Metabolism of dehydroepiandrosterone by rodent brain cell lines: Relationship between 7-hydroxylation and aromatization

Cytochrome P450 17α-hydroxylase/C(17,20)-lyase immunoreactivity and molecular expression in the cerebellar nuclei of adult male rats

“…skin, liver and brain) (Labrie, 2004). The neurobiological activities of estradiol and testosterone are well documented (Rupprecht, 2003;Jellinck et al, 2005Jellinck et al, , 2006Mukai et al, 2006;Tsutsui, 2008); however, focusing on actions attributable directly to DHEA and its proposed mechanisms of action, few studies have analyzed its neurobiological activity in the cerebellum and, more specifically, at the level of the DCN. A study was performed on cerebellar granule cells where DHEA exerted significant neuroprotective effect by preventing neuronal mitochondrial damage due to calcium overload (Kaasik et al, 2003), and mitigating the neurotoxicity of substances such as glutamate, N-methyl-D-aspartate, 1-methyl-4-phenylpyridinum and colchicine (Kaasik et al, 2001).…”

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

“…Approximately 3 × 10 5 cells were plated [14] and incubated in 0.6-1.2 ng of [ 3 H]DHEA for 22 h in 0.2 ml of Dulbecco's modified eagle medium (DMEM, Invitrogen) supplemented with 4 mM glutamine. All incubations were conducted in a humidified atmosphere of 5% CO 2 in air at 37 • C. The reaction was stopped by vortexing the supernatant with 0.2 ml acetone and 0.5 ml ethyl acetate.…”

“…In the brain, DHEA's neuroprotective action [3,4] is Abbreviations: DHEA, dehydroepiandrosterone, 3␤-hydroxy-5-androstene-17-one; AD, 4-androstene-3,17-dione; 5 -Adiol, 5-androstene-3␤,17␤-diol; 5␣-Adione, 5␣-androstane-3,17-dione; T, testosterone; DHT, dihydrotestosterone, 5␣-androstane-3-one-17␤-ol; 7␣-OH-DHEA, 7␣-hydroxy-DHEA; 17␤-HSD, 17␤-hydroxysteroid dehydrogenase; 3␤-HSD/KSI, 3␤-hydroxysteroid dehydrogenase/ketosteroid isomerase; TLC, thin layer chromatography; HPLC, high performance liquid chromatography; RT-PCR, real-time reverse transcriptase polymerase chain reaction generally attributed to its conversion to estrogen [5,6] which is known to protect hippocampal neurons [7][8][9] and enhances memory and learning [10][11][12]. However, the conversion of DHEA to 4-androstenedione (AD), a precursor necessary for the formation of estrogens, is very slow and limited in cultured hippocampal neurons and in other types of brain cells, with the main product of this reaction determined to be its 7␣-hydroxylated derivative (7␣-OH-DHEA) [13,14]. A notable exception to these findings is observed with microglia.…”

The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines

“…De plus, ce stéroïde également produit au niveau de l'hippocampe par le CYP7B1 pourrait jouer un rôle dans la maladie d'Alzheimer. En effet, une diminution de l'activité du CYPB1 et, par conséquent du taux de 7α-hydroxy-DHEA, contribuerait au développement de la maladie (Yau et al, 2003 ;Jellinck et al, 2005).…”