Dehydroepiandrosterone: Antiglucocorticoid Action in Mice

Browne, Elizabeth; Wright, Bruce E.; Porter, Johnny R.; Švec, František

doi:10.1097/00000441-199206000-00003

Cited by 80 publications

(29 citation statements)

References 30 publications

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“…Third, there is evidence that DHEA has significant antiglucocorticoid properties by antagonizing glucocorticoid actions in several animal models (18,19), and that this steroid lowers circulating glucocorticoid levels in humans (20,21). Obviously, we cannot rule out an adaptive, cortisol-antagonizing effect of elevated DHEA in our hypercortisolemic patients because we did not study the time sequence of the hormonal changes in our patients.…”

Section: Discussionmentioning

confidence: 94%

Increased Diurnal Plasma Concentrations of Dehydroepiandrosterone in Depressed Patients

Heuser

Deuschle

Luppa

et al. 1998

The Journal of Clinical Endocrinology & Metabolism

106

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Activation of the hypothalamus-pituitary-adrenocortical system is a biological core symptom of depression. Although the regulation of cortisol secretion is well studied in this condition, there is no information about the diurnal activity of dehydroepiandrosterone (DHEA) secretion. Therefore, we studied 24-h DHEA plasma concentrations (every 30 min) in severely depressed patients (n ϭ 26) and healthy controls (n ϭ 33).We found depression to significantly increase diurnal minimal and mean DHEA plasma concentrations, whereas there was no effect on the diurnal maximal plasma concentration and the diurnal amplitude of DHEA. In particular, we found a parallel increase in mean DHEA (5.8 Ϯ 3.6 vs. 3.4 Ϯ 1.9 nmol/L; P Ͻ 0.003), cortisol (286 Ϯ 65 vs. 184 Ϯ 29 nmol/L; P Ͻ 0.0001) and ACTH (7.14 Ϯ 2.06 vs. 5.72 Ϯ 1.36 pmol/L; P Ͻ 0.002) plasma concentrations.The novel finding of parallel increases in diurnal DHEA and cortisol plasma concentrations in depressed patients has important implications for the regulation of the hypothalamus-pituitary-adrenocortical system in conditions of chronic stress and for the rationale of DHEA treatment in depressed patients. (J Clin Endocrinol Metab 83: 3130 -3133, 1998) T HE ADRENAL cortex secretes various steroid hormones with differing glucocorticoid, mineralocorticoid, and androgen properties. Neuroendocrine studies in affective disorders are mainly focussed on the well known hypercortisolemia as a consequence of the dysregulation of the hypothalamus-pituitary-adrenocortical (HPA) system, which is evident from studies of basal secretory activity (1) and feedback regulation (2). However, there is only sparse information about the regulation of the secretion of other adrenal steroid hormones in depression, especially dehydroepiandrosterone (DHEA), whose sulfated form (DHEAS) is the most abundant steroid hormone in man.Studies using single point measurements found that plasma DHEA and DHEAS concentrations were not different in depressed patients and healthy controls (3, 4). In contrast, in a small group of depressed patients with psychotic features, plasma DHEA was increased (5). This finding is in accordance with a report about elevated 24-h urinary DHEAS (6) in depressed patients.It is assumed that ACTH is an important regulator of the secretion of adrenal androgens. However, there are several instances, such as adrenarche, puberty, normal aging, and acute stress, where a dissociation between the effects of ACTH on adrenal androgens, such as DHEA, and adrenal glucocorticoids, such as cortisol, has been observed (7-9).Additionally, clarifying the specific features of the regulation of DHEA in depressed patients seems necessary to better understand the possibly beneficial effect of DHEA treatment in this group of patients (10). Therefore, we studied diurnal profiles of DHEA in a large group of drug-free depressed patients and in a gender-and age-matched group of healthy controls. Subjects and Methods SubjectsThis study was approved by the local ethics committee, and all subje...

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Section: Discussionmentioning

confidence: 94%

Increased Diurnal Plasma Concentrations of Dehydroepiandrosterone in Depressed Patients

Heuser

Deuschle

Luppa

et al. 1998

The Journal of Clinical Endocrinology & Metabolism

106

View full text Add to dashboard Cite

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“…Whereas cortisol is a glucocorticoid, DHEA has antiglucocorticoid properties that appear to protect neurons [Blauer et al, 1991;Browne et al, 1992]. For example, research on metabolites of DHEA in the brain suggests that they interfere with uptake of activated glucocorticoid receptors [Morfin and Starka, 2001].…”

Section: Biological Measures Of Resiliencementioning

confidence: 99%

Resilience: research evidence and conceptual considerations for posttraumatic stress disorder

2007

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The growing recognition and occurrence of traumatic exposure in the general population has given increased salience to the need to understand the concept of resilience. More than just the "flip side" of a risk factor, the notion of resilience encompasses psychological and biological characteristics, intrinsic to an individual, that might be modifiable and that confer protection against the development of psychopathology in the face of stress. In this review, we provide some perspective on the concept of "resilience" by examining early use of the term in research on "children at risk" and discuss the relationship between risk and resilience factors. We then review psychological and biological factors that may confer resilience to the development of posttraumatic stress disorder (PTSD) following trauma, examine how resilience has been assessed and measured, and discuss issues to be addressed in furthering our understanding of this critical concept going forward.

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“…DHEA(S) does have antiglucocorticoid effects as it inhibits glucocorticoid induced enzyme activity (Browne et al 1992) and antagonizes dexamethasone-induced suppression of lymphocytes and thymic involution (Kalimi et al 1994). In addition, administration of DHEA has been shown to decrease plasma cortisol levels (Wolkowitz et al 1992;Wolf et al 1997).…”

Section: Antiglucocorticoid Effects Of Dheamentioning

confidence: 99%