Testing the developmental hypothesis of the HPA axis in a tropical passerine: Dampened corticosterone response and faster negative feedback in nestling lance-tailed manakins (Chiroxiphia lanceolata)

ABSTRACT Adjuvant arthritis (AA) in the rat leads to chronic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis and the loss of its diurnal rhythmicity. We have investigated the effects of adrenalectomy (ADX) and different levels of corticosterone replacement upon plasma ACTH levels and anterior pituitary pro-opiomelanocortin (POMC), GH and prolactin mRNAs during the development of AA. In control ADX animals, we observed the negative feedback effects of exogenous corticosterone on plasma ACTH and anterior pituitary POMC mRNA. In the ADX animal with AA, however, the increased POMC mRNA which was observed was not reduced by exogenous corticosterone on day 7 of AA, although the negative feedback effect of corticosterone on plasma ACTH was intact. On day 14, however, even high dose corticosterone replacement failed to have a significant feedback effect on the raised levels of plasma ACTH. In control ADX animals, corticosterone replacement resulted in increased anterior pituitary GH mRNA and reduced prolactin mRNA. In contrast, in ADX animals with AA, GH mRNA was reduced and there was a further decrease in prolactin mRNA. In these animals, corticosterone replacement did not affect GH or prolactin mRNA expression. These data demonstrate a disruption of the normal mechanisms underlying feedback inhibition of the HPA axis by glucocorticoids during AA. Similarly, the glucocorticoid-dependent regulation of GH and prolactin mRNA expression is altered in AA.

Download Full-text

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

Endocrinology ◽

10.1210/en.2008-0238 ◽

2008 ◽

Vol 149 (12) ◽

pp. 6366-6377 ◽

Cited By ~ 39

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.

Download Full-text

Inflammatory Pain and Corticosterone Response in Infant Rats: Effect of 5-HT1A Agonist Buspirone Prior to Gestational Stress

Mediators of Inflammation ◽

10.1155/2013/915189 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Irina P. Butkevich ◽

Viktor A. Mikhailenko ◽

Tat'yana R. Bagaeva ◽

Elena A. Vershinina ◽

Anna Maria Aloisi ◽

...

Keyword(s):

Hpa Axis ◽

Inflammatory Pain ◽

Formalin Test ◽

Corticosterone Level ◽

Plasma Corticosterone ◽

Male Rats ◽

Plasma Corticosterone Level ◽

Infant Rats ◽

Corticosterone Response ◽

Gestational Stress

Our researches have shown that gestational stress causes exacerbation of inflammatory pain in the offspring; the maternal 5-HT1A agonist buspirone before the stress prevents the adverse effect. The serotonergic system and hypothalamo-pituitary-adrenal (HPA) axis are closely interrelated. However, interrelations between inflammatory pain and the HPA axis during the hyporeactive period of the latter have not been studied. The present research demonstrates that formalin-induced pain causes a gradual and prolonged increase in plasma corticosterone level in 7-day-old male rats; twenty-four hours after injection of formalin, the basal corticosterone level still exceeds the initial basal corticosterone value. Chronic treatments of rat dams with buspirone before restraint stress during gestation normalize in the offspring pain-like behavior and induce during the acute phase in the formalin test the stronger corticosterone increase as compared to the stress hormonal elevation in animals with other prenatal treatments. Negative correlation between plasma corticosterone level and the number of flexes+shakes is revealed in buspirone+stress rats. The new data enhance the idea about relativity of the HPA axis hyporeactive period and suggest that maternal buspirone prior to stress during gestation may enhance an adaptive mechanism of the inflammatory nociceptive system in the infant male offspring through activation of the HPA axis peripheral link.

Download Full-text

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

Journal of Endocrinology ◽

10.1530/joe-13-0062 ◽

2013 ◽

Vol 219 (1) ◽

pp. 21-27 ◽

Cited By ~ 13

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.

Download Full-text

Maternal glucocorticoids do not influence HPA axis activity or behavior of juvenile wild North American red squirrels

10.1101/2020.09.02.280065 ◽

2020 ◽

Author(s):

Sarah E Westrick ◽

Freya van Kesteren ◽

Stan Boutin ◽

Jeffrey E Lane ◽

Andrew G McAdam ◽

...

Keyword(s):

Hpa Axis ◽

Negative Feedback ◽

North American ◽

High Density ◽

Early Lactation ◽

Red Squirrels ◽

North American Red Squirrels ◽

And Behavior ◽

Hpa Axis Activity ◽

The Impact

AbstractEnvironmental factors experienced during development can affect the physiology and behavior of offspring. Maternal glucocorticoids (GCs) may convert environmental cues experienced by the mother into a cue triggering adaptive developmental plasticity in offspring. In North American red squirrels (Tamiasciurus hudsonicus), females exhibit increases in GCs when conspecific density is elevated, and selection favors more aggressive and perhaps more active mothers under high density conditions. We experimentally elevated maternal GCs during gestation or early lactation to test the hypothesis that elevated maternal GCs cause shifts in offspring aggression and activity that may prepare them for high density conditions. When offspring were weaned, we measured two behavioral traits (activity and aggression) using a standardized behavioral assay. Because maternal GCs may influence offspring hypothalamic-pituitary-adrenal (HPA) axis activity and HPA axis activity may in turn affect offspring behavior, we also measured the impact of our treatments on offspring HPA axis activity (adrenal reactivity and negative feedback) and the association between offspring HPA axis activity and behavior. Increased maternal GCs during lactation, but not gestation, only slightly elevated activity levels in offspring. Offspring aggression, adrenal reactivity, and negative feedback did not differ between GC-treated and control groups. Offspring with higher adrenal reactivity did exhibit lower aggression, but the relationship between adrenal reactivity and aggression was not affected by treatment with maternal GCs. These results suggest maternal GCs during gestation or early lactation alone may not be a sufficient cue to produce changes in behavioral and physiological stress responses in offspring in natural populations.Summary StatementWe found maternal glucocorticoid levels do not influence offspring personality or HPA axis dynamics in North American red squirrels. Regardless of maternal glucocorticoid treatment, more aggressive squirrels exhibited lower adrenal reactivity.

Download Full-text

60 YEARS OF NEUROENDOCRINOLOGY: Glucocorticoid dynamics: insights from mathematical, experimental and clinical studies

Journal of Endocrinology ◽

10.1530/joe-15-0132 ◽

2015 ◽

Vol 226 (2) ◽

pp. T55-T66 ◽

Cited By ~ 29

Author(s):

Francesca Spiga ◽

Jamie J Walker ◽

Rita Gupta ◽

John R Terry ◽

Stafford L Lightman

Keyword(s):

Hpa Axis ◽

Negative Feedback ◽

Clinical Studies ◽

Dynamic Processes ◽

Hypothalamic Pituitary Adrenal ◽

Adrenal Axis ◽

Pituitary Adrenal Axis

A pulsatile pattern of secretion is a characteristic of many hormonal systems, including the glucocorticoid-producing hypothalamic–pituitary–adrenal (HPA) axis. Despite recent evidence supporting its importance for behavioral, neuroendocrine and transcriptional effects of glucocorticoids, there has been a paucity of information regarding the origin of glucocorticoid pulsatility. In this review we discuss the mechanisms regulating pulsatile dynamics of the HPA axis, and how these dynamics become disrupted in disease. Our recent mathematical, experimental and clinical studies show that glucocorticoid pulsatility can be generated and maintained by dynamic processes at the level of the pituitary–adrenal axis, and that an intra-adrenal negative feedback may contribute to these dynamics.

Download Full-text

Stress sensitivity is increased in transgenic rats with low brain angiotensinogen

Journal of Endocrinology ◽

10.1677/joe-09-0363 ◽

2009 ◽

Vol 204 (1) ◽

pp. 85-92 ◽

Cited By ~ 14

Author(s):

Helge Müller ◽

Juliane Kröger ◽

Olaf Jöhren ◽

Silke Szymczak ◽

Michael Bader ◽

...

Keyword(s):

Blood Pressure ◽

Hpa Axis ◽

Stress Responses ◽

Forced Swim Test ◽

Stress Sensitivity ◽

Transgenic Rat ◽

Mrna Levels ◽

Stress Tests ◽

Corticosterone Response ◽

Corticosterone Release

AT1 blockers attenuate hypothalamo-pituitary–adrenal (HPA) axis reactivity in hypertension independently of their potency to lower blood pressure. A reduced pituitary sensitivity to CRH and a downregulation of hypothalamic CRH expression have been suggested to influence HPA axis activity during chronic AT1 blockade. This study was aimed at confirming the role of central angiotensin II in regulating HPA reactivity by using the transgenic rat TGR(ASrAOGEN), a model featuring low levels of brain angiotensinogen. Different stress tests were performed to determine HPA reactivity in TGR(ASrAOGEN) and appropriate controls. In TGR(ASrAOGEN), blood pressure was diminished compared to controls. The corticosterone response to a CRH or ACTH challenge and a forced swim test was more distinct in TGR(ASrAOGEN) than it was in controls and occurred independently of a concurrent enhancement in ACTH. Using quantitative real-time PCR, we found increased mRNA levels of melanocortin 2 (Mc2r) and AT2 receptors (Agtr2) in the adrenals of TGR(ASrAOGEN), whereas mRNA levels of Crh, Pomc, and AT1 receptors (Agtr1) remained unchanged in hypothalami and pituitary glands. Since stress responses were increased rather than attenuated in TGR(ASrAOGEN), we conclude that the reduced HPA reactivity during AT1 blockade could not be mimicked in a specific transgenic rat model featuring a centrally inactivated renin–angiotensin–aldosterone system. The ACTH independency of the enhanced corticosterone release during CRH test and the enhanced corticosterone response to ACTH rather indicates an adrenal mechanism. The upregulation of adrenal MC2 and AT2 receptors seems to be involved in the stimulated facilitation of adrenal corticosterone release for effectuating the stimulated stress responses.

Download Full-text

Disruption of mineralocorticoid receptor function increases corticosterone responding to a mild, but not moderate, psychological stressor

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00521.2004 ◽

2005 ◽

Vol 288 (6) ◽

pp. E1082-E1088 ◽

Cited By ~ 35

Author(s):

Thaddeus W. W. Pace ◽

Robert L. Spencer

Keyword(s):

Hpa Axis ◽

Negative Feedback ◽

Glucocorticoid Receptors ◽

Feedback Regulation ◽

Sprague Dawley ◽

Negative Feedback Regulation ◽

Novel Environment ◽

Sterile Saline ◽

Sprague Dawley Rats ◽

Psychological Stressor

Glucocorticoid negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis is mediated by corticosteroid receptors. It is widely thought that during stress, glucocorticoid receptors (GR) are essential for this negative feedback. In contrast, mineralocorticoid receptors (MR) are associated with HPA axis regulation in basal, nonstress conditions. Notions about the relative roles of MR and GR for HPA axis regulation during stressor challenge may not be complete. Recent work in our laboratory suggests that previous estimates of MR occupancy at resting plasma levels of corticosterone (CORT) may be overestimated. It is possible that a significant number of MR may be available to mediate negative feedback during stressor challenge. We hypothesized that this may be especially the case during mild stressor challenge when the plasma CORT response is weak. In the present studies, adult male Sprague-Dawley rats were first treated systemically or centrally with the selective MR antagonist RU28318 (50 mg/kg sc or 500 ng·10 μl−1·2 h−1 icv) or vehicle (300 μl propylene glycol sc or 10 μl/2 h sterile saline icv) and then challenged with 60-min novel environment or restraint. In vehicle controls, restraint resulted in a greater plasma CORT response than novel environment. Both systemic and central treatment with RU28318 significantly increased CORT responding to novel environment relative to vehicle controls. However, RU28318 treatment did not increase the CORT response to restraint. These data suggest that MR may be necessary for glucocorticoid regulation of HPA axis activity during mild stressors, but not during stressors that result in a more robust CORT response.

Download Full-text

Neonatal monosodium glutamate treatment alters both the activity and the sensitivity of the rat hypothalamo-pituitary-adrenocortical axis

Journal of Endocrinology ◽

10.1677/joe.0.1410497 ◽

1994 ◽

Vol 141 (3) ◽

pp. 497-503 ◽

Cited By ~ 23

Author(s):

P J Larsen ◽

J D Mikkelsen ◽

D Jessop ◽

S L Lightman ◽

H S Chowdrey

Keyword(s):

Hpa Axis ◽

Restraint Stress ◽

Acute Stress ◽

Monosodium Glutamate ◽

Plasma Corticosterone ◽

Mrna Levels ◽

Plasma Acth ◽

Corticotrophin Releasing Factor ◽

Acute And Chronic Stress ◽

Corticosterone Response

Abstract We have investigated the effects of monosodium glutamate (MSG) lesioning of the arcuate nucleus on both central and peripheral components of the hypothalamo-pituitary-adrenocortical (HPA) axis under basal conditions and under acute and chronic stress. Plasma ACTH levels were lower in MSG-lesioned rats (27 ± 7 pg/ml) compared with controls (71 ± 18 pg/ml) while corticosterone levels were elevated (523 ± 84 ng/ml compared with 176 ± 34 ng/ml). Quantititative in situ hybridization histochemistry revealed that corticotrophin-releasing factor mRNA levels in the medial parvocellular part of the hypothalamic paraventricular nucleus were significantly lower in MSG-treated rats. MSG lesioning resulted in an enhanced response of corticosterone to restraint stress (1309 ± 92 ng/ml compared with 628 ± 125 ng/ml in sham-lesioned animals), while ACTH responses to restraint stress in MSG-lesioned and sham-MSG groups were not significantly different (160 ± 24 pg/ml and 167 ± 24 pg/ml respectively). These data suggest that MSG-lesioned rats have an increased adrenocortical sensitivity. In rats subjected to the chronic osmotic stimulus of drinking 2% saline for 12 days, plasma ACTH levels were significantly reduced (15 ± 5 pg/ml) and the ACTH and corticosterone responses to restraint stress were eliminated. ACTH levels were also reduced in MSG-treated animals given 2% saline and the ACTH response to acute stress remained absent in these animals. However, a robust corticosterone response to restraint stress was observed in saline-treated MSG-lesioned rats. These data demonstrate that MSG lesioning results in elevated basal and stress-induced plasma corticosterone, and restores the adrenocortical response to stress which is absent in chronically osmotically stimulated rats. The evidence is consistent with the suggestion that MSG lesions a pathway involved in tonic inhibition of the HPA axis. In addition, the adrenocortical sensitivity to ACTH and other secretagogues may be increased in MSG-treated animals. Journal of Endocrinology (1994) 141, 497–503

Download Full-text

Effect of vasopressin 1b receptor blockade on the hypothalamic–pituitary–adrenal response of chronically stressed rats to a heterotypic stressor

Journal of Endocrinology ◽

10.1677/joe-08-0425 ◽

2008 ◽

Vol 200 (3) ◽

pp. 285-291 ◽

Cited By ~ 22

Author(s):

Francesca Spiga ◽

Louise R Harrison ◽

Cliona P MacSweeney ◽

Fiona J Thomson ◽

Mark Craighead ◽

...

Keyword(s):

White Noise ◽

Chronic Stress ◽

Hpa Axis ◽

Home Cage ◽

Male Rats ◽

Receptor Blockade ◽

Hypothalamic Pituitary Adrenal ◽

Corticosterone Secretion ◽

Corticosterone Response ◽

Adrenal Response

Exposure to chronic restraint (CR) modifies the hypothalamic–pituitary–adrenal (HPA) axis response to subsequent acute stressors with adaptation of the response to a homotypic and sensitization of the response to a heterotypic stressor. Since vasopressin (AVP) activity has been reported to change during chronic stress, we investigated whether this was an important factor in HPA facilitation. We therefore tested whether vasopressin 1b receptor (AVPR1B) blockade altered the ACTH and corticosterone response to heterotypic stressors following CR stress. Adult male rats were exposed to CR, single restraint, or were left undisturbed in the home cage. Twenty-four hours after the last restraint, rats were injected with either a AVPR1B antagonist (Org, 30 mg/kg, s.c.) or vehicle (5% mulgofen in saline, 0.2/kg, s.c.) and then exposed to either restraint, lipopolysaccharide (LPS) or white noise. CR resulted in the adaptation of the ACTH and corticosterone response to restraint and this effect was not prevented by pretreatment with Org. Although we found no effect of CR on LPS-induced ACTH and corticosterone secretion, both repeated and single episodes of restraint induced the sensitization of the ACTH, but not corticosterone response to acute noise. Pretreatment with Org reduced the exaggerated ACTH response to noise after both single and repeated exposure to restraint.

Download Full-text