Selective conversion by microglia of dehydroepiandrosterone to 5-androstenediol—A steroid with inherent estrogenic properties

Jellinck, Peter H.; Kaufmann, Martin; Gottfried-Blackmore, Andrés; McEwen, Bruce S.; Jones, Glenville; Bulloch, Karen

doi:10.1016/j.jsbmb.2007.04.004

Cited by 38 publications

(38 citation statements)

References 40 publications

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“…Although these pathways are shared by microglia, this cell type is not able to produce PREG or PROG. Moreover, expressing 17b-HSD, they synthesize androstenediol from DHEA (Jellinck et al 2007) and testosterone from androstenedione (Jellinck et al 2006(Jellinck et al , 2007. Finally, since ARO is not expressed, microglial cells produce estradiol only from estrone and not from testosterone .…”

Section: Neuroactive Steroids: State Of the Artmentioning

confidence: 99%

Neuroactive steroids, their metabolites, and neuroinflammation

Giatti¹,

Boraso²,

Melcangi³

et al. 2012

Journal of Molecular Endocrinology

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Neuroinflammation represents a common feature of many neurodegenerative diseases implicated both in their onset and progression. Neuroactive steroids act as physiological regulators and protective agents in the nervous system. Therefore, the attention of biomedical research has been recently addressed in evaluating whether neuroactive steroids, such as progestagens, androgens, and estrogens may also affect neuroinflammatory pathways. Observations so far obtained suggest a general anti-inflammatory effect with a beneficial relapse on several neurodegenerative experimental models, thus confirming the potentiality of a neuroprotective strategy based on neuroactive steroids. In this scenario, neuroactive steroid metabolism and the sophisticated machinery involved in their signaling are becoming especially attractive. In particular, because metabolism of neuroactive steroids as well as expression of their receptors is affected during the course of neurodegenerative events, a crucial role of progesterone and testosterone metabolites in modulating neuroinflammation and neurodegeneration may be proposed. In the present review, we will address this issue, providing evidence supporting the hypothesis that the efficacy of neuroactive steroids could be improved through the use of their metabolites.

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Section: Neuroactive Steroids: State Of the Artmentioning

confidence: 99%

Neuroactive steroids, their metabolites, and neuroinflammation

Giatti¹,

Boraso²,

Melcangi³

et al. 2012

Journal of Molecular Endocrinology

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show abstract

“…Saijo et al (Saijo et al, 2011) found that D 5 -androstenediol inhibits transcriptional activation of inflammatory response genes in astrocytes and microglia. D 5 -Androstenediol that is synthesized in brain microglia (Gottfried-Blackmore et al, 2008;Jellinck et al, 2007), inhibits inflammation in microglia by recruitment of the corepressor C-terminal binding protein (CtBP) to the steroid-ERb complex. This complex binds to activation protein-1-dependent promoters, inhibiting inflammation.…”

Section: -Androstenediolmentioning

confidence: 99%

“…E2 is synthesized in three enzymatic steps from DHEA (Baker, 2011b). 17b-HSD-type 14 promotes synthesis from DHEA of D 5 -androstenediol (Saijo et al, 2011;Jellinck et al, 2007), which appears to be an important estrogen in postmenopausal women (Lasley et al, 2011. 5a-Androstanediol is synthesized from 5a-dihydrotestosterone (DHT), and 27-hydroxycholesterol is synthesized from cholesterol.…”

Section: A-androstanediol and D 5 -Androstenediol: Estrogens In The mentioning

confidence: 99%

Estrogen Physiology from an Evolutionary Perspective

Baker

2014

Reference Module in Biomedical Sciences

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“…The concept of widely varying cell-and tissue-specific steroid metabolism is illustrated by the differences in metabolism of DHEA in different CNS cell types. Thus, whereas rat microglia, a cell type important for brain immune function, is reported to exclusively convert this steroid to Aenediol, the major route for DHEA metabolism in rat astrocytes seems to be 7-hydroxylation, carried out by CYP7B1 (Fex Svenningsen et al, 2011;Jellinck et al, 2001;Jellinck et al, 2007). In contrast, the pathways using DHEA as an obligatory precursor for formation of testosterone and estradiol (see Introductory section), are much more dominant in cells outside the brain and are indeed essential for the development and functions of many endocrine organs.…”

Section: Actions Of Cyp7b1 -Potential Role(s) For the Levels And Effementioning

confidence: 99%

“…The total body levels of sex hormones are regulated by signalling from the pituitary and by mechanisms for excretion by the kidneys or in the bile (Bourdeau & Stratakis, 2002;Hum et al, 1999;Waxman & Holloway, 2009). In addition, cell-specific factors and mechanisms are important for regulation of the local sex hormone synthesis and elimination (Jellinck et al, 2007;Norlin, 2008;Penning et al, 2000;Reddy, 2004). Estrogens and androgens are removed from the body via metabolism into inactive metabolites that are excreted in the urine and/or feces.…”

Section: Introductionmentioning

confidence: 99%