Pulsatile secretion of ACTH and cortisol in premenopausal women: effect of obesity and body fat distribution

Pasquali, Renato; Biscotti, Domenico; Spinucci, Giulio; Vicennati, Valentina; Genazzani, Alessandro D.; Sgarbi, L.; Casimirri, Francesco

doi:10.1046/j.1365-2265.1998.00458.x

Cited by 55 publications

(46 citation statements)

References 33 publications

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“…The CRH-ACTH system appears to be activated in obesity, although the number of studies in which spontaneous plasma ACTH secretion patterns were analyzed is rather limited (10,12,33,39). Elevated CRH in obese subjects is likely responsible for the increased ACTH secretion.…”

Section: Discussionmentioning

confidence: 99%

Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women

Roelfsema

Pijl

Keenan

et al. 2012

European Journal of Endocrinology

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Background: The ACTH-cortisol axis in women is activated and associated with decreased ACTH potency, estimated by relating ACTH and cortisol pulse masses. Recently, a new accurate method for constructing the endogenous dose-response relationship was introduced, which is based on the relation between ACTH concentrations and associated cortisol secretion rates within cortisol bursts. Hypothesis: The endogenous dose-response relation between ACTH and cortisol in obesity is changed, leading to diminished responsiveness. Subjects: Twenty-five obese premenopausal women and 16 normal weight premenopausal women were studied by 10-min blood sampling for 24 h. Outcomes: ACTH and cortisol secretion rates, analytical dose-response estimates of endogenous ACTH efficacy (maximal cortisol secretion), dynamic ACTH potency, and adrenal sensitivity (slope term) from 24-h ACTH-cortisol profiles were quantified. Results: The initial potency (negative logarithm) was K7.83G0.75 (meanGS.E.M.) in obese women and K10.14G1.08 in lean women (PZ0.10), and the corresponding values for the recovery phase were K26.62G2.21 and K36.67G1.66 (PZ0.004). The sensitivity (curve slope) amounted to 0.468G0.05 in obese women and 0.784G0.09 in normal weight women (PZ0.004). The efficacy (maximal value) was 17.6G4.9 nmol/l per min in obese women and 26.3G3.8 nmol/l per min in normal weight women (PZ0.009). Basal secretion rate, inflection point, and EC 50 values were not different. Bromocriptine or acipimox did not change the dose-response curve. Conclusion: The ACTH-cortisol relation in obesity in women is characterized by decreased sensitivity and efficacy, thus explaining non-elevated serum cortisol concentrations despite increased plasma ACTH levels.

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Section: Discussionmentioning

confidence: 99%

Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women

Roelfsema

Pijl

Keenan

et al. 2012

European Journal of Endocrinology

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“…To represent the individually secreted amount of cortisol (Peeke & Chrousos 1995, the resulting area under the curve (AUC) of the morning values (n=4, from waking to 0930 h) was taken and expressed as a concentration. This procedure is valid for both sexes (Pasquali et al 1998).…”

Section: Measuring Devicesmentioning

confidence: 99%

Autonomic cardiovascular regulation in obesity

Laederach‐Hofmann¹,

Mussgay²,

Rüddel³

2000

Journal of Endocrinology

165

121

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Obese persons suffer from an increased mortality risk supposedly due to cardiovascular disorders related to either continuously lowered parasympathetic or altered sympathetic activation. Our cross-sectional correlation study establishes the relationship between obesity and autonomic regulation as well as salivary cortisol levels. Three patient cohorts were sampled, covering ranges of body mass index (BMI) of 27-32 (n=17), 33-39 (n=13) and above 40 kg/m 2 (n=12), and stratified for age, sex and menopausal status. Autonomic cardiovascular regulation was assessed by use of heart rate variability and continuous blood pressure recordings. Spectral analytical calculation (discrete Fourier transformation) yields indices of sympathetic and parasympathetic activation and baroreflex sensitivity. Morning salivary cortisol was concurrently collected. Contrary to expectation, BMI and waist/hip ratio (WHR) were inversely correlated with sympathetic activity. This was true for resting conditions (r= 0·48, P<0·001; r= 0·33, P<0·05 for BMI and WHR respectively) and for mental challenge (r= 0·42, P<0·01 for BMI). Resting baroreflex sensitivity was strongly related to the degree of obesity at rest (BMI: r= 0·35, P<0·05) and for mental challenge (r= 0·53, P<0·001). Salivary cortisol correlated significantly with waist circumference (r= 0·34, P=0·05). With increasing weight, no overstimulation was found but a depression in sympathetic and parasympathetic activity together with a significant reduction in baroreflex functioning and in salivary cortisol levels.

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“…For instance, the study of HPA axis ultradian rhythms in premenopausal, viscerally obese women revealed several abnormalities of ACTH pulsatile secretion (increased pulse frequency and reduced pulse amplitude) which were not accompanied by abnormal mean ACTH concentrations in peripheral blood (Pasquali et al, 1998). Another example is obstructive sleep apnoea; in a recent study, the deconvolution analysis of secretory pulses in the 24h systemic GC profiles of untreated patients revealed longer duration of ACTH and cortisol pulses compared to the same patients when they had been successfully treated with continuous positive airway pressure therapy (Henley et al, 2009b).…”

Section: Altered Hpa Rhythmicity In Stressful Conditions and Human Pamentioning

confidence: 99%

Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics

Kalafatakis

Russell

Ζάρρος³

et al. 2016

Neuroscience & Biobehavioral Reviews

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Glucocorticoids mediate plethora of actions throughout the human body. Within the brain, they modulate aspects of immune system and neuroinflammatory processes, interfere with cellular metabolism and viability, interact with systems of neurotransmission and regulate neural rhythms. The influence of glucocorticoids on memory and emotional behaviour is well known and there is increasing evidence for their involvement in many neuropsychiatric pathologies. These effects, which at times can be in opposing directions, depend not only on the concentration of glucocorticoids but also the duration of their presence, the temporal relationship between their fluctuations, the co-influence of other stimuli, and the overall state of brain activity. Moreover, they are region-and cell type-specific. The molecular basis of such diversity of effects lies on the orchestration of the spatiotemporal interplay between glucocorticoid-and mineralocorticoid receptors, and is achieved through complex dynamics, mainly mediated via the circadian and ultradian pattern of glucocorticoid secretion. More sophisticated methodologies are therefore required to better approach the study of these hormones and improve the effectiveness of glucocorticoid-based therapeutics.

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Pulsatile secretion of ACTH and cortisol in premenopausal women: effect of obesity and body fat distribution

Cited by 55 publications

References 33 publications

Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women

Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women

Autonomic cardiovascular regulation in obesity

Temporal control of glucocorticoid neurodynamics and its relevance for brain homeostasis, neuropathology and glucocorticoid-based therapeutics

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