Serotoninergic receptor activation by dextrofenfluramine enhances the blunted pituitary-adrenal responsiveness to corticotropin-releasing hormone in obese subjects

Bernini, Giampaolo; Argenio, G. F.; Corso, C. Del; Vivaldi, M. S.; Birindelli, R.; Franchi, F

doi:10.1016/0026-0495(92)90184-c

Cited by 9 publications

(5 citation statements)

References 37 publications

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“…The remaining studies on the HPA axis in the literature [36 ± 45] all deal with "internal stimulabil− ity" ± the response of ACTH and/or cortisol levels to stimulation with CRH (corticotropin−releasing hormone) or vasopressin, or the response of cortisol levels to stimulation with ACTH. Most of these studies have suggested sluggishness in some of the inter− nal steps in HPA axis stimulability [36,37,39,42,44], which is in line with reported sluggishness in the hypothalamic−pituitary control mechanisms for several other hormones (growth hor− mone, prolactin, vasopressin, and b−endorphin) in obesity [46].…”

Section: The Hypothalamic−pituitary−adrenal (Hpa) Axissupporting

confidence: 53%

Obesity and Cortisol Status

2005

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The fact, that obesity is a prominent feature of hypercortisolism (Cushing's syndrome) has stimulated investigation on the possible existence of the reverse relationship, namely that hypercortisolism is a feature of obesity. We have reviewed half a century of literature on this question, and have found out the following: (1) Hypercortisolism can exist in two forms: systemic hypercortisolism, in which there is an overall bodily excess of cortisol, and tissue, or intracellular, hypercortisolism, in which there is increased intracellular concentration of cortisol without an overall bodily excess. (2) There are two parameters of systemic hypercortisolism: CPR and plasma cortisol concentration. Proper evaluation of the first parameter requires correction for the active metabolic mass, which is best performed by expressing CPR per gram of urinary creatinine. The second parameter can be confounded by the marked moment-to-moment fluctuations in plasma cortisol concentrations due to cortisol's episodic secretion. Proper evaluation requires measuring the 24-hour mean concentration. Of these two parameters of systemic cortisol status, the plasma concentration is the more critical and accurate. (3) Corrected CPR is normal in obese individuals, and 24-hour mean plasma cortisol concentrations are slightly but definitely subnormal. This combination of findings indicates diminished stimulability of the hypothalamic-pituitary-adrenal (HPA) axis, which normally regulates bodily cortisol status. This deduction is supported by empirical studies on HPA reactivity. (4) Tissue hypercortisolism, due to increased intracellular activity of 11beta-HSD-1, which catalyzes reduction of cortisone to cortisol, has been reported in obese mice and humans. The findings of various studies are not consistent, and whether the enzymatic overactivity is a cause or a result of obesity is still unclear.

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Section: The Hypothalamic−pituitary−adrenal (Hpa) Axissupporting

confidence: 53%

Obesity and Cortisol Status

2005

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“…Furthermore, the exaggerated ACTH response to oral glucose in subjects with abdominal obesity is incompatible with the pituitary cause of hypocortisolism. Thus, we are left with the possibility of a hypothalamic or central adrenal insufficiency as the cause of hypocortisolism in abdominal obesity ; this may result from diminished CRH or some other neuropeptide or neurotransmitter, such as serotonin [19], which is known to regulate the pituitaryadrenal axis. Based in part on a qualitatively similar pattern of alterations in the HPA axis, the same conclusion has recently been drawn regarding the aetiology of hypocortisolism in chronic fatigue syndrome [20].…”

Section: Discussionmentioning

confidence: 99%

Altered adrenocorticotropin and Cortisol secretion in abdominal obesity: implications for the insulin resistance syndrome

Hautanen

Adlercreutz

1993

Journal of Internal Medicine

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“…Dextrofenfluramine enhances serotonin release and inhibits serotonin reuptake. Treatment with dextrofenfluramine enhances the previously blunted cortisol responses to CRH in obese women (7). This may indicate reduced serotoninergic activity in obese subjects which may influence the responsiveness of HPA function.…”

Section: Serotonin Stimulationmentioning

confidence: 92%

“…ACTH and cortisol responses to CRH were found to be similar in obese and lean children (6). In adults one study reported that the peak ACTH response to CRH of obese and lean were similar (65,116) while a separate study found a reduced ACI'H response in obese patients (7). In adults, the peak cortisol response to CRH was significantly reduced in obese compared to lean controls (7,46,65).…”

Section: Corticotropin Releasing Hormone (Crh)mentioning

confidence: 95%

“…In adults one study reported that the peak ACTH response to CRH of obese and lean were similar (65,116) while a separate study found a reduced ACI'H response in obese patients (7). In adults, the peak cortisol response to CRH was significantly reduced in obese compared to lean controls (7,46,65). The diminished cortisol response was not related to the dose of CRH as the cortisol response was not significantly altered by doubling the dose (65).…”

Section: Corticotropin Releasing Hormone (Crh)mentioning

confidence: 99%

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