Inactivation of the DMH selectively inhibits the ACTH and corticosterone responses to hypoglycemia

2004 ◽  
Vol 286 (1) ◽  
pp. R123-R128 ◽  
Author(s):  
Scott B. Evans ◽  
Charles W. Wilkinson ◽  
Pam Gronbeck ◽  
Jennifer L. Bennett ◽  
Aryana Zavosh ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Control Level ◽  
Specific Role ◽  
Hypothalamic Pituitary Adrenal ◽  
Single Bout ◽  
Corticosterone Response

We have previously reported that repeated bouts of insulin-induced hypoglycemia (IIH) in the rat result in blunted activation of the paraventricular, arcuate, and dorsomedial hypothalamic (DMH) nuclei. Because DMH activation has been implicated in the sympathoadrenal and hypothalamic-pituitary-adrenal (HPA) responses to stressors, we hypothesized that its blunted activation may play a role in the impaired counterregulatory response that is also observed with repeated bouts of IIH. In the present study, we evaluated the role of normal DMH activation in the counterregulatory response to a single bout of IIH. Local infusion of lidocaine ( n = 8) to inactivate the DMH during a 2-h bout of IIH resulted in a significant overall decrease of the ACTH response and a delay of onset of the corticosterone response compared with vehicle-infused controls ( n = 9). We observed suppression of the ACTH response at time ( t) = 90 and 120 min (50 ± 12 and 63 ± 6%, respectively, of control levels) and early suppression of the corticosterone response at t = 30 min (59 ± 13% of the control level). The epinephrine, norepinephrine, and glucagon responses were not altered by DMH inactivation. Our finding suggests that DMH inactivation may play a specific role in decreasing the HPA axis response after repeated bouts of IIH.

scholarly journals Genes and hormones of the hypothalamic–pituitary–adrenal axis in post-traumatic stress disorder. What is their role in symptom expression and treatment response?

2021 ◽  
Author(s):  
Susanne Fischer ◽  
Tabea Schumacher ◽  
Christine Knaevelsrud ◽  
Ulrike Ehlert ◽  
Sarah Schumacher
Keyword(s):  
Hpa Axis ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Ptsd Symptoms ◽  
Post Traumatic Stress ◽  
Alternative Treatments ◽  
Hypothalamic Pituitary Adrenal ◽  
Post Traumatic

Abstract Background Less than half of all individuals with post-traumatic stress disorder (PTSD) remit spontaneously and a large proportion of those seeking treatment do not respond sufficiently. This suggests that there may be subgroups of individuals who are in need of augmentative or alternative treatments. One of the most frequent pathophysiological findings in PTSD is alterations in the hypothalamic–pituitary–adrenal (HPA) axis, including enhanced negative feedback sensitivity and attenuated peripheral cortisol. Given the role of the HPA axis in cognition, this pattern may contribute to PTSD symptoms and interfere with key processes of standard first-line treatments, such as trauma-focused cognitive behavioural therapy (TF-CBT). Methods This review provides a comprehensive summary of the current state of research regarding the role of HPA axis functioning in PTSD symptoms and treatment. Results Overall, there is preliminary evidence that hypocortisolaemia contributes to symptom manifestation in PTSD; that it predicts non-responses to TF-CBT; and that it is subject to change in parallel with positive treatment trajectories. Moreover, there is evidence that genetic and epigenetic alterations within the genes NR3C1 and FKBP5 are associated with this hypocortisolaemic pattern and that some of these alterations change as symptoms improve over the course of treatment. Conclusions Future research priorities include investigations into the role of the HPA axis in day-to-day symptom variation, the time scale in which biological changes in response to treatment occur, and the effects of sex. Furthermore, before conceiving augmentative or alternative treatments that target the described mechanisms, multilevel studies are warranted.

Headliner in Physiology and Management of Childhood Asthma: Hypothalamic-Pituitary-Adrenal Axis

2020 ◽  
Vol 16 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Nese Akcan ◽  
Nerin N. Bahceciler
Keyword(s):  
Side Effects ◽  
Hpa Axis ◽  
Inhaled Corticosteroids ◽  
Cushing Syndrome ◽  
Early Recognition ◽  
Persistent Asthma ◽  
Receptor Expression ◽  
Hypothalamic Pituitary Adrenal

Asthma is the most common chronic inflammatory disease of children. Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy which are the most effective, commonly used treatment of persistent asthma. Mostly, studies on the relationship between asthma and cortisol have focused on side effects of treatment. Recently, asthmatic patients not treated with ICS have been reported to have an attenuated activity and/or responsiveness of their Hypothalamic-Pituitary- Adrenal (HPA) axis. Moreover, it has been proposed that asthma worsening with stress may be due to a dysfunctional HPA axis, or cortisol insensitivity due to chronic psychological stress through impaired glucocorticoid receptor expression or function. Although long-term ICS treatment might produce adrenal suppression or iatrogenic Cushing syndrome, improvement of adrenal function has also been detected in some of asthmatic cases. Thus, the response scheme of HPA axis still contains undiscovered features in asthma. The management of asthma can be improved by increasing knowledge on the role of HPA axis in asthma pathophysiology. The risk for side effects of ICS can be minimized through increased awareness, early recognition of at-risk patients and regular patient follow-up. This review was written to draw attention to the role of HPA axis in both asthma and its treatment and to illustrate a follow up algorithm of HPA axis in the management of asthma.

scholarly journals Hypothalamic-Pituitary-Adrenal Axis Activity of Newborn Mice Rapidly Desensitizes to Repeated Maternal Absence but Becomes Highly Responsive to Novelty

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6366-6377 ◽  
Author(s):  
L. Enthoven ◽  
M. S. Oitzl ◽  
N. Koning ◽  
M. van der Mark ◽  
E. R. de Kloet
Keyword(s):  
Glucocorticoid Receptor ◽  
Receptor Antagonist ◽  
Hpa Axis ◽  
Mineralocorticoid Receptor ◽  
Maternal Separation ◽  
Mineralocorticoid Receptor Antagonist ◽  
Newborn Mice ◽  
Hypothalamic Pituitary Adrenal ◽  
The Third ◽  
Corticosterone Response

In CD1 mice we investigated the hypothalamic-pituitary-adrenal (HPA) axis response to maternal separation for 8 h daily from postnatal d 3 to 5. At d 3 a slow separation-induced corticosterone response developed that peaked after 8 h, and the pups became responsive to stressors. On the second and third day, the response to 8 h separation rapidly attenuated, whereas the response to novelty did not, a pattern reflected by the hypothalamic c-fos mRNA response. If maternal separation and exposure to novelty were combined, then after the third such daily exposure, the sensitivity to the stressor was further enhanced. Meanwhile, basal corticosterone and ACTH levels were persistently suppressed 16 h after pups were reunited with their mothers. To explain the HPA axis desensitization after repeated separation, we found that circulating ghrelin levels increased and glucose levels decreased after all periods of maternal separation, ruling out a role of altered metabolism. Glucocorticoid feedback was not involved either because a glucocorticoid receptor antagonist amplified the corticosterone response after the first but became ineffective after the third separation. In contrast, a mineralocorticoid receptor antagonist decreased and increased corticosterone levels after the first and third period of separation, respectively. In conclusion, the newborn’s HPA axis readily desensitizes to repeated daily maternal separation, but continues to respond to novelty in a manner influenced by a central mineralocorticoid receptor- rather than glucocorticoid receptor-mediated mechanism.

scholarly journals Vitamin A regulates hypothalamic–pituitary–adrenal axis status in LOU/C rats

2013 ◽  
Vol 219 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Nathalie Marissal-Arvy ◽  
Rachel Hamiani ◽  
Emmanuel Richard ◽  
Marie-Pierre Moisan ◽  
Véronique Pallet
Keyword(s):  
Vitamin A ◽  
Hpa Axis ◽  
Restraint Stress ◽  
Vitamin A Deficiency ◽  
Plasma Corticosterone ◽  
Hypothalamic Pituitary Adrenal ◽  
Corticosteroid Receptors ◽  
Vitamin A Status ◽  
Corticosterone Response ◽  
Hpa Axis Activity

The aim of this study was to explore the involvement of retinoids in the hypoactivity and hyporeactivity to stress of the hypothalamic–pituitary–adrenal (HPA) axis in LOU/C rats. We measured the effects of vitamin A deficiency administered or not with retinoic acid (RA) on plasma corticosterone in standard conditions and in response to restraint stress and on hypothalamic and hippocampal expression of corticosteroid receptors, corticotropin-releasing hormone and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in LOU/C rats. Interestingly, under control conditions, we measured a higher plasma concentration of retinol in LOU/C than in Wistar rats, which could contribute to the lower basal activity of the HPA axis in LOU/C rats. Vitamin A deficiency induced an increased HPA axis activity in LOU/C rats, normalized by RA administration. Compared with LOU/C control rats, vitamin A-deficient rats showed a delayed and heightened corticosterone response to restraint stress. The expression of corticosteroid receptors was strongly decreased by vitamin A deficiency in the hippocampus, which could contribute to a less efficient feedback by corticosterone on HPA axis tone. The expression of 11β-HSD1 was increased by vitamin A deficiency in the hypothalamus (+62.5%) as in the hippocampus (+104.7%), which could lead to a higher production of corticosterone locally and contribute to alteration of the hippocampus. RA supplementation treatment restored corticosterone concentrations and 11β-HSD1 expression to control levels. The high vitamin A status of LOU/C rats could contribute to their low HPA axis activity/reactivity and to a protective effect against 11β-HSD1-mediated deleterious action on cognitive performances during ageing.

Leukemia inhibitory factor regulates glucocorticoid receptor expression in the hypothalamic-pituitary-adrenal axis

2005 ◽  
Vol 289 (5) ◽  
pp. E857-E863 ◽  
Author(s):  
Anastasia Kariagina ◽  
Svetlana Zonis ◽  
Mahta Afkhami ◽  
Dmitry Romanenko ◽  
Vera Chesnokova
Keyword(s):  
Glucocorticoid Receptor ◽  
Hpa Axis ◽  
Leukemia Inhibitory Factor ◽  
Dominant Negative ◽  
Receptor Expression ◽  
Inhibitory Factor ◽  
Mrna Levels ◽  
Hypothalamic Pituitary Adrenal ◽  
Protein Levels

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine belonging to the gp130 family. LIF is induced peripherally and within the brain during inflammatory or chronic autoimmune diseases and is a potent stimulator of the hypothalamic-pituitary-adrenal (HPA) axis. Here we investigated the role of LIF in mediating glucocorticoid receptor (GR) expression in the HPA axis. LIF treatment (3 μg/mouse, ip) markedly decreased GR mRNA levels in murine hypothalamus (5-fold, P < 0.01) and pituitary (1.7-fold, P < 0.01) and downregulated GR protein levels. LIF decreased GR expression in murine corticotroph cell line AtT20 within 2 h, and this effect was sustained for 8 h after treatment. LIF-induced GR mRNA reduction was abrogated in AtT20 cells overexpressing dominant-negative mutants of STAT3, indicating that intact JAK-STAT signaling is required to mediate LIF effects on GR expression. Conversely, mice with LIF deficiency exhibited increased GR mRNA levels in the hypothalamus and pituitary (3.5- and 3.5-fold, respectively; P < 0.01 for both) and increased GR protein expression when compared with wild-type littermates. The suppressive effects of dexamethasone on GR were more pronounced in LIF-null animals. These data suggest that LIF maintains the HPA axis activation by decreasing GR expression and raise the possibility that LIF might contribute to the development of central glucocorticoid resistance during inflammation.

Genetics of the Hypothalamic-pituitary-adrenal (HPA) Axis - a Systemic Stress Modulator in Relation to Suicidal Behaviour

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
D. Wasserman ◽  
M. Sokolowski ◽  
J. Wasserman
Keyword(s):  
Genetic Variation ◽  
Tyrosine Hydroxylase ◽  
Hpa Axis ◽  
Suicidal Behaviour ◽  
Genetic Factors ◽  
Twin Studies ◽  
Adoption Studies ◽  
Hypothalamic Pituitary Adrenal ◽  
Systemic Stress

Suicide, a phenomenon characterised by heterogeneous and complex causes affects about one million people each year.Twin studies, adoption studies and family studies indicate the role of genetic factors in suicidal behaviours. Psychobiological hypotheses regarding suicidal behaviours involve neurotransmitters such as serotonin, norepinephrine, dopamine, and their correlation to psychological functions as well as the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Whereas the genes of e.g. the 5HT system and of the key NA-biosynthesis enzyme, tyrosine hydroxylase, have been studied extensively in this context the genes in the HPA axis have only begun to be investigated.Our novel results on the genetic variation in the CRHR1 gene in connection to depression and stress among suicidal individuals and in the TBX 19 gene, which is regulated by CRH, suggest that genetic variation in the CRH-mediated regulation of the HPA axis is a factor of importance in suicidality, especially in males with depression.

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