Oxytocin modulates HPA axis activity and hormone response to stress in rats chronically treated with corticosterone

AbstractThe major endocrine response to stress occurs via activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading ultimately to increases in circulating glucocorticoids, which are essential for the metabolic adaptation to stress. The major players in the HPA axis are the hypothalamic neuropeptide, corticotropin releasing hormone (CRH), the pituitary hormone adrenocorticotropic hormone, and the negative feedback effects of adrenal glucocorticoids. In addition, a number of other neuropeptides, including vasopressin (VP), angiotensin II, oxytocin, pituitary adenylate cyclase activating peptide, orexin and cholecystokinin, and nesfatin can affect HPA axis activity by influencing the expression and secretion of CRH, and also by modulating pituitary corticotroph function or adrenal steroidogenesis. Of these peptides, VP co-secreted with CRH from axonal terminals in the external zone of the median eminence plays a prominent role by potentiating the stimulatory effect of CRH and by increasing the number of pituitary corticotrophs during chronic challenge. Although the precise role and significance of many of these neuropeptides in regulating HPA axis activity requires further investigation, it is likely that they are part of a multifactorial system mediating the fine tuning of HPA axis activity during adaptation to a variety of physiological and stressful conditions.

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Programming of the Hypothalamus-Pituitary-Adrenal Axis by Very Preterm Birth

Annals of Nutrition and Metabolism ◽

10.1159/000456040 ◽

2017 ◽

Vol 70 (3) ◽

pp. 170-174 ◽

Cited By ~ 16

Author(s):

Martijn J.J. Finken ◽

Bibian van der Voorn ◽

Jonneke J. Hollanders ◽

Charlotte A. Ruys ◽

Marita de Waard ◽

...

Keyword(s):

Hpa Axis ◽

Relative Adrenal Insufficiency ◽

Very Preterm ◽

Adrenocortical Response ◽

Adrenal Hyperandrogenism ◽

Response To Stress ◽

Multiple Levels ◽

Internalizing Problem ◽

Hpa Axis Activity ◽

Preterm Newborns

Background: Many very preterm (i.e., <32 weeks of gestation) newborns fail to mount an adequate adrenocortical response to stress or illness, termed relative adrenal insufficiency. Conversely, later in life these infants show features of increased glucocorticoid bioactivity, such as abdominal adiposity, insulin resistance, raised blood pressure, shorter stature and internalizing problem behavior. Summary: Studies suggested that very preterm newborns have impairments along multiple levels of the hypothalamus-pituitary-adrenal (HPA) axis. Among the impairment were defects in: (1) the pituitary responsiveness to exogenous corticotropin-releasing hormone, (2) 11β-hydroxylase activity, and (3) the interconversion between cortisol and inert cortisone. There is some evidence suggesting that later in life these infants have an increased basal secretion rate of cortisol and adrenal hyperandrogenism. However, the response to acute (psychosocial) stress was blunted rather than enhanced in them. The mechanisms explaining this switch in HPA axis activity are complex and not yet fully understood. Key Messages: Very preterm newborns have several impairments along the HPA axis that could impede an adequate adrenocortical response to stress or illness. Later in life, these infants are predisposed to increased HPA axis activity, which could partially explain their phenotype.

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Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain

Journal of Endocrinology ◽

10.1677/joe-08-0509 ◽

2009 ◽

Vol 202 (1) ◽

pp. 87-97 ◽

Cited By ~ 75

Author(s):

Miroslav Adzic ◽

Jelena Djordjevic ◽

Ana Djordjevic ◽

Ana Niciforovic ◽

Constantinos Demonacos ◽

...

Keyword(s):

Glucocorticoid Receptor ◽

Chronic Stress ◽

Hpa Axis ◽

Transcriptional Activity ◽

Subcellular Location ◽

Wistar Rat ◽

High Serum ◽

Response To Stress ◽

Neurotropic Factor ◽

Hpa Axis Activity

Chronic stress and impaired glucocorticoid receptor (GR) feedback are important factors for the compromised hypothalamic–pituitary–adrenal (HPA) axis activity. We investigated the effects of chronic 21 day isolation of Wistar rats on the extrinsic negative feedback part of HPA axis: hippocampus (HIPPO) and prefrontal cortex (PFC). In addition to serum corticosterone (CORT), we followed GR subcellular localization, GR phosphorylation at serine 232 and serine 246, expression of GR regulated genes: GR, CRF and brain-derived neurotropic factor (BDNF), and activity of c-Jun N-terminal kinase (JNK) and Cdk5 kinases that phosphorylate GR. These parameters were also determined in animals subjected to acute 30 min immobilization, which was taken as ‘normal’ adaptive response to stress. In isolated animals, we found decreased CORT, whereas in animals exposed to acute immobilization, CORT was markedly increased. Even though the GR was predominantly localized in the nucleus of HIPPO and PFC in acute, but not in chronic stress, the expression of GR, CRF, and BDNF genes was similarly regulated under both acute and chronic stresses. Thus, the transcriptional activity of GR under chronic isolation did not seem to be exclusively dependent on high serum CORT levels nor on the subcellular location of the GR protein. Rather, it resulted from the increased Cdk5 activation and phosphorylation of the nuclear GR at serine 232 and the decreased JNK activity reflected in decreased phosphorylation of the nuclear GR at serine 246. Our study suggests that this nuclear isoform of hippocampal and cortical GR may be related to hypocorticism i.e. HPA axis hypoactivity under chronic isolation stress.

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Effects of L-3,4-dihydroxyphenylalanine (L-Dopa) Treatment in the Neuroendocrine Response to Stress

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.136 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A67-A68

Author(s):

Santiago Jordi Orrillo ◽

Mercedes Imsen ◽

Alfonsina Lizarraga ◽

Ana Clara Romero ◽

Fernanda De Fino ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Stress Response ◽

Hpa Axis ◽

Sympathetic Nerves ◽

Serum Levels ◽

Male Wistar Rats ◽

Response To Stress ◽

Behavioural Tests ◽

Hpa Axis Activity

Abstract Stressful stimuli evoke a complex response mediated by two systems: the Sympathetic-Adreno-Medullar (SAM) axis and the Hypothalamus-Pituitary-Adrenal (HPA) axis. Among the factors involved in stress, glucocorticoids and catecholamines secreted from the adrenal glands and sympathetic nerves are the main effectors of the physiological adaptations to stressors. Besides these, prolactin (PRL) is another hormone secreted under stress conditions. Catecholamines are synthesized from the hydroxylated precursor L-Dopa. This agent is commonly used for the treatment of Parkinson’s disease and it would act as a neurotransmitter per se. On the other hand, it has been suggested that HPA axis dysregulation is a potential risk factor for the development of depression. In line with this, several studies reported that L-Dopa treatment may alter the serum levels of ACTH, PRL, and glucocorticoids in parkinsonian patients and Parkinson’s disease animal models. In the present study, we determined whether the chronic treatment with L-Dopa altered the stress response inducing depressive-like behaviours. Adult male Wistar rats were treated orally during 24 days with LEBOCAR® - commercial formulation of L-Dopa (75 mg/day) and Carbidopa (7.5 mg/day) - in drinking water. Animals were stressed by immobilization during the last 9 days of treatment and depressive-like behaviours were assessed by the sucrose intake and forced swimming tests. Behavioural tests showed no signs of depressive-like behaviours in the LEBOCAR®-treated and/or stressed rats. We next explored the SAM axis reactivity. Circulating noradrenaline and adrenaline increased in rats treated with LEBOCAR® (p<0.05; HPLC). Also, the adrenals from stressed animals showed higher content of adrenaline (p<0.05). Then, we studied the HPA axis activity. Chronically stressed rats displayed a lower ACTH secretion (ELISA) and a downregulation of POMC expression (qPCR) in the anterior pituitary (p<0.05). In addition, LEBOCAR® treatment induced a reduction in serum ACTH and POMC levels (p<0.05). As expected, serum corticosterone (ELISA) enhanced under chronic stress, an effect that was inhibited by treatment with LEBOCAR® (p<0.05). Finally, pituitary PRL gene expression (qPCR) was downregulated by LEBOCAR® treatment with a more pronounced effect when rats were also stressed (p<0.05). Our results suggest that L-Dopa alters the neuroendocrine stress response enhancing SAM axis reactivity and reducing HPA axis activity and PRL expression.

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Social rearing effects on HPA axis activity over early development and in response to stress in rhesus monkeys

Developmental Psychobiology ◽

10.1002/dev.420260802 ◽

1993 ◽

Vol 26 (8) ◽

pp. 433-446 ◽

Cited By ~ 98

Author(s):

A. S. Clarke

Keyword(s):

Early Development ◽

Hpa Axis ◽

Rhesus Monkeys ◽

Response To Stress ◽

Hpa Axis Activity ◽

Rearing Effects

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Sensitivity to stress-induced reproductive dysfunction is associated with a selective but not a generalized increase in activity of the adrenal axis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00223.2010 ◽

2011 ◽

Vol 300 (1) ◽

pp. E28-E36 ◽

Cited By ~ 23

Author(s):

S. M. Herod ◽

A. M. Dettmer ◽

M. A. Novak ◽

J. S. Meyer ◽

J. L. Cameron

Keyword(s):

Social Environment ◽

Hpa Axis ◽

Life Stress ◽

Metabolic Stress ◽

Reproductive Dysfunction ◽

Adrenal Axis ◽

Response To Stress ◽

Increased Sensitivity ◽

As Stress ◽

Hpa Axis Activity

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.

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