scholarly journals 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

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3587-3592 ◽  
Author(s):  
Young Taek Oh ◽  
Ki-Sook Oh ◽  
Insug Kang ◽  
Jang H. Youn
Keyword(s):  
Plasma Glucose ◽  
Plasma Corticosterone ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
Plasma Acth ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Adenosine Receptor Agonist ◽  
Plasma Ffa ◽  
The Brain ◽  
Pituitary Adrenal Axis

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.

scholarly journals Lipopolysaccharide has selective actions on sub-populations of catecholaminergic neurons involved in activation of the hypothalamic–pituitary–adrenal axis and inhibition of prolactin secretion

2005 ◽  
Vol 184 (2) ◽  
pp. 393-406 ◽  
Author(s):  
Jacob H Hollis ◽  
Stafford L Lightman ◽  
Christopher A Lowry
Keyword(s):  
Immune Activation ◽  
Plasma Corticosterone ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
Plasma Prolactin ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Neuroendocrine Function ◽  
Cell Groups ◽  
Neuroendocrine Responses ◽  
Pituitary Adrenal Axis

Immune activation results in adaptive neuroendocrine responses, including activation of the hypothalamic–pituitary–adrenal axis, which are dependent on the integrity of medullary catecholaminergic (CA) systems. In contrast, although specific roles of pontine, midbrain, and hypothalamic CA systems in neuroendocrine function have been described, the functional roles of these CA systems in modulating neuroendocrine function during immune responses have not been investigated. We have, therefore, investigated the effects of immune activation on the various CA systems of the central nervous system (CNS) and explored this relationship with changes in plasma corticosterone and plasma prolactin. Male BALB/c mice were injected with lipopolysaccharide (LPS, 500 μg/kg i.p.) and 2 h later cardiac blood was taken and mice were perfused with fixative. Immunostaining procedures were performed using antibodies raised against c-Fos and tyrosine hydroxylase, a marker of CA neurons, and detailed topographical analysis of the CA systems within the CNS was performed. LPS-injected mice had increased concentrations of plasma corticosterone and decreased concentrations of plasma prolactin compared with vehicle-injected controls. LPS-injected mice had increased numbers of c-Fos-positive CA neurons within the medullary (A1, A2, C1, C2), pontine (A6) and midbrain (A10) cell groups when compared with vehicle-injected controls. Among hypothalamic CA cell groups, LPS had differential effects on the numbers of c-Fos-positive CA neurons in topographically organised subdivisions of the arcuate nucleus (A12). Changes in plasma prolactin concentrations correlated with the numbers of c-Fos-positive CA neurons within the area postrema, the medullary CA cell groups, the medial posterior division of the arcuate, and the zona incerta. The present study identifies topographically organised, anatomically distinct CA systems that are likely to modulate some of the neuroendocrine responses to immune activation, and may provide novel targets for the relief of symptoms associated with illness and disease.

Regulation of the hypothalamic–pituitary–adrenal axis in birth

1988 ◽  
Vol 66 (8) ◽  
pp. 1106-1112 ◽  
Author(s):  
A. N. Brooks ◽  
J. R. G. Challis
Keyword(s):  
Fetal Brain ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
Adrenal Function ◽  
Pituitary Cells ◽  
Plasma Acth ◽  
Fetal Sheep ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Pituitary Adrenal Axis

In sheep an increase in fetal pituitary–adrenal function, reflected in rising concentrations of plasma ACTH and cortisol, is important in relation to fetal organ maturation and the onset of parturition. This review presents evidence that implicates the hypothalamic–pituitary–adrenal axis in the control of parturition and describes recent experiments that explore in detail the maturation of the fetal hypothalamus and pituitary in relation to fetal adrenal function. Recent improvements for the measurement of ACTH in unextracted plasma and the ability to maintain vascular catheters in chronically catheterized fetal sheep have enabled subtle changes in fetal ACTH concentrations to be detected. As a result of these advances it has now been established that the terminal rise in cortisol, which is responsible for the onset of parturition in sheep, is preceded by an increase in fetal plasma ACTH concentrations. This has led to the hypothesis that birth results from the sequential development of the fetal hypothalamic–pituitary–adrenal axis with the signal originating from the fetal brain. This increase in trophic drive to the fetal adrenal may result from changes in the responsiveness of the fetal pituitary gland to factors that stimulate the release of ACTH. Corticotropin releasing factor (CRF) and arginine vasopressin are two such factors that stimulate the secretion of ACTH and cortisol secretion in the chronically catheterized fetal sheep. The response to these factors increases with gestational age and is sensitive to glucocorticoid feedback. Furthermore, repeated administration of CRF to immature fetal sheep results in pituitary and adrenal activation and in some cases may lead to premature parturition. Until recently, little was known of the controls of CRF secretion from the fetal hypothalamus. However, CRF has now been detected in the fetal sheep hypothalamus by radioimmunoassay and with immunohistochemistry, during the last third of pregnancy. The CRF material detected by radioimmunoassay co-elutes with synthetic ovine CRF on Sephadex G75 chromatography and also stimulates the release of ACTH from adult sheep pituitary cells maintained in culture. Furthermore at d100 of pregnancy (term of 145 days), CRF is released from fetal sheep hypothalami perifused in vitro both under basal conditions and in response to potassium-induced nerve terminal depolarization. Dexamethasone does not affect the release of CRF under these conditions. At d140, the hypothalamus contains similar quantities of immunoreactive and bioactive CRF which are released at a higher rate during in vitro perifusion. Potassium causes a similar release of CRF compared with d100 and again is unaffected by the presence of dexamethasone. However, at d140, dexamethasone does reduce basal CRF release. These results provide evidence for maturation of glucocorticoid feedback mechanisms at the level of the fetal hypothalamus and, together with the additional data presented in this review, illustrate the complexity of neuroendocrine control of the hypothalamic–pituitary–adrenal axis in birth.

Actions of neuropeptide W in paraventricular hypothalamus: implications for the control of stress hormone secretion

2005 ◽  
Vol 288 (1) ◽  
pp. R270-R275 ◽  
Author(s):  
Meghan M. Taylor ◽  
Erik A. Yuill ◽  
Jennifer R. Baker ◽  
Catharine C. Ferri ◽  
Alastair V. Ferguson ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Peripheral Circulation ◽  
Plasma Corticosterone ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
Neuroendocrine Cells ◽  
Male Rats ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Relevant Role ◽  
Pituitary Adrenal Axis

Neuropeptide W (NPW) is produced in neurons located in hypothalamus and brain stem, and its receptors are present in the hypothalamus, in particular in the paraventricular nucleus (PVN). Intracerebroventricular (ICV) administration of NPW activated, in a dose-related fashion, the hypothalamic-pituitary-adrenal axis, as determined by plasma corticosterone levels in conscious rats but, at those same doses, did not stimulate the release of oxytocin or vasopressin into the peripheral circulation or alter blood pressure or heart rate. The ability of ICV-administered NPW to stimulate the hypothalamic-pituitary-adrenal axis in conscious male rats was blocked by intravenous pretreatment with a corticotropin-releasing hormone antagonist. This suggested an action of NPW in the parvocellular division of the PVN. Indeed, in hypothalamic slice preparations (whole cell patch recording), bath application of NPW depolarized and increased the spike frequency of the majority of electrophysiologically identified putative neuroendocrine PVN neurons. Effects on membrane potential were maintained in the presence of TTX, suggesting them to be direct postsynaptic actions on these neuroendocrine cells. Our data suggest that endogenous NPW, produced in brain, may play a physiologically relevant role in the neuroendocrine response to stress.

scholarly journals Intracellular Regeneration of Glucocorticoids by 11β-Hydroxysteroid Dehydrogenase (11β-HSD)-1 Plays a Key Role in Regulation of the Hypothalamic-Pituitary-Adrenal Axis: Analysis of 11β-HSD-1-Deficient Mice**The Wellcome Trust supported this work through a program grant (to J.J.M. and J.R.S.) and a Career Development Fellowship (to M.C.H.).

Endocrinology ◽  
2001 ◽  
Vol 142 (1) ◽  
pp. 114-120 ◽  
Author(s):  
Hayley J. Harris ◽  
Yuri Kotelevtsev ◽  
John J. Mullins ◽  
Jonathan R. Seckl ◽  
Megan C. Holmes
Keyword(s):  
Plasma Corticosterone ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
Messenger Rnas ◽  
Intracellular Regeneration ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Important Regulator ◽  
Deficient Mice ◽  
Pituitary Adrenal Axis

Abstract 11β-Hydroxysteroid dehydrogenases (11β-HSDs) catalyze interconversion of active corticosterone and inert 11-dehydrocorticosterone, thus regulating glucocorticoid access to intracellular receptors in vivo. 11β-HSD type 1 is a reductase, locally regenerating active glucocorticoids. To explore the role of this isozyme in the brain, we examined hypothalamic-pituitary-adrenal axis (HPA) regulation in mice homozygous for a targeted disruption of the 11β-HSD-1 gene. 11β-HSD-1-deficient mice showed elevated plasma corticosterone and ACTH levels at the diurnal nadir, with a prolonged corticosterone peak, suggesting abnormal HPA control and enhanced circadian HPA drive. Despite elevated corticosterone levels, several hippocampal and hypothalamic glucocorticoid-sensitive messenger RNAs were normally expressed in 11β-HSD-1-deficient mice, implying reduced effective glucocorticoid activity within neurons. 11β-HSD-1-deficient mice showed exaggerated ACTH and corticosterone responses to restraint stress, with a delayed fall after stress, suggesting diminished glucocorticoid feedback. Indeed, 11β-HSD-1-deficient mice were less sensitive to exogenous cortisol suppression of HPA activation. Thus 11β-HSD-1 amplifies glucocorticoid feedback on the HPA axis and is an important regulator of neuronal glucocorticoid exposure under both basal and stress conditions in vivo.

scholarly journals The Hypothalamic-Pituitary-Adrenal Axis Response to Stress in Mice Lacking Functional Vasopressin V1b Receptors

Endocrinology ◽  
2007 ◽  
Vol 148 (2) ◽  
pp. 849-856 ◽  
Author(s):  
Stephen J. Lolait ◽  
Lesley Q. Stewart ◽  
David S. Jessop ◽  
W. Scott Young ◽  
Anne-Marie O’Carroll
Keyword(s):  
Chronic Stress ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
Wild Type ◽  
Plasma Acth ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Significant Difference ◽  
Response To Stress ◽  
Pituitary Adrenal Axis

The role of arginine vasopressin (Avp) as an ACTH secretagogue is mediated by the Avp 1b receptor (Avpr1b) found on anterior pituitary corticotropes. Avp also potentiates the actions of CRH (Crh) and appears to be an important mediator of the hypothalamic-pituitary-adrenal axis response to chronic stress. To investigate the role of Avp in the hypothalamic-pituitary-adrenal axis response to stress, we measured plasma ACTH and corticosterone (CORT) levels in Avpr1b knockout (KO) mice and wild-type controls in response to two acute (restraint and insulin administration) and one form of chronic (daily restraint for 14 d) stress. No significant difference was found in the basal plasma levels of ACTH and CORT between the two genotypes. Acute restraint (30 min) increased plasma ACTH and CORT to a similar level in both the Avpr1b mutant and wild-type mice. In contrast, plasma ACTH and CORT levels induced by hypoglycemia were significantly decreased in the Avpr1b KO mice when compared with wild-type littermates. There was no difference in the ACTH response to acute and chronic restraint in wild-type mice. In the Avpr1b KO group subjected to 14 sessions of daily restraint, plasma ACTH was decreased when compared with wild-type mice. On the other hand, the CORT elevations induced by restraint did not adapt in the Avpr1b KO or wild-type mice. The data suggest that the Avpr1b is required for the normal pituitary and adrenal response to some acute stressful stimuli and is necessary only for a normal ACTH response during chronic stress.

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