Neuroregulation of the Hypothalamus-Pituitary-Adrenal (HPA) Axis in Humans: Effects of GABA-, Mineralocorticoid-, and GH-Secretagogue-Receptor Modulation

The hypothalamus-pituitary-adrenal (HPA) axis exerts a variety of effects at both the central and peripheral level. Its activity is mainly regulated by CRH, AVP, and the glucocorticoid-mediated feedback action. Moreover, many neurotransmitters and neuropeptides influence HPA axis activity by acting...

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Main Authors: Roberta Giordano, Micaela Pellegrino, Andreea Picu, Lorenza Bonelli, Marcella Balbo, Rita Berardelli, Fabio Lanfranco, Ezio Ghigo
Format: Article
Language:English
Published: Wiley 2006-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1100/tsw.2006.09
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author Roberta Giordano
Micaela Pellegrino
Andreea Picu
Lorenza Bonelli
Marcella Balbo
Rita Berardelli
Fabio Lanfranco
Ezio Ghigo
author_facet Roberta Giordano
Micaela Pellegrino
Andreea Picu
Lorenza Bonelli
Marcella Balbo
Rita Berardelli
Fabio Lanfranco
Ezio Ghigo
author_sort Roberta Giordano
collection DOAJ
description The hypothalamus-pituitary-adrenal (HPA) axis exerts a variety of effects at both the central and peripheral level. Its activity is mainly regulated by CRH, AVP, and the glucocorticoid-mediated feedback action. Moreover, many neurotransmitters and neuropeptides influence HPA axis activity by acting at the hypothalamic and/or suprahypothalamic level. Among them, GABA and Growth Hormone Secretagogues (GHS)/GHS-receptor systems have been shown to exert a clear inhibitory and stimulatory effect, respectively, on corticotroph secretion. Alprazolam (ALP), a GABA-A receptor agonist, shows the most marked inhibitory effect on both spontaneous and stimulated HPA axis activity, in agreement with its peculiar efficacy in panic disorders and depression where an HPA axis hyperactivation is generally present. Ghrelin and synthetic GHS possess a marked ACTH/cortisol-releasing effect in humans and the ghrelin/GHS-R system is probably involved in the modulation of the HPA response to stress and nutritional/metabolic variations. The glucocorticoid-mediated negative feedback action is mediated by both glucocorticoid (GR) and mineralocorticoid (MR) receptors activation at the central level, mainly in the hippocampus. In agreement with animal studies, MRs seem to play a crucial role in the maintenance of the circadian ACTH and cortisol rhythm, through the modulation of CRH and AVP release. GABA agonists (mainly ALP), ghrelin, as well as MR agonists/antagonists, may represent good tools to explore the activity of the HPA axis in both physiological conditions and pathological states characterized by an impaired control of the corticotroph function.
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spelling doaj-art-78e0006dee6f4a4c9ec38f5fc65854f52025-08-20T03:35:23ZengWileyThe Scientific World Journal1537-744X2006-01-01611110.1100/tsw.2006.09Neuroregulation of the Hypothalamus-Pituitary-Adrenal (HPA) Axis in Humans: Effects of GABA-, Mineralocorticoid-, and GH-Secretagogue-Receptor ModulationRoberta Giordano0Micaela Pellegrino1Andreea Picu2Lorenza Bonelli3Marcella Balbo4Rita Berardelli5Fabio Lanfranco6Ezio Ghigo7Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, ItalyDivision of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, ItalyDivision of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, ItalyDivision of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, ItalyDivision of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, ItalyDivision of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, ItalyDivision of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, ItalyDivision of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, ItalyThe hypothalamus-pituitary-adrenal (HPA) axis exerts a variety of effects at both the central and peripheral level. Its activity is mainly regulated by CRH, AVP, and the glucocorticoid-mediated feedback action. Moreover, many neurotransmitters and neuropeptides influence HPA axis activity by acting at the hypothalamic and/or suprahypothalamic level. Among them, GABA and Growth Hormone Secretagogues (GHS)/GHS-receptor systems have been shown to exert a clear inhibitory and stimulatory effect, respectively, on corticotroph secretion. Alprazolam (ALP), a GABA-A receptor agonist, shows the most marked inhibitory effect on both spontaneous and stimulated HPA axis activity, in agreement with its peculiar efficacy in panic disorders and depression where an HPA axis hyperactivation is generally present. Ghrelin and synthetic GHS possess a marked ACTH/cortisol-releasing effect in humans and the ghrelin/GHS-R system is probably involved in the modulation of the HPA response to stress and nutritional/metabolic variations. The glucocorticoid-mediated negative feedback action is mediated by both glucocorticoid (GR) and mineralocorticoid (MR) receptors activation at the central level, mainly in the hippocampus. In agreement with animal studies, MRs seem to play a crucial role in the maintenance of the circadian ACTH and cortisol rhythm, through the modulation of CRH and AVP release. GABA agonists (mainly ALP), ghrelin, as well as MR agonists/antagonists, may represent good tools to explore the activity of the HPA axis in both physiological conditions and pathological states characterized by an impaired control of the corticotroph function.http://dx.doi.org/10.1100/tsw.2006.09
spellingShingle Roberta Giordano
Micaela Pellegrino
Andreea Picu
Lorenza Bonelli
Marcella Balbo
Rita Berardelli
Fabio Lanfranco
Ezio Ghigo
Neuroregulation of the Hypothalamus-Pituitary-Adrenal (HPA) Axis in Humans: Effects of GABA-, Mineralocorticoid-, and GH-Secretagogue-Receptor Modulation
The Scientific World Journal
title Neuroregulation of the Hypothalamus-Pituitary-Adrenal (HPA) Axis in Humans: Effects of GABA-, Mineralocorticoid-, and GH-Secretagogue-Receptor Modulation
title_full Neuroregulation of the Hypothalamus-Pituitary-Adrenal (HPA) Axis in Humans: Effects of GABA-, Mineralocorticoid-, and GH-Secretagogue-Receptor Modulation
title_fullStr Neuroregulation of the Hypothalamus-Pituitary-Adrenal (HPA) Axis in Humans: Effects of GABA-, Mineralocorticoid-, and GH-Secretagogue-Receptor Modulation
title_full_unstemmed Neuroregulation of the Hypothalamus-Pituitary-Adrenal (HPA) Axis in Humans: Effects of GABA-, Mineralocorticoid-, and GH-Secretagogue-Receptor Modulation
title_short Neuroregulation of the Hypothalamus-Pituitary-Adrenal (HPA) Axis in Humans: Effects of GABA-, Mineralocorticoid-, and GH-Secretagogue-Receptor Modulation
title_sort neuroregulation of the hypothalamus pituitary adrenal hpa axis in humans effects of gaba mineralocorticoid and gh secretagogue receptor modulation
url http://dx.doi.org/10.1100/tsw.2006.09
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