DHEA and DHEA‐S: A Review

Kroboth, Patricia D.; Salek, Firoozeh S.; Pittenger, Amy L.; Fabian, Tanya J.; Frye, Reginald F.

doi:10.1177/00912709922007903

Cited by 481 publications

(386 citation statements)

References 131 publications

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“…DHEAS is more soluble in water than DHEA, is converted to DHEA in the cerebral tissue (Kroboth et al, 1999), and is reported to affect the brain neurotransmitter receptors (GABA A R, NMDAR, s1R) in the same mode as DHEA (Majewska, 1992;Monnet et al, 1995;Urani et al, 2001). Therefore, DHEAS was used for the direct intrabrain administration.…”

Section: Discussionmentioning

confidence: 99%

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Genud

Merenlender

Gispan-Herman

et al. 2008

Neuropsychopharmacol

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Alterations in the levels of dehydroepiandrosterone (DHEA) in the brain can allosterically modulate g-aminobutyric-acid-type-A (GABA A R), N-methyl-D-aspartate (NMDAR), and Sigma-1 (s1R) receptors. In humans, DHEA has antidepressive effects; however, the mechanism is unknown. We examined whether alterations in DHEA also occur in an animal model of depression, the Flinders-sensitiveline (FSL) rats, with the intention of determining the brain site of DHEA action and its antidepressant mechanism. We discovered that DHEA levels were lower in some brain regions involved with depression of FSL rats compared to Sprague-Dawley (SD) controls. Moreover, DHEA (1 mg/kg IP for 14 days)-treated FSL rats were more mobile in the forced swim test than FSL controls. In the NAc and VTA, significant changes were observed in the levels of the d-subunit of GABA A , but not of s1R mRNA, in FSL rats compared to SD rats. The d-subunit controls the sensitivity of the GABA A R to the neurosteroid. Indeed, treatment (14 days) of FSL rats with the GABA A agonist muscimol (0.5 mg/kg), together with DHEA (a negative modulator of GABA A ), reversed the effect of DHEA on immobility in the swim test. Perfusion of DHEA sulfate (DHEAS) (3 nM and 30 nM for 14 days) into the VTA and NAc of FSL rats improved their performance in the swim test for at least 3 weeks post-treatment. Our results imply that alterations in DHEA are involved in the pathophysiology of depression and that the antidepressant action of DHEA is mediated via GABA A Rs in the NAc and VTA.

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Section: Discussionmentioning

confidence: 99%

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

Genud

Merenlender

Gispan-Herman

et al. 2008

Neuropsychopharmacol

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“…DHEAS is much more abundant than DHEA, because DHEAS has longer half-life and lower clearance (Lennartsson et al, 2012). Because DHEAS levels are also more stable and show no diurnal variation (Kroboth et al, 1999), they are often preferred in studies on long term effects of stress. Studies on acute stress, on the other hand, often assess DHEA, since DHEAS serves as a reservoir for DHEA biosynthesis and DHEA rather than DHEAS is expected to respond to acute psychosocial stress (Izawa et al, 2008;Morgan et al, 2004;Oberbeck et al, 1998;Pico-Alfonso et al, 2004;Shirotsuki et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

The role of acute cortisol and DHEAS in predicting acute and chronic PTSD symptoms

Mouthaan

Sijbrandij²,

Luitse

et al. 2014

Psychoneuroendocrinology

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SummaryBackground: Decreased activation of the hypothalamus-pituitary-adrenal (HPA) axis in response to stress is suspected to be a vulnerability factor for posttraumatic stress disorder (PTSD). Previous studies showed inconsistent findings regarding the role of cortisol in predicting PTSD. In addition, no prospective studies have examined the role of dehydroepiandrosterone (DHEA), or its sulfate form DHEAS, and the cortisol-to-DHEA(S) ratio in predicting PTSD. In this study, we tested whether acute plasma cortisol, DHEAS and the cortisol-to-DHEAS ratio predicted PTSD symptoms at 6 weeks and 6 months post-trauma. Methods: Blood samples of 397 adult level-1 trauma center patients, taken at the trauma resuscitation room within hours after the injury, were analyzed for cortisol and DHEAS levels. PTSD symptoms were assessed at 6 weeks and 6 months post-trauma with the Clinician Administered PTSD Scale. Results: Multivariate linear regression analyses showed that lower cortisol predicted PTSD symptoms at both 6 weeks and 6 months, controlling for age, gender, time of blood sampling, injury, trauma history, and admission to intensive care. Higher DHEAS and a smaller cortisol-to-DHEAS ratio predicted PTSD symptoms at 6 weeks, but not after controlling for the same variables, and not at 6 months. Conclusions: Our study provides important new evidence on the crucial role of the HPA-axis in response to trauma by showing that acute cortisol and DHEAS levels predict PTSD symptoms in survivors of recent trauma. #

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“…The two enzymes also showed low K m values (Յ1 mM) for 17-ketosteroids, of which DHEA and its sulfate are known to exert a variety of biological actions. 25,26) 16-Ketoestrone was efficiently reduced by the enzymes. In contrast to the low catalytic efficiency (k cat /K m ) for estrone.…”

mentioning

confidence: 99%

“…37) Thus, the kidney is a major organ that metabolizes DHEA and its sulfate, although further study will be needed to elucidate the relationship between the metabolism and various biological actions of DHEA and its sulfate. 25,26) Furthermore, the expression of the two isoforms of 3(17)a-HSD in mouse brain may be important for controlling the concentrations of neuroactive steroids. DHEA sulfate, a substrate of the enzymes, is not only a positive modulator of the s1 receptor, but also a negative modulator of the GABA A -receptor.…”

mentioning

confidence: 99%

Characterization of Two Isoforms of Mouse 3(17).ALPHA.-Hydroxysteroid Dehydrogenases of the Aldo-Keto Reductase Family

Ishikura

Usami

Nakajima

et al. 2004

Biological & Pharmaceutical Bulletin

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Mouse kidney contains two 3(17)a a-hydroxysteroid dehydrogenases (HSDs) that show essentially the same properties except for their isoelectric points. However, the structural differences and physiological roles of the two enzymes remain unknown. In this study, we have isolated cDNAs for the two 3(17)a a-HSDs from a total RNA sample of mouse kidney by reverse transcription-PCR. The identity of the cDNAs was confirmed by characterization of the recombinant enzymes that showed the same molecular weights, pI values, pH optima, substrate specificity and inhibitor sensitivity as those of the enzymes from mouse kidney. We also found that the recombinant enzymes reduce precursors of neuroactive progesterone derivatives, 5a a-dihydrotestoserone, deoxycorticosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate and estrone at low K m values of 0.3-2 m mM. The two enzymes belonged to the aldo-keto reductase (AKR) family, and their 323-amino acid sequences differed only by five amino acids. The sequences of the two isoforms are identical to those of proteins that are predicted to be encoded in a gene for AKR1C21 in the database of the mouse genome. However, the mRNAs for the two isoforms were expressed in mouse kidney and other tissues, in which their expression levels were different. The results indicate an important role of 3(17)a a-HSD in controlling the concentrations of various steroid hormones in the mouse tissues, and suggest the existence of two genes for the two isoforms of the enzyme.

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DHEA and DHEA‐S: A Review

Cited by 481 publications

References 131 publications

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

DHEA Lessens Depressive-Like Behavior via GABA-ergic Modulation of the Mesolimbic System

The role of acute cortisol and DHEAS in predicting acute and chronic PTSD symptoms

Characterization of Two Isoforms of Mouse 3(17).ALPHA.-Hydroxysteroid Dehydrogenases of the Aldo-Keto Reductase Family

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