Decreased Corticotropin‐Releasing Factor Receptor Expression and Adrenocorticotropic Hormone Responsiveness in Anterior Pituitary Cells of Wistar‐Kyoto Rats

Hauger, Richard L.; Shelat, Suresh G.; Redei, Eva E.

doi:10.1046/j.0007-1331.2001.00752.x

Cited by 18 publications

(8 citation statements)

References 58 publications

(92 reference statements)

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“…Animal models utilizing invasive techniques that can rarely be implemented in human subjects are often used in this confirmatory manner. For example, a recent rodent study confirmed the hypothesis that diminished CRF receptor binding in the anterior pituitary is associated with a blunted ACTH response to CRF stimulation (Hauger et al, 2002). Preclinical data is certainly informative; however, its utility is limited by the incomplete homology of any animal model for the human condition (Newport et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Corticotropin-Releasing Factor (CRF) and Vasopressin Concentrations Predict Pituitary Response in the CRF Stimulation Test: A Multiple Regression Analysis

Newport

Heim

Owens

et al. 2002

Neuropsychopharmacol

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There is considerable evidence that stress-related psychiatric disorders, including depression and post-traumatic stress disorder (PTSD), are associated with hypersecretion of corticotropin-releasing factor (CRF) within the central nervous system (CNS). One line of evidence that is consistent with central CRF hypersecretion in these disorders is the blunted adrenocorticotropin hormone (ACTH) response to intravenous CRF administration, likely a consequence, at least in part, of downregulation of anterior pituitary CRF receptors. The present study tests the hypothesis that elevated cerebrospinal fluid (CSF) concentrations of CRF and a secondary ACTH secretagogue, arginine vasopressin (AVP), are associated with diminished adenohypophyseal responses in a standard CRF stimulation test. CSF concentrations of CRF and AVP, and plasma ACTH responses to the administration of 1 mg/kg ovine CRF (oCRF) were measured in healthy adult women with and without current major depression and/or a history of significant childhood abuse. The primary outcome measure was ACTH area under the curve (AUC) in the CRF stimulation test. Multiple linear regression was performed to identify the impact of CSF CRF and AVP concentrations upon the pituitary response to CRF stimulation. The regression model explained 56.5% of the variation in the ACTH response to CRF stimulation. The relationship of CSF concentrations of CRF to ACTH responses to CRF were best described by a third-order function that was inversely correlated over most of the range of studied values. The association of ACTH response with CSF concentration of AVP and the dose of oCRF followed second-order kinetics. These findings support the hypothesis that central CRF hypersecretion is associated with a blunted ACTH response to exogenously administered CRF, explaining almost 60% of the variation in the ACTH response to CRF.

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Corticotropin-Releasing Factor (CRF) and Vasopressin Concentrations Predict Pituitary Response in the CRF Stimulation Test: A Multiple Regression Analysis

Newport

Heim

Owens

et al. 2002

Neuropsychopharmacol

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“…Repeated or prolonged stimulation with CRH reduces CRH receptor binding and can cause reduced ACTH responsiveness or desensitization [31]. Indeed chronically activated corticotrophs generally show blunted ACTH response to CRH [32]. To test the hypothesis that IS exposure decreases the responsiveness of the anterior pituitary to CRH, quartered anterior pituitaries were assessed for their ability to release ACTH in response to in vitro CRH stimulation.…”

Section: Resultsmentioning

confidence: 99%

Stress-Induced Sensitization of the Hypothalamic-Pituitary Adrenal Axis Is Associated with Alterations of Hypothalamic and Pituitary Gene Expression

et al. 2004

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We have previously reported that inescapable tail shock (IS) produces persistent changes in hypothalamic-pituitary-adrenal (HPA) axis function. These changes are manifest as an elevation in basal corticosterone (CORT) levels, a sensitization of adrenocorticotropin hormone (ACTH) and CORT responses to subsequent challenge, and a failure of dexamethasone to suppress both the ACTH and CORT responses to a subsequent challenge. The experiments presented here examine IS-induced alterations in the responsiveness of the HPA axis, particularly at the level of the anterior pituitary. The data presented show that adrenalectomy does not abolish the IS-induced sensitization of the HPA axis, suggesting that the sensitization is not solely caused by a defect in glucocorticoid negative feedback. Analysis of gene expression in the anterior pituitary revealed that IS exposure persistently elevated basal levels of proopiomelanocortin (POMC; the precursor to ACTH) mRNA and sensitized the POMC hnRNA and c-fos mRNA response to a subsequent challenge. Analysis of gene expression in the parvocellular division of the paraventricular nucleus of the hypothalamus (pPVN) after IS exposure revealed that basal levels of corticotropin-releasing hormone (CRH) mature mRNA are elevated and the c-fos mRNA response to a subsequent challenge is enhanced. Finally, a blunted in vitro ACTH response to CRH challenge is observed after IS exposure. These data suggest that the ultimate source of the IS-induced sensitization is not the anterior pituitary and implicate an increased drive on the anterior pituitary from the pPVN.

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“…A blunted ACTH response to CRH has consistently been found in adult patients with severe melancholic major depressive ill-ness~Gold, Holsboer et al, 1984!. The ACTH response may be blunted because of downregulation of pituitary CRH receptors in response to chronically increased hypothalamic CRH secretioñ Hauger et al, 2002;Newport et al, 2003! and0or loss of fast-feedback regulation in the hypothalamus and hippocampus~Young, Haskett, Murphy-Weinberg, Watson, & Akil, 1991!. A normal cortisol response to blunted ACTH secretion is evidence of a hyperresponsive adrenal cortex, reflecting a disruption in the homeostasis of the HPA axis~Gold et al, 1995!. Because these children were not hypercortisolemic at baseline, it is likely that they are in a state of relatively mild hypersecretion of hypothalamic CRH.…”

Section: Offspring Diagnosismentioning

confidence: 99%

Maternal and environmental factors influence the hypothalamic–pituitary–adrenal axis response to corticotropin-releasing hormone infusion in offspring of mothers with or without mood disorders

Ronsaville¹,

Municchi²,

Laney³

et al. 2006

Develop. Psychopathol.

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Individuals with melancholic major depression exhibit basal hypercortisolism and an attenuated ACTH response to exogenous corticotropin-releasing hormone (CRH) infusion. Given the greater incidence of depression in children of depressed parents, we examined the ACTH and cortisol responses to ovine CRH (oCRH) infusion in 63 adolescent offspring of mothers with major depression, bipolar illness, or no psychiatric illness. Psychiatric and observational assessments of these families had been conducted over the course of 10 years preceding this study. We examined the children's responses to CRH in relation to maternal characteristics and family environment and found the following: (a) cortisol responses were negatively related to chronic family stress and (b) offspring of depressed mothers with an avoidant personality disorder showed an exaggerated ACTH response. In addition, adolescents in late puberty (Tanner 4 and 5) had lower ACTH and cortisol responses to oCRH infusion than those in early puberty. Further, offspring with early histories of mood problems, and those who developed major depressive disorder as young adults, did not exhibit basal hypercortisolism but did show an attenuated ACTH response to CRH. Our results add to the growing body of literature showing the influence of maternal characteristics and environmental factors on hypothalamic-pituitary-adrenal axis patterns in children.

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Decreased Corticotropin‐Releasing Factor Receptor Expression and Adrenocorticotropic Hormone Responsiveness in Anterior Pituitary Cells of Wistar‐Kyoto Rats

Cited by 18 publications

References 58 publications

Cerebrospinal Fluid Corticotropin-Releasing Factor (CRF) and Vasopressin Concentrations Predict Pituitary Response in the CRF Stimulation Test: A Multiple Regression Analysis

Cerebrospinal Fluid Corticotropin-Releasing Factor (CRF) and Vasopressin Concentrations Predict Pituitary Response in the CRF Stimulation Test: A Multiple Regression Analysis

Stress-Induced Sensitization of the Hypothalamic-Pituitary Adrenal Axis Is Associated with Alterations of Hypothalamic and Pituitary Gene Expression

Maternal and environmental factors influence the hypothalamic–pituitary–adrenal axis response to corticotropin-releasing hormone infusion in offspring of mothers with or without mood disorders

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