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 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 Liver-Selective Transgene Rescue of Hypothalamic-Pituitary-Adrenal Axis Dysfunction in 11β-Hydroxysteroid Dehydrogenase Type 1-Deficient Mice

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 961-966 ◽  
Author(s):  
Janice M. Paterson ◽  
Megan C. Holmes ◽  
Christopher J. Kenyon ◽  
Roderick Carter ◽  
John J. Mullins ◽  
...  
Keyword(s):  
Hydroxysteroid Dehydrogenase ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Deficient Mice ◽  
Pituitary Adrenal Axis

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.

Activation of the Hypothalamic- Pituitary-Adrenal Axis in IL-1β-Converting Enzyme-Deficient Mice

2000 ◽  
Vol 7 (4) ◽  
pp. 189-194 ◽  
Author(s):  
Stéphane Liège ◽  
Elisabeth Moze ◽  
Keith W. Kelley ◽  
Patricia Parnet ◽  
Pierre J. Neveu
Keyword(s):  
Hypothalamic Pituitary Adrenal Axis ◽  
Converting Enzyme ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Enzyme Deficient ◽  
Deficient Mice ◽  
Pituitary Adrenal Axis
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