACTH secretion in the pituitary and coordinates the HPAA. Copyright © 2011. Published by Elsevier Ireland Ltd.

  18. [Ultrasound evaluation of fetal adrenal gland volume. The role of fetal adrenal glands in the pathogenesis of preterm labor].

    Science.gov (United States)

    Krzyzanowski, Arkadiusz; Karwasik-Kajszczarek, Katarzyna; Dymanowska-Dyjak, Izabela; Kondracka, Adrianna; Kwaśniewska, Anna

    2014-02-01

    Preterm labor remains to be one of the most important challenges of contemporary perinatology and constitutes the main reason of perinatal mortality and prematurity of neonates. Studies on preterm labor have confirmed the mutual interactions of several different hormonal systems while the activation of hypothalamic- pituitary- adrenal axis seems to have the greatest influence. It has been also suggested that size and mass of fetal adrenal glands may be associated with the risk of preterm labor. Several authors have shown that the evaluation of fetal adrenal gland volume may be a useful marker of fetal growth during pregnancy. Technological advancements enabled the development of three-dimensional ultrasound evaluation (3D) of the fetal adrenal glands, facilitating a more precise evaluation of their volume. Also, it seems to have higher sensitivity and specificity than two-dimensional ultrasonography (2D). Studies have confirmed a direct relationship between fetal adrenal gland size and the onset of preterm labor within at least 1 week since the ultrasound exam. They have also suggested that in a physiological pregnancy the relation between fetal zone and the whole organ remains constant throughout the pregnancy. Disruption of these proportions and fetal zone enlargement are considered to be a marker of labor cascade and preterm labor with significantly higher sensitivity and specificity than ultrasound evaluation of the cervical length and assessment of the fetal fibronectin concentration.

  19. A Comparative Study of Pituitary Volume Variations in MRI in Acute Onset of Psychiatric Conditions.

    Science.gov (United States)

    Soni, Brijesh Kumar; Joish, Upendra Kumar; Sahni, Hirdesh; George, Raju A; Sivasankar, Rajeev; Aggarwal, Rohit

    2017-02-01

    The growing belief that endocrine abnormalities may underlie many mental conditions has led to increased use of imaging and hormonal assays in patients attending to psychiatric OPDs. People who are in an acute phase of a psychiatric disorder show Hypothalamic Pituitary Adrenal (HPA) axis hyperactivity, but the precise underlying central mechanisms are unclear. To assess the pituitary gland volume variations in patients presenting with new onset acute psychiatric illness in comparison with age and gender matched controls by using MRI. The study included 50 patients, with symptoms of acute psychiatric illness presenting within one month of onset of illness and 50 age and gender matched healthy controls. Both patients and controls were made to undergo MRI of the Brain. A 0.9 mm slices of entire brain were obtained by 3 dimensional T1 weighted sequence. Pituitary gland was traced in all sagittal slices. Anterior pituitary and posterior pituitary bright spot were measured separately in each slice. Volume of the pituitary (in cubic centimetre- cm(3)) was calculated by summing areas. Significance of variations in pituitary gland volumes was compared between the cases and controls using Analysis of Covariance (ANOVA). There were significantly larger pituitary gland volumes in the cases than the controls, irrespective of psychiatric diagnosis (ANOVA, f=15.56; p=0.0002). Pituitary volumes in cases were 15.36% (0.73 cm(3)) higher than in controls. There is a strong likelihood of HPA axis overactivity during initial phase of all mental disorders along with increased pituitary gland volumes. Further studies including hormonal assays and correlation with imaging are likely to provide further insight into neuroanatomical and pathological basis of psychiatric disorders.

  20. Temporal changes of the adrenal endocrine system in a restraint stressed mouse and possibility of postmortem indicators of prolonged psychological stress.

    Science.gov (United States)

    Hayashi, Takahito; Ikematsu, Kazuya; Abe, Yuki; Ihama, Yoko; Ago, Kazutoshi; Ago, Mihoko; Miyazaki, Tetsuji; Ogata, Mamoru

    2014-07-01

    We investigated temporal changes of adrenal endocrine systems through the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenomedullary (SA) axis in restraint stressed mice. Restraint stress for 1 day to 3 weeks caused a significant increase in serum levels of ACTH and glucocorticoids accompanied with an increase in adrenal weights, indicating activation of the HPA axis. Reflecting the overproduction of glucocorticoids, adrenal cholesterol content decreased. Moreover, adrenal gene expression involved in cholesterol supply, including scavenger receptor-class B type I, HMG-CoA reductase, and hormone-sensitive lipase, was increased over the same period. After 4 weeks stress, all of these changes returned to control levels. In contrast, adrenal gene expression of chromogranin A, which is cosecreted with catecholamine via the SA axis, was increased with 1 day to 2 weeks of stress, and decreased with 3-4 weeks of stress. Our results suggest that analyses of adrenal endocrine systems based on the combination of several markers examined here would be useful for not only proving prolonged psychological stress experience but also determining its duration.

  1. Effects of hypophysectomy and administration of pituitary hormones on luteal function and uptake of high density lipoproteins by luteinized ovaries and adrenals of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, B.D.; Rajkumar, K.; McKibbin, P.E.; Macdonald, G.J.; Buhr, M.M.; Grinwich, D.L.

    1985-04-01

    The role of plasma lipoproteins and hypophyseal hormones in the maintenance of progesterone secretion by the rat corpus luteum was investigated. In the first experiment, rats were treated daily from days 1-6 of pregnancy with 5 mg/kg 4-aminopyrozolopyramidine (4APP), a blocker of hepatic lipoprotein secretion, or with 5 mg/kg 4APP and 1 or 2 mg ovine PRL or 0.1 ml 0.5% phosphoric acid (4APP vehicle). The administration of 4APP reduced serum cholesterol and progesterone levels on days 2-6 of pregnancy and ovarian progesterone on day 6. The reduced progesterone secretion had no effect on embryo implantation. PRL, in the doses used, was incapable of abrogating the effects of 4APP on circulating or ovarian progesterone levels. Ovaries and adrenals, but not kidneys, of pseudopregnant rats exhibited specific and saturable uptake of porcine high density lipoprotein (HDL). Time-course studies indicated that the uptake of HDL was rapid in ovaries compared to that in adrenals. Ovaries from rats not only exhibited uptake of porcine HDL, but also were capable of using it for progesterone synthesis. Treatment with 4APP increased the adrenal uptake of HDL, but ovarian uptake was not different from that in the control group. Hypophysectomy reduced both adrenal and ovarian uptake of HDL. In adrenals only ACTH at the dose employed ameliorated reduction of HDL uptake induced by hypophysectomy, while in the ovaries, both PRL and LH reversed the effect of hypophysectomy. The effect of PRL on uptake was specific to (/sup 125/I)HDL and did not alter (/sup 125/I)albumin uptake. It is concluded that: 1) hypophysectomy reduces HDL uptake in the luteinized rat ovary; and 2) PRL and LH replacement therapy maintain ovarian uptake of HDL, suggesting a direct effect of these luteotropins on lipoprotein uptake.

  2. Disruption of the hypothalamic-pituitary-thyroid axis in zebrafish embryo-larvae following waterborne exposure to BDE-47, TBBPA and BPA

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Winson K. [Biochemistry Program, School of Life Sciences, Chinese University of Hong Kong, Sha Tin, Hong Kong (Hong Kong); Chan, King Ming, E-mail: kingchan@cuhk.edu.hk [Biochemistry Program, School of Life Sciences, Chinese University of Hong Kong, Sha Tin, Hong Kong (Hong Kong); Environmental Science Program, School of Life Sciences, Chinese University of Hong Kong, Sha Tin, Hong Kong (Hong Kong)

    2012-02-15

    We performed waterborne exposures of 2,2 Prime ,4,4 Prime -tetrabromodiphenyl ether (BDE-47), tetrabromobisphenol A (TBBPA) or bisphenol A (BPA) on zebrafish (Danio rerio) embryo-larvae and quantitatively measured the expression of genes belonging to the hypothalamic-pituitary-thyroid (HPT) axis to assess for adverse thyroid function. For analysis on the effects of BDE-47, TBBPA and BPA on the hypothalamic-pituitary-thyroid genes, zebrafish embryo-larvae were acutely exposed to lethal concentrations of the chemical agents in order to determine the 96 h-LC50 (96 h lethal median concentration) and 96 h-EC50 (96 h effective median concentration) values. Further exposures at sub-lethal concentrations were then carried out and total RNA samples were extracted to quantify the mRNA expression levels of the genes of interest. In larvae, BDE-47 was found to have significantly induced many genes of interest, namely thyroglobulin, thyroid peroxidase, thyroid receptors {alpha} and {beta}, thyroid stimulating hormone, and transthyretin. TBBPA only significantly induced three genes of interest (thyroid receptor {alpha}, thyroid stimulating hormone, and transthyretin) while BPA only induced thyroid stimulating hormone. In embryos, BDE-47 significantly induced the sodium iodide symporter and thyroid stimulating hormone. TBBPA significantly induced thyroid receptor {alpha} and thyroid stimulating hormone, while BPA did not significantly induce any of the genes. Most genes were only induced at the 75% 96 h-LC50 or 96 h-EC50 value; however, thyroid peroxidase and thyroid stimulating hormone demonstrated upregulation in a level as little as the 10% 96 h-LC50 value. The present study provides a new set of data on zebrafish mRNA induction of hypothalamic-pituitary-thyroid genes from exposure to BDE-47, TBBPA, or BPA. This information would serve useful for elucidating the toxicological mechanism of brominated flame retardants, assessing appropriate safety levels in the environment for

  3. 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.

  4. Processing of pro-opiomelanocortin-derived amidated joining peptide and glycine-extended precursor in monkey pituitary

    DEFF Research Database (Denmark)

    Fenger, M

    1991-01-01

    The molecular forms of proopiomelanocortin (POMC) derived amidated and C-terminal glycine-extended joining peptide from monkey (Macaca mulatta) pituitary were determined. The predominant forms of joining peptide found were the low molecular peptides POMC(76-105) and POMC(76-106), respectively...... sequence of monkey and human POMC extremely conserved, but also the processing patterns are similar. The monkey therefore serves as a suitable model for studying regulation of the processing of POMC and the hypothalamus-pituitary-adrenal axis in man....

  5. Extra-adrenal glucocorticoid synthesis: immune regulation and aspects on local organ homeostasis.

    Science.gov (United States)

    Talabér, Gergely; Jondal, Mikael; Okret, Sam

    2013-11-05

    Systemic glucocorticoids (GCs) mainly originate from de novo synthesis in the adrenal cortex under the control of the hypothalamus-pituitary-adrenal (HPA)-axis. However, research during the last 1-2 decades has revealed that additional organs express the necessary enzymes and have the capacity for de novo synthesis of biologically active GCs. This includes the thymus, intestine, skin and the brain. Recent research has also revealed that locally synthesized GCs most likely act in a paracrine or autocrine manner and have significant physiological roles in local homeostasis, cell development and immune cell activation. In this review, we summarize the nature, regulation and known physiological roles of extra-adrenal GC synthesis. We specifically focus on the thymus in which GC production (by both developing thymocytes and epithelial cells) has a role in the maintenance of proper immunological function.

  6. Pituitary apoplexy presenting with anorexia and hyponatraemia.

    Science.gov (United States)

    Sasaki, Yosuke; Nakata, Kenji; Suzuki, Kenichi; Ando, Yasuyo

    2015-04-09

    Pituitary apoplexy, a syndrome caused by haemorrhage into the pituitary gland, typically manifests as sudden severe headache, visual symptoms and hypopituitarism, including adrenal insufficiency. We report a case of a 65-year-old man with adrenal insufficiency due to pituitary apoplexy presenting with anorexia following temporal headache and diagnosed through evaluation for hyponatraemia. MRI focusing on the pituitary gland helped to confirm the diagnosis. Our experience serves as a useful reminder of this atypical presentation of pituitary apoplexy, also known as 'subclinical pituitary apoplexy,' and underscores the importance of careful evaluation for hyponatraemia using serial urine osmolality, which is useful to distinguish hypovolaemic hyponatraemia from euvolaemic hyponatraemia. Clinicians should consider pituitary apoplexy as a differential diagnosis in cases of anorexia, loss of energy or hyponatraemia, following headache even when the patient is lacking classical symptoms such as severe headache or visual symptoms.

  7. Effects of tyrosine kinase inhibitors on spermatogenesis and pituitary gonadal axis in males with chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Yassin MA

    2014-08-01

    Full Text Available Objective: The introduction of several classes of targeted therapeutics for the treatment of chronic myelogenous leukemia (CML raises the question of whether male fertility is affected and the degree of this affection, if any, among the different generations of tyrosine kinase inhibitors (TKIs. Additionally, when two drugs are equally effective, the drug with less toxic effect on fertility is favourable. Our aims were to evaluate semen parameters and pituitary gonadal function before and four months after starting TKIs namely, dasatinib, nilotinib, and imatinib in patients with CML. Design: Prospective study. Setting, patients and interventions: We studied the effect of TKIs' first generation (imatinib and second generation (dasatinib and nilotinib on semen parameters and endocrine functions in 20 eugonadal male patients with CML, aged between 35 to 51 years. They were receiving imatinib (400 mg once daily, dasatinib (100 mg once daily or nilotinib (300 mg twice daily as upfront therapy. We assessed the serum gonadotropins (LH and FSH and testosterone (T secretion and sperm parameters before and after four months of using these TKIs. Results: Four months after starting TKIs, serum testosterone, LH and FSH concentrations decreased significantly. The total sperm count (SC, total and rapid progressive sperm motility, and % sperms with normal morphology decreased significantly versus pre-treatment. After 4 months of therapy, dasatinib had comparatively the least deleterious effects on SC, ejaculate volume (SV, sperm motility and % of sperms with normal morphology (%NM compared to imatinib and nilotinib. Significant correlations were found between serum T concentrations and semen parameters before and after TKIs therapy including SC (r = 0.658 and r = 0.73 respectively, p < 0.001, rapid progressive motility (r = 0.675 and r = 0.758, respectively; p < 0.001, and the % NM (r = 0.752 and r = 0.834, respectively; p < 0.001. After TKIs therapy, LH were

  8. The Effect of Ecstasy (MDMA on the Number of Ovary Follicles and Hormonal Axis of Pituitary-Gonadal in Immature Rats

    Directory of Open Access Journals (Sweden)

    Zahra Allaeian

    2013-03-01

    Full Text Available Background & Objective: The widespread use of the pills of ecstasy has opened the floodgates to social damage. Severe kidney and liver damage as well amnesia and imbalance are some of ecstasy pills complications. This study evaluated the effect of these pills on the ovary and hormonal axis of pituitary-gonadal axis in rats.   Materials & Methods: Thirty-five female immature Wistar rats were divided into 5 groups of 7 rats, comprising control, sham, experimental 1, experimental 2, and experimental 3 groups. The control group did not receive any solvent or medication; the sham group received physiologic serum (0.2 cc once daily for 14 days; and the experimental groups of 1, 2, and 3 received a solution (0.2 cc once daily containing 0.5, 1, and 2 mg of medication for 14 days via intraperitoneal injection. Hormone measurement was done with the ELISA method. Ovaries were excised to prepare tissue sections and to investigate the number of ovarian follicles. The number of follicles was calculated via the physical dissector technique.   Results: There was a statistically significant difference in body and ovary weight between the control group and the experimental group 3. Also, the number of primary and Graafian follicles decreased significantly. The results did not show a statistically significant difference between the three experimental groups and the control group in terms of FSH and LH hormones, but the rate of progesterone hormone had a meaningful increase.   Conclusion: Use of ecstasy pills exerted a destructive impact on the ovary and progesterone hormone.

  9. A patient-specific model of the negative-feedback control of the hypothalamus-pituitary-thyroid (HPT) axis in autoimmune (Hashimoto's) thyroiditis.

    Science.gov (United States)

    Pandiyan, Balamurugan; Merrill, Stephen J; Benvenga, Salvatore

    2014-09-01

    The purpose of modelling the negative-feedback control mechanism of the hypothalamus-pituitary-thyroid (HPT) axis in autoimmune (Hashimoto's) thyroiditis is to describe the clinical course of euthyroidism, subclinical hypothyroidism and overt hypothyroidism for patients. Thyroid hormone thyroxine (T4) and triiodothyronine (T3) levels are controlled by negative-feedback control through thyroid-stimulating hormone (TSH). T4, like other hormones, can be bound or unbound; the unbound T4 (FT4) is used as a marker for hypothyroidism. Autoimmune thyroiditis is a disease in which the thyroid-infiltrating lymphocytes attack autoantigens in follicle cells, destroying them over a long time. To describe the operation of the feedback control, we developed a mathematical model involving four clinical variables: TSH, FT4, anti-thyroid peroxidase antibodies and the thyroid gland's functional size. The first three variables are regularly measured while the last variable is determined through relationships between the other three variables. The problem of two different time scales for circulating hormones and thyroid damage is addressed using singular perturbation theory. Analysis of the mathematical model establishes stability and conditions under which the diseased state can maintain the slow movement toward diseased state equilibrium. Although we have used four variables in modelling the feedback control through the HPT axis, the predicted clinical course given any set of parameters is shown to depend on the steady-state levels of TSH and FT4. This observation makes possible the development of the clinical charts based only on the levels of TSH, time and potential steady-state values. To validate the model predictions, a dataset obtained from a Sicilian adult population has been employed. © The Authors 2013. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  10. Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis.

    Science.gov (United States)

    Abd El-Twab, Sanaa M; Mohamed, Hanaa M; Mahmoud, Ayman M

    2016-06-01

    Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.

  11. Computational model of the fathead minnow hypothalamic-pituitary-gonadal axis: Incorporating protein synthesis in improving predictability of responses to endocrine active chemicals.

    Science.gov (United States)

    Breen, Miyuki; Villeneuve, Daniel L; Ankley, Gerald T; Bencic, David; Breen, Michael S; Watanabe, Karen H; Lloyd, Alun L; Conolly, Rory B

    2016-01-01

    There is international concern about chemicals that alter endocrine system function in humans and/or wildlife and subsequently cause adverse effects. We previously developed a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows exposed to a model aromatase inhibitor, fadrozole (FAD), to predict dose-response and time-course behaviors for apical reproductive endpoints. Initial efforts to develop a computational model describing adaptive responses to endocrine stress providing good fits to empirical plasma 17β-estradiol (E2) data in exposed fish were only partially successful, which suggests that additional regulatory biology processes need to be considered. In this study, we addressed short-comings of the previous model by incorporating additional details concerning CYP19A (aromatase) protein synthesis. Predictions based on the revised model were evaluated using plasma E2 concentrations and ovarian cytochrome P450 (CYP) 19A aromatase mRNA data from two fathead minnow time-course experiments with FAD, as well as from a third 4-day study. The extended model provides better fits to measured E2 time-course concentrations, and the model accurately predicts CYP19A mRNA fold changes and plasma E2 dose-response from the 4-d concentration-response study. This study suggests that aromatase protein synthesis is an important process in the biological system to model the effects of FAD exposure.

  12. Psychological and endocrine abnormalities in refugees from East Germany: Part I. Prolonged stress, psychopathology, and hypothalamic-pituitary-thyroid axis activity.

    Science.gov (United States)

    Bauer, M; Priebe, S; Kürten, I; Gräf, K J; Baumgartner, A

    1994-01-01

    The influence of prolonged psychological stress on hormonal secretion was investigated in 84 East Germany refugees suffering from psychiatric disorders within 6 weeks of their arrival in West Berlin shortly before or after the fall of the Berlin Wall. Before leaving the German Democratic Republic, these patients had already experienced prolonged stress, which continued after migration. In most cases, the diagnosis was anxious-depressive syndrome with vegetative complaints and symptoms of increased arousal. Their formal DSM-III-R diagnoses (American Psychiatric Association, 1987) included adjustment disorders, depressive disorders, and anxiety disorders (the latter including posttraumatic stress disorder). Serum levels of thyroid stimulating hormone (TSH) and thyroid hormones (thyroxine, free thyroxine, triiodothyronine, and reverse triiodothyronine) were measured and compared with those of 20 healthy control subjects. TSH and all thyroid hormone concentrations were significantly reduced in the patient group. Fifty-two of the patients (62%) were in the hypothyroid range but did not show any clinical signs of hypothyroidism. These disturbances in hormonal secretion were not correlated to any psychiatric diagnosis or to the severity of acute or chronic stress. The marked abnormalities in the hypothalamic-pituitary-thyroid axis seen in these refugees differ from those reported in depression and would seem to reflect severe chronic stress rather than specific psychiatric disorders. The underlying neurochemical mechanisms remain to be investigated.

  13. What Happens After Treatment for Pituitary Tumors?

    Science.gov (United States)

    ... develop pituitary hormone deficiencies after surgery or radiation therapy. These people will need hormone replacement. Thyroid hormone and adrenal steroids can be taken as pills. In men, testosterone can be given to restore sex drive and ...

  14. Management of incidental pituitary tumors

    Directory of Open Access Journals (Sweden)

    Nicholas F. Marko

    2011-11-01

    Full Text Available Pituitary incidentalomas are common lesions for which neurosurgical referrals may become progressively more frequent, given the increasing application of neuroimaging. The initial evaluation of a patient with radiographic evidence of an incidentaloma should focus on addressing two questions: (1 is the lesion causing neurological symptoms, and (2 is the lesion hormonally active? The answers to these two questions provide a framework for subsequent clinical management. The initial patient assessment should include a detailed history and physical examination, including the bedside assessment of visual fields. High-quality MRI imaging is essential, and formal visual field testing should be obtained in patients where the lesion abuts or compresses the optic apparatus. The initial biochemical workup is intended to assess potential pituitary hypo- or hyperfunction and should include measurement of serum levels of prolactin, insulin-like growth factor type-1, free thyroxine, testosterone, and an assessment of axis hypothalamic–pituitary–adrenal axis function. Additional testing may include serum thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone levels. Neurologically-asymptomatic patients without endocrine dysfunction can be managed with observation at regular intervals, including MRI imaging at 6 months and 1 year and then annually for a period of 3 years. Follow-up biochemical assessment is not necessary in the absence of clinical symptoms or radiographic enlargement of the lesion. After 3 years the follow-up interval may be prolonged, although closer follow-up may be indicated for patients with lesions C1 cm. Most patients who either present with or who subsequently develop neurologic or endocrinologic symptoms should be considered for surgery as the first-line therapy.

  15. Childhood stressful events, HPA axis and anxiety disorders.

    Science.gov (United States)

    Faravelli, Carlo; Lo Sauro, Carolina; Godini, Lucia; Lelli, Lorenzo; Benni, Laura; Pietrini, Francesco; Lazzeretti, Lisa; Talamba, Gabriela Alina; Fioravanti, Giulia; Ricca, Valdo

    2012-02-22

    Anxiety disorders are among the most common of all mental disorders and their pathogenesis is a major topic in psychiatry, both for prevention and treatment. Early stressful life events and alterations of hypothalamic pituitary adrenal (HPA) axis function seem to have a significant role in the onset of anxiety. Existing data appear to support the mediating effect of the HPA axis between childhood traumata and posttraumatic stress disorder. Findings on the HPA axis activity at baseline and after stimuli in panic disordered patients are inconclusive, even if stressful life events may have a triggering function in the development of this disorder. Data on the relationship between stress, HPA axis functioning and obsessive-compulsive disorder (OCD) are scarce and discordant, but an increased activity of the HPA axis is reported in OCD patients. Moreover, normal basal cortisol levels and hyper-responsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally, abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. While several hypothesis have attempted to explain these findings over time, currently the most widely accepted theory is that early stressful life events may provoke alterations of the stress response and thus of the HPA axis, that can endure during adulthood, predisposing individuals to develop psychopathology. All theories are reviewed and the authors conclude that childhood life events and HPA abnormalities may be specifically and transnosographically related to all anxiety disorders, as well as, more broadly, to all psychiatric disorders.

  16. Expression of chemokine CXCL12 and its receptor CXCR4 in folliculostellate (FS) cells of the rat anterior pituitary gland: the CXCL12/CXCR4 axis induces interconnection of FS cells.

    Science.gov (United States)

    Horiguchi, Kotaro; Ilmiawati, Cimi; Fujiwara, Ken; Tsukada, Takehiro; Kikuchi, Motoshi; Yashiro, Takashi

    2012-04-01

    The anterior pituitary gland is composed of five types of hormone-producing cells plus folliculostellate (FS) cells, which do not produce classical anterior pituitary hormones. FS cells are interconnected by cytoplasmic processes and encircle hormone-producing cells or aggregate homophilically. Using living-cell imaging of primary culture, we recently reported that some FS cells precisely extend their cytoplasmic processes toward other FS cells and form interconnections with them. These phenomena suggest the presence of a chemoattractant factor that facilitates the interconnection. In this study, we attempted to discover the factor that induces interconnection of FS cells and succeeded in identifying chemokine (CXC)-L12 and its receptor CXCR4 as potential candidate molecules. CXCL12 is a chemokine of the CXC subfamily. It exerts its effects via CXCR4, a G protein-coupled receptor. The CXCL12/CXCR4 axis is a potent chemoattractant for many types of neural cells. First, we revealed that CXCL12 and CXCR4 are expressed by FS cells in rat anterior pituitary gland. Next, to clarify the function of the CXCL12/CXCR4 axis in FS cells, we observed living anterior pituitary cells in primary culture with specific CXCL12 inhibitor or CXCR4 antagonist and noted that extension of cytoplasmic processes and interconnection of FS cells were inhibited. Finally, we examined FS cell migration and invasion by using Matrigel matrix assays. CXCL12 treatment resulted in markedly increased FS cell migration and invasion. These data suggest that FS cells express chemokine CXCL12 and its receptor CXCR4 and that the CXCL12/CXCR4 axis evokes interconnection of FS cells.

  17. A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas exposed to 17α-ethynylestradiol and 17β-trenbolone

    Directory of Open Access Journals (Sweden)

    Lazorchak James M

    2011-05-01

    Full Text Available Abstract Background Endocrine disrupting chemicals (e.g., estrogens, androgens and their mimics are known to affect reproduction in fish. 17α-ethynylestradiol is a synthetic estrogen used in birth control pills. 17β-trenbolone is a relatively stable metabolite of trenbolone acetate, a synthetic androgen used as a growth promoter in livestock. Both 17α-ethynylestradiol and 17β-trenbolone have been found in the aquatic environment and affect fish reproduction. In this study, we developed a physiologically-based computational model for female fathead minnows (FHM, Pimephales promelas, a small fish species used in ecotoxicology, to simulate how estrogens (i.e., 17α-ethynylestradiol or androgens (i.e., 17β-trenbolone affect reproductive endpoints such as plasma concentrations of steroid hormones (e.g., 17β-estradiol and testosterone and vitellogenin (a precursor to egg yolk proteins. Results Using Markov Chain Monte Carlo simulations, the model was calibrated with data from unexposed, 17α-ethynylestradiol-exposed, and 17β-trenbolone-exposed FHMs. Four Markov chains were simulated, and the chains for each calibrated model parameter (26 in total converged within 20,000 iterations. With the converged parameter values, we evaluated the model's predictive ability by simulating a variety of independent experimental data. The model predictions agreed with the experimental data well. Conclusions The physiologically-based computational model represents the hypothalamic-pituitary-gonadal axis in adult female FHM robustly. The model is useful to estimate how estrogens (e.g., 17α-ethynylestradiol or androgens (e.g., 17β-trenbolone affect plasma concentrations of 17β-estradiol, testosterone and vitellogenin, which are important determinants of fecundity in fish.

  18. [Forensic medical estimation of the morphological changes in the myocardium and hypothalamo-pituitary-adrenal system in case of sudden cardiac death].

    Science.gov (United States)

    Pigolkin, Iu I; Dolzhanskiĭ, O V; Gromova, T M

    2012-01-01

    This morphological, morphometric, and immunohistochemical study of the myocardium, adrenal gland, and hypothalamus included 50 corpses of men aged from 25-49 years deceased by reason of acute coronary failure associated with coronary heart disease. The commonest lesions in the myocardium were contractures (54.3 +/- 3.5% [51.2; 57.8%]), cyclic deformation (44.7 +/- 6.3% [38.2; 51.4%]), and dissociation of cardiomyocytes (61.2 +/- 2.3% [56.3; 64.8%]). The sinoatrial and atrioventricular nodes of the heart contained large amounts of adrenaline-positive cells (45.6 +/- 4.5% [40.1; 48.7%]) and 34.2 +/- 2.9% [31.2; 37.4%]). The equally large numbers of adrenaline-positive cells were detected in the adrenal medulla (67.2 +/- 6.8% [61.9; 74.3%]). The arcuate, supraoptic, and paraventricular nuclei of the hypothalamus underwent reversible changes of neutron content (the degree of damage 25.6 +/- 4.8% [21.2; 29.8%]) and contained large amounts of noradrenaline-positive and dopamine-positive neural cells (54.2 +/- 3.6% [51.4; 59.3%]) and 28.7 +/- 2.1% [23.4; 31.7%]) respectively. It is concluded that the morphometric and immunohistochemical changes detected in the present study can be used as the additional forensic medical criteria for diagnostics of death from acute coronary failure associated with coronary heart disease.

  19. Embryo number and periconceptional undernutrition in the sheep have differential effects on adrenal epigenotype, growth, and development.

    Science.gov (United States)

    Williams-Wyss, Olivia; Zhang, Song; MacLaughlin, Severence M; Kleemann, David; Walker, Simon K; Suter, Catherine M; Cropley, Jennifer E; Morrison, Janna L; Roberts, Claire T; McMillen, I Caroline

    2014-07-15

    Exposure to poor maternal nutrition around the time of conception results in an early prepartum activation of the fetal pituitary-adrenal axis and in increased adrenal growth and stress response after birth associated with epigenetic changes in a differentially methylated region (DMR) of adrenal IGF2/H19. We have determined the effects of maternal undernutrition during the periconceptional period (PCUN: 70% of control intake from 60 days before until 6 days after conception) and early preimplantation period (PIUN: 70% of control intake for 6 days after conception) on fetal plasma ACTH and cortisol concentrations and fetal adrenal ACTHR, StAR, 3βHSD, CYP11B, CYP17, TGFβ1, IGF1, IGF1R, IGF2, and IGF2R mRNA expression and the methylation level of sites within the DMRs of IGF2/H19 and IGF2R in the adrenal of twin and singleton fetuses at 136-138 days gestation. Being a twin resulted in a delayed prepartum increase in fetal ACTH and in a lower cortisol response to CRH in the control but not PCUN and PIUN groups. PCUN, but not PIUN, resulted in an increase in adrenal weight and CYP17 expression in singletons, a decrease in adrenal IGF2 expression in singletons, and an increase in adrenal IGF2R expression in both twins and singletons. IGF2/H19 and IGF2R DMR methylation levels and ACTHR expression were lower in the twin adrenal. Thus, exposure of the oocyte and embryo to maternal undernutrition or to the environment of a twin pregnancy have differential effects on epigenetic and other factors that regulate fetal adrenal growth and IGF2 and IGF2R expression.

  20. No pituitary gland volume change in medication-free depressed patients.

    Science.gov (United States)

    Eker, Cagdas; Ovali, Gulgun Yilmaz; Ozan, Erol; Eker, Ozlem Donat; Kitis, Omer; Coburn, Kerry; Gonul, Ali Saffet

    2008-10-01

    Increased serum cortisol levels and a hyperactive hypothalamo-pituitary-adrenal (HPA) axis have been proposed to play an important role in the pathophysiology of Major Depressive Disorder (MDD). However, there are inconsistent results regarding pituitary gland volume (PGV), which is one of the key elements of the HPA axis evaluated by MRI in depressed patients. In this study, we analyzed the PGV of medication-free moderately depressed MDD patients (N=34) and age and sex matched healthy controls (N=39). PGV did not differ between MDD patients and healthy controls [mean volume+/-S.D.; 0.76+/-0.17 cm3 and 0.75+/-0.14 cm3; ANCOVA, F1,69=1.25 p>0.05; respectively]. Our results confirm that volumetric PGV changes are not crucial for depression pathophysiology among unmedicated, moderately depressed adults.

  1. Gut Microbiota-brain Axis

    Institute of Scientific and Technical Information of China (English)

    Hong-Xing Wang; Yu-Ping Wang

    2016-01-01

    Objective:To systematically review the updated information about the gut microbiota-brain axis.Data Sources:All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of"gut microbiota","gut-brain axis",and "neuroscience".Study Selection:All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results:It is well-recognized that gut microbiota affects the brain's physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain's neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions:Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.

  2. Adrenal enlargement and failure of suppression of circulating cortisol by dexamethasone in patients with malignancy.

    Science.gov (United States)

    Jenkins, P J; Sohaib, S A; Trainer, P J; Lister, T A; Besser, G M; Reznek, R

    1999-08-01

    The aim of this study was to further elucidate the activity of the hypothalamo-pituitary-adrenal (HPA) axis in patients with malignancy and to correlate this with the size of the adrenal glands. Fourteen patients with a variety of malignancies were studied prior to receiving cytotoxic chemotherapy. During routine staging computerized tomographic (CT) scans, the size of the body, medial and lateral limbs of the adrenal glands were measured and compared with those of a normal group of patients studied previously. Measurements of 09:00 h serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were made before and after the administration of dexamethasone (0.5 mg 6-hourly for 48 h) in addition to the peak cortisol response to i.v corticotropin releasing hormone (CRH). Overall, patients with malignancy had significantly larger adrenal glands than patients without malignancy; those with non-haematological malignancies had larger glands than patients with haematological malignancies. Following dexamethasone to suppress circulating cortisol levels, nine patients (64%) demonstrated abnormal resistance with cortisol levels > 50 nmol l(-1): mean value 294 nmol l(-1) (range 67-1147). Those patients who failed to suppress after dexamethasone had significantly larger adrenal glands than those that did suppress and tended to have non-haematological malignancies. ACTH levels were undetectable or low in three patients in whom it was measured and who did not suppress with dexamethasone. Following CRH, the cortisol levels were highest (823 and 853 nmol l(-1)) in two of these patients. Malignancy is associated with diffuse enlargement of the adrenal glands and resistance to dexamethasone-induced suppression of the HPA axis, which is not due to ectopic ACTH secretion. This disturbance of the normal control of the HPA