The Pituitary Response to Ovine Corticotropin-Releasing Hormone is Enhanced in Obese Men and Correlates with Insulin Resistance

Solano, Maria P.; Kumar, Mahendra; Fernández, Begoña; Jones, Linda; Goldberg, Robert B.

doi:10.1055/s-2001-12625

Cited by 22 publications

(12 citation statements)

References 19 publications

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“…19 Our data, in the context of previous studies 2 on premenopausal women, are consistent with its suggestion that the menopause may result in a diminished response to CRH. However, the lack of a relationship of central obesity to CRH responses in women may re¯ect the narrow range of STR in the female group, as compared to the male group in our study.…”

Section: Interleukin-6supporting

confidence: 80%

Central obesity, depression and the hypothalamo–pituitary–adrenal axis in men and postmenopausal women

Katz¹,

Taylor

Goodrick³

et al. 2000

Int J Obes

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OBJECTIVE: We examined the relationship of adiposity to pituitary ± adrenal responses to corticotrophin-releasing hormone (CRH) in men and postmenopausal women, controlling for the in¯uence of depression. DESIGN: Studies of CRH responses, cortisol metabolite levels and depression scores in relation to adiposity in men and postmenopausal women. SUBJECTS: Thirteen men: age (median, interquartile range) 62 y (52 ± 63), body mass index (BMI) 29.0 kgam 2 (26.3 ± 33.1), waist circumference (waist) 105 cm (97 ± 111), waist : hip ratio (WHR) 1.03 (0.98 ± 1.07), subscapular to triceps skinfold thickness ratio (STR) 2.0 (1.2 ± 2.4), total body fat (TBF) 25.4 kg (19.8 ± 28.8); and eight women: age 54 y (53 ± 62), BMI 30 kgam 2 (23 ± 41), waist 86 cm (79 ± 117), WHR 0.94 (0.87 ± 1.10), STR 1.0 (0.85 ± 1.07), TBF 35.0 kg (18.7 ± 48.8). MEASUREMENTS: A standard CRH test was conducted with additional basal samples taken for leptin and interleukin 6 (IL-6). Total urine cortisol metabolites (TCM) and the ratio of urinary cortisol : cortisone (FmaEm) metabolites were measured. Depression scores were measured by the General Health Questionnaire (GHQ-30) and Hospital Anxiety and Depression Scale (HAD) questionnaire. All subjects completed an overnight dexamethasone suppression test. RESULTS: The basal to peak percentage increments (%inc.) in adrenocorticotrophic hormone (ACTH) and cortisol in men correlated directly with STR (ACTH %inc. r 0.70, P`0.01; cortisol %inc. r 0.55, P 0.05); this relationship was independent of depression scores. In women, the ACTH area under incremental curve (AUIC) correlated negatively with STR (r À0.81, P`0.05). In men, but not in women, there was a signi®cant correlation between GHQ-30 score and ACTH AUIC (r 0.62, P`0.05) and cortisol AUIC (r 0.72, P`0.01). Depression scores were consistently and directly related to indices of obesity and central obesity. There were no signi®cant relationships in either sex between urinary TCM or FmaEm ratio and BMI, waist, WHR, TBF, STR or CRH responses. The urinary FmaEm ratio was higher in men than in women (median 0.74 vs 0.66, P`0.05). In men, but not in women, GHQ-30 scores correlated positively with urinary TCM (r 0.57, P 0.05) and HAD-depression scores were inversely related to the urine FmaEm ratio (r À0.65, P`0.05). All subjects suppressed normally with dexamethasone. CONCLUSIONS: Cortisol metabolite levels were increased in depression in men, but were not related to adiposity in either sex. We demonstrate that central obesity in men, but not postmenopausal women, is associated with an enhanced pituitary ± adrenal response to CRH and that this relationship is independent of depression score.

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Section: Interleukin-6supporting

confidence: 80%

Central obesity, depression and the hypothalamo–pituitary–adrenal axis in men and postmenopausal women

Katz¹,

Taylor

Goodrick³

et al. 2000

Int J Obes

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“…Obese rats had lower tissue levels of norepinephrine and higher densities of α 1 -adrenergic-binding sites in the paraventricular nucleus than lean rats [33, 34] and norepinephrine levels in the paraventricular nucleus during and after immobilization stress were lower in obese than in lean male rats [15]. With respect to pituitary responsiveness to CRH and/or AVP, obese men had greater ACTH secretion in response to CRH than lean men [55, 56]. Levels of cortisol following injection of CRH were lower in obese than in normal women [57] or were similar in obese and normal women [58] although these studies did not directly investigate pituitary responsiveness to CRH.…”

Section: Discussionmentioning

confidence: 99%

Responses of the Hypothalamopituitary Adrenal Axis and the Sympathoadrenal System to Isolation/Restraint Stress in Sheep of Different Adiposity

et al. 2008

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There is evidence that levels of adipose tissue can influence responses of the hypothalamopituitary-adrenal (HPA) axis to stress in humans and rats but this has not been explored in sheep. Also, little is known about the sympathoadrenal responses to stress in individuals with relatively different levels of adipose tissue. We tested the hypothesis that the stress-induced activation of the HPA axis and sympathoadrenal system is lower in ovariectomized ewes with low levels of body fat (lean) than ovariectomized ewes with high levels of body fat (fat). Ewes underwent dietary manipulation for 3 months to yield a group of lean ewes (n = 7) with a mean (±SEM) live weight of 39.1 ± 0.9 kg and body fat of 8.9 ± 0.6% and fat ewes (n = 7) with a mean (±SEM) live weight of 69.0 ± 1.8 kg and body fat of 31.7 ± 3.4%. Fat ewes also had higher circulating concentrations of leptin than lean ewes. Blood samples were collected every 15 min over 8 h when no stress was imposed (control day) and on a separate day when 4 h of isolation/restraint was imposed after 4 h of pretreatment sampling (stress day). Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, epinephrine and norepinephrine did not change significantly over the control day and did not differ between lean and fat ewes. Stress did not affect plasma leptin levels. All stress hormones increased significantly during isolation/restraint stress. The ACTH, cortisol and epinephrine responses were greater in fat ewes than lean ewes but norepinephrine responses were similar. Our results suggest that relative levels of adipose tissue influence the stress-induced activity of the hypothalamopituitary-adrenal axis and some aspects of the sympathoadrenal system with fat animals having higher responses than lean animals.

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“…Obese patients with central obesity exhibit hyperactivity of the HPA axis as reflected by an exaggerated ACTH response to corticotropin-releasing hormone (CRH) stimulation. 20 Leptin inhibits stress-responsive secretion of hypothalamic CRH in mice 21 and also regulates adrenal function directly, decreasing steroid hormone release in all 3 zones of the adrenal cortex. 22 One possible explanation for the increased ACTH levels after RYGB could be that the decreased leptin levels after surgery reduce the tonic inhibitory effect of this hormone on the HPA axis.…”

Section: The Role Of Adrenocorticotropic Hormonementioning

confidence: 99%

The Early Effect of the Roux-en-Y Gastric Bypass on Hormones Involved in Body Weight Regulation and Glucose Metabolism

Rubino¹,

Gautier²,

Gentileschi³

et al. 2004

Annals of Surgery

581

372

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Objective: To evaluate the early effect of Roux-en-Y (RYGB) gastric bypass on hormones involved in body weight regulation and glucose metabolism. Significant Background Data: The RYGB is an effective bariatric procedure for which the mechanism of action has not been elucidated yet. Reports of hormonal changes after RYGB suggest a possible endocrine effect of the operation; however, it is unknown whether these changes are the cause or rather the effect of surgically induced weight loss. We speculated that if the mechanism of action of the RYGB involves an endocrine effect, then hormonal changes should occur early after surgery, prior to substantial body weight changes. Methods: Ten patients with a mean preoperative body mass index (BMI) of 46.2 kg/m 2 (40 -53 kg/m 2 ) underwent laparoscopic RYGB. Six patients had type 2 diabetes treated by oral hypoglycemic agents. Preoperatively and 3 weeks following surgery, all patients were tested for fasting glucose, insulin, glucagon, insulinlike growth factor 1 (IGF-1), leptin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), adrenocorticotropic hormone (ACTH), corticosterone, and neuropeptide Y (NPY). Results: Changes in mean BMI were rather minimal (43.2 kg/m 2 ; P ϭ not significant), but there was a significant decrease in blood glucose (P ϭ 0.005), insulin (P ϭ 0.02), IGF-1 (P Ͻ 0.05), leptin (P ϭ 0.001), and an increase in ACTH levels (P ϭ 0.01). The other hormones were not significantly changed by surgery. All the 6 diabetic patients had normal glucose and insulin levels and did not require medications after surgery. The RYGB reduced GIP levels in diabetic patients (P Ͻ 0.01), whereas no changes in GIP levels were found in nondiabetics. Conclusions: Roux-en-Y gastric bypass determines considerable hormonal changes before significant BMI changes take place. These results support the hypothesis of an endocrine effect as the possible mechanism of action of RYGB. S urgery represents the most effective therapeutic modality for morbid obesity.1,2 Interestingly, the Roux-en-Y gastric bypass (RYGB), a procedure that includes the creation of a small proximal gastric pouch and the bypass of the duodenum and proximal jejunum from the transit of food, not only determines permanent reduction of excess body weight, but also induces resolution of type 2 diabetes mellitus in more than 80% of morbidly obese patients. 3Body weight is the result of complex physiologic mechanisms that control food intake and energy expenditure. Regulation of body weight involves several systems such as the adipose tissue, 4 the hypothalamus, 5 and the adrenal glands, 6 which are linked by neural and hormonal signals. Recent investigations have identified several key molecules that regulate food intake, including ghrelin, neuropeptide Y (NPY), 7 and melanocortins 8 and have focused on the relationship between obesity and leptin levels. The effectiveness of gastric bypass in inducing remarkable weight loss and control of diabetes represents an "experimental mod...

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The Pituitary Response to Ovine Corticotropin-Releasing Hormone is Enhanced in Obese Men and Correlates with Insulin Resistance

Cited by 22 publications

References 19 publications

Central obesity, depression and the hypothalamo–pituitary–adrenal axis in men and postmenopausal women

Central obesity, depression and the hypothalamo–pituitary–adrenal axis in men and postmenopausal women

Responses of the Hypothalamopituitary Adrenal Axis and the Sympathoadrenal System to Isolation/Restraint Stress in Sheep of Different Adiposity

The Early Effect of the Roux-en-Y Gastric Bypass on Hormones Involved in Body Weight Regulation and Glucose Metabolism

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