The Hypothalamic‐Pituitary‐Adrenal Axis in Obesity

Chalew, Stuart A.; Nagel, Heinz; Shore, Shirah

doi:10.1002/j.1550-8528.1995.tb00163.x

Cited by 48 publications

(39 citation statements)

References 113 publications

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“…This difference between the sexes is not an unexpected ®nding, since there is evidence that females may have a greater sensitivity in the adrenals to different stimulatory neuropeptides, including ACTH. 10,11,18,19 The lack of correlation between the activity of the HPA axis and anthropometric indices of body fat distribution, contrary to what was previously reported in women, 3,5 may be explained by the fact that obesity in males is almost always associated with a parallel increase of abdominal and visceral fat, which means that the central distribution of body fat depends on the actual presence of obesity in males. This is exempli®ed by the very high correlation coef®cients between BMI and FM and waist circumference (in this study: r 0.97, P`0.0001, and r 0.89, P`0.0001, respectively) but not with the hip circumference (NS), which is commonly found in a male population.…”

Section: Discussionmentioning

confidence: 70%

ACTH and cortisol response to combined corticotropin releasing hormone-arginine vasopressin stimulation in obese males and its relationship to body weight, fat distribution and parameters of the metabolic syndrome

et al. 1999

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OBJECTIVES: To investigate the activity of the hypothalamic ± pituitary ± adrenal (HPA) axis in male obesity and its relationship with several prominent parameters of the metabolic syndrome. DESIGN: A cross-sectional clinical study of the activity of the HPA axis in groups of obese males and normal-weight controls. SUBJECTS: Seventeen obese non-diabetic males with a body mass index (BMI) b 28 and eight normal-weight controls were examined. MEASUREMENTS: Fat free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance, and the waistto-hip circumference ratio (WHR) was calculated in all subjects. Baseline samples were taken for sex hormone and lipid determination, and an oral glucose tolerance test (OGTT) was performed for glucose and insulin determination. The activity of the HPA axis was determined by the combined administration of human corticotropin releasing hormone (CRH) (100 m mg) and arginine vasopressin (AVP) (0.3 IU). RESULTS: As expected, FFM and FM and the WHR were higher in obese men than in controls, as were fasting insulin and stimulated (as area under the curve (AUC)) glucose and insulin concentrations. Baseline adrenocorticotropin (ACTH) and cortisol concentrations were similar in both groups, but stimulated (as AUC), ACTH was higher (P`0.05) in obese subjects than in controls, whereas no signi®cant difference in cortisol AUC was present. Since the main differences between obese subjects and controls were present during the early 30 min of the test, the correlation coef®cients between total and incremental ACTH AUC 0 ± 30 min and cortisol AUC 0 ± 30 min and all other variables were analyzed. A signi®cant correlation coef®cient was present between them and all anthropometric parameters, fasting insulin and insulin AUC , but not with androgens and gonadotrophins. In addition, a signi®cant correlation was present between total and incremental ACTH AUC 0 ± 30 min and triglyceride concentrations. However, after adjusting for BMI or FM values, all correlation coef®cients became non-signi®cant, except the one between incremental ACTH AUC 0 ± 30 min and insulin AUC (P`0.05). CONCLUSION: These ®ndings indicate that obese men may also have an altered pituitary response to combined CRHaAVP stimulation, which appears to be predominantly related to body size and total body fat. ACTH hyperresponsiveness after CRHaAVP stimulation also appears to be related to hyperinsulinaemia, but underlying mechanisms of this relationship remain to be elucidated.

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Section: Discussionmentioning

confidence: 70%

ACTH and cortisol response to combined corticotropin releasing hormone-arginine vasopressin stimulation in obese males and its relationship to body weight, fat distribution and parameters of the metabolic syndrome

et al. 1999

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“…However, it has to be mentioned that the downregulating effect of leptin on CRH mRNA in the PVH was seen in CRH-containing neurons, which primarily control the pituitary-adrenal axis activity and perhaps not extensively the energy balance [35, 36]. Consistent with this claim is a previous report showing the inability of a PVH lesion to prevent the effects of corticosterone on energy balance from occurring [37].…”

Section: Discussionmentioning

confidence: 72%

Effects of Leptin and Corticosterone on the Expression of Corticotropin-Releasing Hormone, Agouti-Related Protein, and Proopiomelanocortin in the Brain of <i>ob/ob</i> Mouse

2001

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The present study was conducted to assess the effect of leptin and corticosterone on the expression of corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC) and agouti-related protein (AGRP) in the mouse brain. To this end, a 3 × 3 factorial experiment was designed in which adrenalectomized (ADX) ob/ob mice were treated with leptin and corticosterone. Leptin and corticosterone downregulated CRH expression in the paraventricular hypothalamic nucleus (PVH). Leptin prevented the stimulating effects of ADX on the expression of CRH and the combination of small doses of leptin and corticosterone was as potent as the high dose of corticosterone in suppressing CRH mRNA expression in the PVH. Leptin and corticosterone enhanced the expression of CRH in the central nucleus of amygdala and in the bed nucleus of the stria terminalis. In addition, the present results confirmed the downregulating effects of leptin on the expression of AGRP mRNA in the hypothalamic arcuate nucleus (ARC), and demonstrated that this effect was more apparent in ADX mice treated with corticosterone than in ADX mice not supplemented with corticosterone. Also, leptin and corticosterone had opposite effects on the expression of POMC in the ARC. The opposite effect of leptin and corticosterone on the expression of POMC and AGRP seems consistent with the reported effects that these hormones and peptides have on food intake and thermogenesis, suggesting that the modulation of POMC and AGRP expression can be a mechanism whereby leptin and corticosterone exert their effects in the regulation of energy balance. In contrast, the similarity in the action of leptin and corticosterone is not a priori consistent with a role of CRH in the effects of these hormones in the regulation of energy balance. The downregulating effect of leptin on the expression of CRH in the PVH strongly suggests that leptin can be a potent regulator of hypothalamic-pituitary-adrenal axis activity. Finally, the present results suggest that the effects of leptin on the expression of CRH, POMC and AGRP are not curbed by glucocorticoids.

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“…However, this test does not make it possible to discriminate between obese and nonobese subjects, the suppression of the HPA activity being provided by 1 mg-dexamethasone maximal or near-maximal (27). Therefore, this test may not reflect subtle changes in central feedback regulation.…”

Section: Discussionmentioning

confidence: 99%

Cortisol and ACTH Response to Oral Dexamethasone in Obesity and Effects of Sex, Body Fat Distribution, and Dexamethasone Concentrations: A Dose-Response Study

Pasquali

Ambrosi

Armanini

et al. 2002

The Journal of Clinical Endocrinology & Metabolism

107

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There is increasing evidence that the abdominal obesity phenotype may be associated with multiple alterations of the hypothalamic-pituitary-adrenocortical (HPA) axis activity in both sexes. Our hypothesis is that the lack of adequate cortisol suppression after the dexamethasone test may constitute an indirect marker of HPA axis hyperactivity in the presence of the abdominal obesity phenotype. A total of 34 normal-weight (13 men and 21 women) and 87 obese (36 men and 51 women), healthy, nondepressed subjects therefore underwent four different dexamethasone suppression tests randomly performed at varying intervals of at least 1 wk between each test. After a standard overnight 1-mg dexamethasone test, which served as a reference, three other tests were randomly performed at 1-wk intervals by administering 0.0035, 0.0070, and 0.015 mg oral dexamethasone per kilogram of body weight overnight. Blood samples were obtained for cortisol, ACTH, and dexamethasone. Results were analyzed separately in men and women as well as in normal-weight [body mass index (BMI) <25 kg/m 2 ] and overweight or obese (BMI >25 kg/m 2 ) subjects. The waist circumference and the waist to hip ratio (WHR) were used as markers of body fat distribution. After the standard 1-mg test, cortisol suppression was greater than 90% in all subjects. However, after each test, obese women had significantly higher values of percent cortisol and percent ACTH suppression than normal-weight women without any difference between obese and normal-weight men. Considering the response to the three variable-dose tests, a clear doseresponse pattern (P < 0.001 for trend analysis) in percent cortisol and percent ACTH suppression was found in all subjects. After each test men had significantly higher dexamethasone levels than women, regardless of BMI. However, obese women, but not men, had significantly higher dexamethasone levels after each test than their normal-weight counterpart. Plasma dexamethasone concentrations were dose related (P < 0.001 for trend analysis) in all subjects, but the doserelated increase was significantly higher in normal-weight men than normal-weight women, whereas it was similar in obese subjects of both sexes. Stepwise multiple regression analysis revealed that both percent cortisol and percent ACTH variations were significantly and negatively influenced by dexamethasone levels, as well as by waist circumference values in men, and independently by BMI and waist circumference in women. However, in contrast to what has been found in men, a divergent contribution of BMI and waist circumference was found in women indicating that, with increasing waist values, a smaller suppression of the HPA axis was found with respect to that expected on the basis of BMI values. In conclusion, this study provides data of both physiological and physiopathological relevance. Overall, our data indicated that adjustment of the dexamethasone dose to body weight does not seem to substantially improve the sensitivity of the test, even in obese individuals, particularly w...

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The Hypothalamic‐Pituitary‐Adrenal Axis in Obesity

Cited by 48 publications

References 113 publications

ACTH and cortisol response to combined corticotropin releasing hormone-arginine vasopressin stimulation in obese males and its relationship to body weight, fat distribution and parameters of the metabolic syndrome

ACTH and cortisol response to combined corticotropin releasing hormone-arginine vasopressin stimulation in obese males and its relationship to body weight, fat distribution and parameters of the metabolic syndrome

Effects of Leptin and Corticosterone on the Expression of Corticotropin-Releasing Hormone, Agouti-Related Protein, and Proopiomelanocortin in the Brain of <i>ob/ob</i> Mouse

Cortisol and ACTH Response to Oral Dexamethasone in Obesity and Effects of Sex, Body Fat Distribution, and Dexamethasone Concentrations: A Dose-Response Study

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