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Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease
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Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 August 2017) | Viewed by 156339

Special Issue Editor

Dr. Sharon DeMorrow

E-Mail Website
Guest Editor
Texas A&M Health Science Center, College of Medicine and the Central Texas Veterans Healthcare System, Temple, TX, USA
Interests: cholestatic liver diseases; hypothalamic neuropeptides; hepatic encephalopathy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will include a selection of recent research topics and current review articles related to the role of the hypothalamic–pituitary–adrenal (HPA) axis in health and disease. Up-to-date review articles, commentaries and experimental papers are all welcome.
The HPA axis describes a complex set of positive and negative feedback influences between the hypothalamus, pituitary gland, and adrenal gland. These positive and negative feedback mechanisms work in a neuroendocrine manner in order to modulate a number of physiological processes such as immunity, digestion, and the body’s response to stress.
The mechanism by which the HPA axis remains in homeostasis depends widely on the release and uptake of several key regulatory molecules. The hypothalamus contains neuroendocrine neurons that secrete corticotropin-releasing hormone (CRH). CRH will, in turn, act on the pituitary gland to stimulate the production and release of adrenocorticotropic hormone (ACTH) into the circulation. Circulating ACTH then induces the adrenal gland to synthesize and release corticosteroids, such as cortisol and corticosterone. These circulating corticosteroids modulate the vast array of physiological processes influenced by the HPA axis and are also responsible for initiating a negative feedback loop on the HPA axis via activation of the glucocorticoid receptor (GR) in the brain in order to shut down corticosteroid production. This axis is dysregulated in a number of pathologies.
This Special Issue will bring together a number of manuscripts delineating the various roles that the HPA axis plays in the pathology of different organs throughout the body in relation to a number of disease processes.

Dr. Sharon DeMorrow
Guest Editor

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Keywords

  • HPA axis
  • hypothalamus
  • glucocorticoids
  • CRH
  • organs
  • disease

Published Papers (15 papers)

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Editorial

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5 pages, 170 KiB  
Editorial
Role of the Hypothalamic–Pituitary–Adrenal Axis in Health and Disease
by Sharon DeMorrow
Int. J. Mol. Sci. 2018, 19(4), 986; https://doi.org/10.3390/ijms19040986 - 26 Mar 2018
Cited by 48 | Viewed by 10798
Abstract
The Hypothalamic–Pituitary–adrenal (HPA) axis describes a complex set of positive and negative feedback influences between the hypothalamus, pituitary gland, and adrenal gland.[...] Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)

Research

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8 pages, 235 KiB  
Article
A Pilot Study of Stress System Activation in Children Enrolled in a Targeted Prevention Program: Implications for Personalization
by Bonnie Klimes-Dougan, David A. Klingbeil, Alaa Houri, Kathryn R. Cullen, Meredith Gunlicks-Stoessel and Gerald August
Int. J. Mol. Sci. 2018, 19(2), 361; https://doi.org/10.3390/ijms19020361 - 25 Jan 2018
Cited by 1 | Viewed by 3503
Abstract
Empirically validated interventions addressing childhood psychological problems are now readily available, but success likely depends in part on accurately identifying which children will benefit from which intervention. This pilot study examined the stress activation and response system, first as a way to differentiate [...] Read more.
Empirically validated interventions addressing childhood psychological problems are now readily available, but success likely depends in part on accurately identifying which children will benefit from which intervention. This pilot study examined the stress activation and response system, first as a way to differentiate high versus low-risk children, and second to explore indicators of the stress system associated with favorable intervention response. Method. Participants (N = 43, 58% male) were school-aged children who qualified for inclusion in the Early Risers “Skills for Success” Prevention Program based on their elevated levels of aggressive and/or socially withdrawn behavior and a normally developing comparison group. Compared to the normally developing group, children who were participants in the intervention exhibited a more blunted cortisol response to the stress paradigm. However, for the children in the intervention group, elevated cortisol levels at the start of the stress paradigm were concurrently associated with internalizing problems and predictive of improvement in internalizing problems over time. These findings provide preliminary evidence that hypothalamic pituitary adrenal (HPA) axis biological variables may be helpful tools for identifying children who would benefit from intervention and personalizing interventions. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
15694 KiB  
Article
Glucocorticoids Cause Gender-Dependent Reversal of Hepatic Fibrosis in the MDR2-Knockout Mouse Model
by Anca D. Petrescu, Stephanie Grant, Gabriel Frampton, Jessica Kain, Karam Hadidi, Elaina Williams, Matthew McMillin and Sharon DeMorrow
Int. J. Mol. Sci. 2017, 18(11), 2389; https://doi.org/10.3390/ijms18112389 - 10 Nov 2017
Cited by 13 | Viewed by 6947
Abstract
Hepatic cholestasis is associated with a significant suppression of the hypothalamus-pituitary-adrenal axis (HPA). In the present study, we tested the hypothesis that activation of the HPA axis by corticosterone treatment can reverse liver inflammation and fibrosis in a multidrug resistance protein 2 knockout [...] Read more.
Hepatic cholestasis is associated with a significant suppression of the hypothalamus-pituitary-adrenal axis (HPA). In the present study, we tested the hypothesis that activation of the HPA axis by corticosterone treatment can reverse liver inflammation and fibrosis in a multidrug resistance protein 2 knockout (MDR2KO) transgenic mouse model of hepatic cholestasis. Friend Virus B NIH-Jackson (FVBN) control and MDR2KO male and female mice were treated with vehicle or corticosterone for two weeks, then serum and liver analyses of hepatic cholestasis markers were performed. Indicators of inflammation, such as increased numbers of macrophages, were determined. MDR2KO mice had lower corticotropin releasing hormone and corticosterone levels than FVBN controls in the serum. There was a large accumulation of CD68 and F4/80 macrophages in MDR2KO mice livers, which indicated greater inflammation compared to FVBNs, an effect reversed by corticosterone treatment. Intrahepatic biliary duct mass, collagen deposition and alpha smooth muscle actin (αSMA) were found to be much higher in livers of MDR2KO mice than in controls; corticosterone treatment significantly decreased these fibrosis markers. When looking at the gender-specific response to corticosterone treatment, male MDR2KO mice tended to have a more pronounced reversal of liver fibrosis than females treated with corticosterone. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
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1230 KiB  
Article
Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs
by René Schiffner, Guadalupe L. Rodríguez-González, Florian Rakers, Marius Nistor, Peter W. Nathanielsz, Teodora Daneva, Matthias Schwab, Thomas Lehmann and Martin Schmidt
Int. J. Mol. Sci. 2017, 18(11), 2241; https://doi.org/10.3390/ijms18112241 - 27 Oct 2017
Cited by 12 | Viewed by 4685
Abstract
Background: Prenatal glucocorticoid administration alters the activity of the fetal hypothalamic-pituitary-adrenocortical axis (HPAA), and correspondingly the adenocorticotropic hormone (ACTH) and cortisol levels after birth. The dosages required for these effects are critically discussed. Activation of the HPAA is related to metabolic syndrome and [...] Read more.
Background: Prenatal glucocorticoid administration alters the activity of the fetal hypothalamic-pituitary-adrenocortical axis (HPAA), and correspondingly the adenocorticotropic hormone (ACTH) and cortisol levels after birth. The dosages required for these effects are critically discussed. Activation of the HPAA is related to metabolic syndrome and diabetes mellitus. Hypoglycemia is the classic side effect of antidiabetic treatment. We hypothesized that a low dosage of dexamethasone in late pregnancy alters the HPAA response to hypoglycemia in pigs. Methods: 12 pregnant sows were randomly assigned to two groups which received either a low-dose intramuscular injection (99th and 100th day of gestation) of dexamethasone (0.06 μg/kg body weight) or vehicle. Three months after birth, 18 dexamethasone-treated anaesthetized offspring and 12 control offspring underwent a 75 min hypoglycemic clamp (blood glucose below 4 mmol/L) procedure. Heart rate (HR), blood pressure, ACTH and cortisol levels and body weight (at birth and after three months) were recorded. Results: Dexamethasone-treated animals exhibited significantly elevated ACTH (139.9 ± 12.7 pg/mL) and cortisol (483.1 ± 30.3 nmol/L) levels during hypoglycemia as compared to the control group (41.7 ± 6.5 pg/mL and 257.9 ± 26.7 nmol/L, respectively), as well as an elevated HR (205.5 ± 5.7 bpm) and blood pressure (systolic: 128.6 ± 1.5, diastolic: 85.7 ± 0.7 mmHg) response as compared to the control group (153.2 ± 4.5 bpm; systolic: 118.6 ± 1.6, diastolic: 79.5 ± 1.4 mmHg, respectively; p < 0.001). Conclusions: Low-dose prenatal administration of dexamethasone not only exerts effects on the HPAA (ACTH and cortisol concentration) and vital parameters (HR and diastolic blood pressure) under baseline conditions, but also on ACTH, HR and systolic blood pressure during hypoglycemia. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
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1737 KiB  
Article
Diurnal Hypothalamic-Pituitary-Adrenal Axis Measures and Inflammatory Marker Correlates in Major Depressive Disorder
by Kelly Doolin, Chloe Farrell, Leonardo Tozzi, Andrew Harkin, Thomas Frodl and Veronica O’Keane
Int. J. Mol. Sci. 2017, 18(10), 2226; https://doi.org/10.3390/ijms18102226 - 24 Oct 2017
Cited by 46 | Viewed by 9784
Abstract
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory systems is a consistent finding in patients with Major Depressive Disorder (MDD). Cortisol is often assessed by measurement of the cortisol awakening response (CAR) and/or diurnal cortisol levels. Some methods of cortisol measurement overestimate cortisol [...] Read more.
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory systems is a consistent finding in patients with Major Depressive Disorder (MDD). Cortisol is often assessed by measurement of the cortisol awakening response (CAR) and/or diurnal cortisol levels. Some methods of cortisol measurement overestimate cortisol concentration due to detection of other glucocorticoids including the relatively inert cortisone, therefore this study aimed to assess the presence of both cortisol and cortisone, and the cortisol-cortisone catalyzing enzyme 11β-hydroxysteroiddehydrogenase type 1 (11β-HSD1), in depressed patients and controls. Because the HPA axis is known to regulate the body’s immune system, relationships between measures of cytokines and cortisol were also assessed. Saliva samples were collected from 57 MDD patients and 40 healthy controls at five post-wakening time points (0, +30, +60, +720 and +750 min). Glucocorticoid concentrations were measured by liquid chromatography mass spectrometry. Whole blood mRNA expression of several inflammatory markers was measured by quantitative polymerase chain reaction. This study replicated the common finding of elevated morning cortisol and reduced CAR reactivity in MDD and found no differences in cortisone or 11β-HSD1 mRNA measures. There was a negative association between interleukin 1-β (IL-1β) mRNA and morning cortisol reactivity within the depressed group, indicating that dysregulation of the HPA axis and immune system may be interconnected. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
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1673 KiB  
Article
NPFFR2 Activates the HPA Axis and Induces Anxiogenic Effects in Rodents
by Ya-Tin Lin, Yu-Lian Yu, Wei-Chen Hong, Ting-Shiuan Yeh, Ting-Chun Chen and Jin-Chung Chen
Int. J. Mol. Sci. 2017, 18(8), 1810; https://doi.org/10.3390/ijms18081810 - 21 Aug 2017
Cited by 20 | Viewed by 11258
Abstract
Neuropeptide FF (NPFF) belongs to the RFamide family and is known as a morphine-modulating peptide. NPFF regulates various hypothalamic functions through two receptors, NPFFR1 and NPFFR2. The hypothalamic-pituitary-adrenal (HPA) axis participates in physiological stress response by increasing circulating glucocorticoid levels and modulating emotional [...] Read more.
Neuropeptide FF (NPFF) belongs to the RFamide family and is known as a morphine-modulating peptide. NPFF regulates various hypothalamic functions through two receptors, NPFFR1 and NPFFR2. The hypothalamic-pituitary-adrenal (HPA) axis participates in physiological stress response by increasing circulating glucocorticoid levels and modulating emotional responses. Other RFamide peptides, including neuropeptide AF, neuropeptide SF and RFamide related peptide also target NPFFR1 or NPFFR2, and have been reported to activate the HPA axis and induce anxiety- or depression-like behaviors. However, little is known about the action of NPFF on HPA axis activity and anxiety-like behaviors, and the role of the individual receptors remains unclear. In this study, NPFFR2 agonists were used to examine the role of NPFFR2 in activating the HPA axis in rodents. Administration of NPFFR2 agonists, dNPA (intracerebroventricular, ICV) and AC-263093 (intraperitoneal, IP), time-dependently (in rats) and dose-dependently (in mice) increased serum corticosteroid levels and the effects were counteracted by the NPFF receptor antagonist, RF9 (ICV), as well as corticotropin-releasing factor (CRF) antagonist, α-helical CRF(9-41) (intravenous, IV). Treatment with NPFFR2 agonist (AC-263093, IP) increased c-Fos protein expression in the hypothalamic paraventricular nucleus and induced an anxiogenic effect, which was evaluated in mice using an elevated plus maze. These findings reveal, for the first time, that the direct action of hypothalamic NPFFR2 stimulates the HPA axis and triggers anxiety-like behaviors. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
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1074 KiB  
Article
Effects of Pup Separation on Stress Response in Postpartum Female Rats
by Manu Kalyani, Phyllis Callahan, James M. Janik and Haifei Shi
Int. J. Mol. Sci. 2017, 18(7), 1370; https://doi.org/10.3390/ijms18071370 - 27 Jun 2017
Cited by 12 | Viewed by 4685
Abstract
There is a complex collection of neuroendocrine function during the postpartum period. Prolactin (PRL) released by suckling stimulus and its PRL receptors (PRL-R) in the central nervous system (CNS) are involved in hyporesponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in lactating mammals including rodents [...] Read more.
There is a complex collection of neuroendocrine function during the postpartum period. Prolactin (PRL) released by suckling stimulus and its PRL receptors (PRL-R) in the central nervous system (CNS) are involved in hyporesponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in lactating mammals including rodents and humans. It is not clear how long it takes to reestablish the attenuated HPA axis activity of lactating rats to a pre-pregnancy state after pup separation. We first tested the hypothesis that HPA axis activity in response to an acute stress in postpartum rats would return to a pre-pregnancy state after pup separation. Restraint stress for 30 min was performed at the end of pup separation as an acute stressor. Plasma levels of corticosterone (CORT) were measured following restraint stress or no-stress (control) in virgin rats and postpartum rats housed with their pups or with pup removal for different periods of time of one hour, 24 h, or eight days. We then tested the hypothesis that circulating PRL level and CNS PRL-R gene expression were involved in mediating the acute stress response in postpartum rats. Plasma levels of PRL and PRL-R mRNA levels in the choroid plexus of the CNS were determined in both no-stress and stress, virgin rats, and postpartum rats housed with their pups or with pup removal for various periods, and their correlation with plasma CORT levels was assessed. The results demonstrated that PRL levels declined to virgin state in all postpartum rats separated from their pups, including the dams with one-hour pup separation. Stress-induced HPA activity dampened in lactating rats housed with pups, and returned to the pre-pregnancy state after 24 h of pup separation when both circulating PRL level and CNS PRL-R expression were restored to a pre-pregnancy state. Additionally, basal plasma CORT and CNS PRL-R expression were significantly correlated in rats with various pup status. This study suggested that stress-induced HPA activation occurred when PRL-R expression was similar to the level of virgin females, indicating that PRL-R upregulation contributes to an attenuated HPA response to acute stress. Understanding neuroendocrine responses to stress during the postpartum period is critical to understand postpartum-related neuropsychiatric illnesses and to maintain mental health in postpartum women. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
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Review

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238 KiB  
Review
The Hypothalamic–Pituitary Axis and Autoantibody Related Disorders
by Cristina Cocco, Carla Brancia, Giulia Corda and Gian-Luca Ferri
Int. J. Mol. Sci. 2017, 18(11), 2322; https://doi.org/10.3390/ijms18112322 - 03 Nov 2017
Cited by 21 | Viewed by 4945
Abstract
This review summarized different studies reporting the presence of autoantibodies reacting against cells of the pituitary (APAs) and/or hypothalamus (AHAs). Both APAs and AHAs have been revealed through immunofluorescence using different kinds of substrates. Autoantibodies against gonadotropic cells were mainly found in patients [...] Read more.
This review summarized different studies reporting the presence of autoantibodies reacting against cells of the pituitary (APAs) and/or hypothalamus (AHAs). Both APAs and AHAs have been revealed through immunofluorescence using different kinds of substrates. Autoantibodies against gonadotropic cells were mainly found in patients affected by cryptorchidism and hypogonadotropic hypogonadism while those against prolactin cells were found in different kinds of patients, the majority without pituitary abnormalities. APAs to growth hormone (GH) cells have been associated with GH deficiency while those against the adrenocorticotropic cells have distinguished central Cushing’s disease patients at risk of incomplete cure after surgical adenoma removal. AHAs to vasopressin cells have identified patients at risk of developing diabetes insipidus. APAs have been also found together with AHAs in patients affected by idiopathic hypopituitarism, but both were also present in different kinds of patients without abnormalities of the hypothalamic–pituitary axis. Despite some data being promising, the clinical use of pituitary and hypothalamus autoantibodies is still limited by the low diagnostic sensitivity, irreproducibility of the results, and the absence of autoantigen/s able to discriminate the autoimmune reaction involving the pituitary or the hypothalamus from the other autoimmune states. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
515 KiB  
Review
Relation among Aromatase P450 and Tumoral Growth in Human Prolactinomas
by María José García-Barrado, Enrique J. Blanco, María Carmen Iglesias-Osma, Marta Carretero-Hernández, Leonardo Catalano-Iniesta, Virginia Sanchez-Robledo, Manuel Carretero, Julio Joaquín Herrero, Sixto Carrero and José Carretero
Int. J. Mol. Sci. 2017, 18(11), 2299; https://doi.org/10.3390/ijms18112299 - 01 Nov 2017
Cited by 11 | Viewed by 5853
Abstract
The pituitary gland is part of hypothalamic-pituitary–gonadal axis, which controls development, reproduction, and aging in humans and animals. In addition, the pituitary gland is regulated mainly by hormones and neurotransmitters released from the hypothalamus and by systemic hormones secreted by target glands. Aromatase [...] Read more.
The pituitary gland is part of hypothalamic-pituitary–gonadal axis, which controls development, reproduction, and aging in humans and animals. In addition, the pituitary gland is regulated mainly by hormones and neurotransmitters released from the hypothalamus and by systemic hormones secreted by target glands. Aromatase P450, the enzyme responsible for the catabolization of aromatizable androgens to estrogens, is expressed in different parts of body, including the pituitary gland. Moreover, aromatase P450 is involved in sexual dimorphism where alteration in the level of aromatase can initiate a number of diseases in both genders. On the other hand, the direct actions of estrogens, mainly estradiol, are well known for stimulating prolactin release. Numerous studies have shown that changes in the levels of estrogens, among other factors, have been implicated in the genesis and development of prolactinoma. The pituitary gland can produce estradiol locally in several types of endocrine cells, and it is possible that aromatase could be responsible for the maintenance of the population of lactotroph cells and the modulation of the action of central or peripheral regulators. Aromatase overexpression due to inappropriate gene regulation has clinical effects such as the pathogenesis of prolactinomas. The present study reports on the synthesis of pituitary aromatase, its regulation by gonadal steroids, and the physiological roles of aromatase on pituitary endocrine cells. The involvement of aromatase in the pathogenesis of pituitary tumors, mainly prolactinomas, through the auto-paracrine production of estradiol is reviewed. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
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878 KiB  
Review
Stress and the HPA Axis: Balancing Homeostasis and Fertility
by Dana N. Joseph and Shannon Whirledge
Int. J. Mol. Sci. 2017, 18(10), 2224; https://doi.org/10.3390/ijms18102224 - 24 Oct 2017
Cited by 150 | Viewed by 26167
Abstract
An organism’s reproductive fitness is sensitive to the environment, integrating cues of resource availability, ecological factors, and hazards within its habitat. Events that challenge the environment of an organism activate the central stress response system, which is primarily mediated by the hypothalamic–pituitary–adrenal (HPA) [...] Read more.
An organism’s reproductive fitness is sensitive to the environment, integrating cues of resource availability, ecological factors, and hazards within its habitat. Events that challenge the environment of an organism activate the central stress response system, which is primarily mediated by the hypothalamic–pituitary–adrenal (HPA) axis. The regulatory functions of the HPA axis govern the cardiovascular and metabolic system, immune functions, behavior, and reproduction. Activation of the HPA axis by various stressors primarily inhibits reproductive function and is able to alter fetal development, imparting a biological record of stress experienced in utero. Clinical studies and experimental data indicate that stress signaling can mediate these effects through direct actions in the brain, gonads, and embryonic tissues. This review focuses on the mechanisms by which stress activation of the HPA axis impacts fertility and fetal development. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
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1148 KiB  
Review
Treatment with Synthetic Glucocorticoids and the Hypothalamus-Pituitary-Adrenal Axis
by Rosa Maria Paragliola, Giampaolo Papi, Alfredo Pontecorvi and Salvatore Maria Corsello
Int. J. Mol. Sci. 2017, 18(10), 2201; https://doi.org/10.3390/ijms18102201 - 20 Oct 2017
Cited by 110 | Viewed by 12654
Abstract
Chronic glucocorticoid (GC) treatment represents a widely-prescribed therapy for several diseases in consideration of both anti-inflammatory and immunosuppressive activity but, if used at high doses for prolonged periods, it can determine the systemic effects characteristic of Cushing’s syndrome. In addition to signs and [...] Read more.
Chronic glucocorticoid (GC) treatment represents a widely-prescribed therapy for several diseases in consideration of both anti-inflammatory and immunosuppressive activity but, if used at high doses for prolonged periods, it can determine the systemic effects characteristic of Cushing’s syndrome. In addition to signs and symptoms of hypercortisolism, patients on chronic GC therapy are at risk to develop tertiary adrenal insufficiency after the reduction or the withdrawal of corticosteroids or during acute stress. This effect is mediated by the negative feedback loop on the hypothalamus-pituitary-adrenal (HPA) axis, which mainly involves corticotropin-release hormone (CRH), which represents the most important driver of adrenocorticotropic hormone (ACTH) release. In fact, after withdrawal of chronic GC treatment, reactivation of CRH secretion is a necessary prerequisite for the recovery of the HPA axis. In addition to the well-known factors which regulate the degree of inhibition of the HPA during synthetic GC therapy (type of compound, method of administration, cumulative dose, duration of the treatment, concomitant drugs which can increase the bioavailability of GCs), there is a considerable variation in individual physiology, probably related to different genetic profiles which regulate GC receptor activity. This may represent an interesting basis for possible future research fields. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
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1256 KiB  
Review
Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System
by Natalie G. Burford, Natalia A. Webster and Diana Cruz-Topete
Int. J. Mol. Sci. 2017, 18(10), 2150; https://doi.org/10.3390/ijms18102150 - 16 Oct 2017
Cited by 98 | Viewed by 24081
Abstract
The collective of endocrine organs acting in homeostatic regulation—known as the hypothalamic-pituitary-adrenal (HPA) axis—comprises an integration of the central nervous system as well as peripheral tissues. These organs respond to imminent or perceived threats that elicit a stress response, primarily culminating in the [...] Read more.
The collective of endocrine organs acting in homeostatic regulation—known as the hypothalamic-pituitary-adrenal (HPA) axis—comprises an integration of the central nervous system as well as peripheral tissues. These organs respond to imminent or perceived threats that elicit a stress response, primarily culminating in the release of glucocorticoids into the systemic circulation by the adrenal glands. Although the secretion of glucocorticoids serves to protect and maintain homeostasis in the typical operation at baseline levels, inadequate regulation can lead to physiologic and psychologic pathologies. The cardiovascular system is especially susceptible to prolonged dysregulation of the HPA axis and glucocorticoid production. There is debate about whether cardiovascular health risks arise from the direct detrimental effects of stress axis activation or whether pathologies develop secondary to the accompanying metabolic strain of excess glucocorticoids. In this review, we will explore the emerging research that indicates stress does have direct effects on the cardiovascular system via the HPA axis activation, with emphasis on the latest research on the impact of glucocorticoids signaling in the vasculature and the heart. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
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1234 KiB  
Review
Association between Stress and the HPA Axis in the Atopic Dermatitis
by Tzu-Kai Lin, Lily Zhong and Juan Luis Santiago
Int. J. Mol. Sci. 2017, 18(10), 2131; https://doi.org/10.3390/ijms18102131 - 12 Oct 2017
Cited by 64 | Viewed by 12283
Abstract
The hypothalamic–pituitary–adrenal (HPA) axis is one of the body’s neuroendocrine networks that responds to psychological stress (PS). In the skin, there exists a peripheral HPA axis similar to the central axis. Glucocorticoids (GCs) are key effector molecules of the HPA axis and are [...] Read more.
The hypothalamic–pituitary–adrenal (HPA) axis is one of the body’s neuroendocrine networks that responds to psychological stress (PS). In the skin, there exists a peripheral HPA axis similar to the central axis. Glucocorticoids (GCs) are key effector molecules of the HPA axis and are essential for cutaneous homeostasis. Atopic dermatitis (AD) is a condition typically characterized by a chronic relapsing course that often results in PS. HPA dysfunction is present in AD patients by the decreased response of GCs elevation to stress as compared to those unaffected by AD. Nevertheless, in skin, acute PS activates several metabolic responses that are of immediate benefit to the host. During the acute phase of PS, increased endogenous GCs have been shown to provide benefit rather than by aggravating cutaneous inflammatory dermatoses. However, a chronic T helper cell type 2 (Th2) predominant cytokine profile acts as a negative feedback loop to blunt the HPA axis response in AD. In this article, we reviewed the role of CRF, pro-opiomelanocortin (POMC)-derived peptides, GCs of the HPA, and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in AD, with a discussion of the pathogenetic mechanisms of inflammation and skin barrier functions, including antimicrobial defense, and their association with PS. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
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472 KiB  
Review
Association between Mastication, the Hippocampus, and the HPA Axis: A Comprehensive Review
by Kagaku Azuma, Qian Zhou, Masami Niwa and Kin-ya Kubo
Int. J. Mol. Sci. 2017, 18(8), 1687; https://doi.org/10.3390/ijms18081687 - 03 Aug 2017
Cited by 61 | Viewed by 10955
Abstract
Mastication is mainly involved in food intake and nutrient digestion with the aid of teeth. Mastication is also important for preserving and promoting general health, including hippocampus-dependent cognition. Both animal and human studies indicate that mastication influences hippocampal functions through the end product [...] Read more.
Mastication is mainly involved in food intake and nutrient digestion with the aid of teeth. Mastication is also important for preserving and promoting general health, including hippocampus-dependent cognition. Both animal and human studies indicate that mastication influences hippocampal functions through the end product of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoid (GC). Epidemiologic studies suggest that masticatory dysfunction in aged individuals, such as that resulting from tooth loss and periodontitis, acting as a source of chronic stress, activates the HPA axis, leading to increases in circulating GCs and eventually inducing various physical and psychological diseases, such as cognitive impairment, cardiovascular disorders, and osteoporosis. Recent studies demonstrated that masticatory stimulation or chewing during stressful conditions suppresses the hyperactivity of the HPA axis via GCs and GC receptors within the hippocampus, and ameliorates chronic stress-induced hippocampus-dependent cognitive deficits. Here, we provide a comprehensive overview of current research regarding the association between mastication, the hippocampus, and HPA axis activity. We also discuss several potential molecular mechanisms involved in the interactions between mastication, hippocampal function, and HPA axis activity. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
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Brief Report
Cortisol Awakening Response, Internalizing Symptoms, and Life Satisfaction in Emerging Adults
by Li Shen Chong, Michelle Thai, Kathryn R. Cullen, Kelvin O. Lim and Bonnie Klimes-Dougan
Int. J. Mol. Sci. 2017, 18(12), 2501; https://doi.org/10.3390/ijms18122501 - 27 Nov 2017
Cited by 8 | Viewed by 4315
Abstract
The cortisol awakening response (CAR) has been associated with depression and a broader range of internalizing problems. Emerging adulthood is characterized by numerous stressful transitional life events. Furthermore, the functioning of the neurobiological stress system changes across development. These considerations underscore the importance [...] Read more.
The cortisol awakening response (CAR) has been associated with depression and a broader range of internalizing problems. Emerging adulthood is characterized by numerous stressful transitional life events. Furthermore, the functioning of the neurobiological stress system changes across development. These considerations underscore the importance of evaluating the physiological stress system in emerging adults in identifying the extent to which cortisol levels vary with risk and protective factors for mental health. The present study evaluated the association between internalizing symptoms and perceived life satisfaction with CAR in 32 young adults. Three saliva samples were collected to measure cortisol levels upon awakening and participants completed the Depression Anxiety Stress Scale (DASS) and Satisfaction with Life Scale (SWLS). Results show a significant positive correlation between area under the curve for CAR with internalizing symptoms (DASS total) and the DASS-depression subscale, but not with life satisfaction. Study limitations, implications, and future directions for these finding were discussed. Full article
(This article belongs to the Special Issue Role of the Hypothalamo–Pituitary–Adrenal (HPA) Axis in Health and Disease)
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