Ergosteroids II: Biologically Active Metabolites and Synthetic Derivatives of Dehydroepiandrosterone 11This work was supported by Humanetics Corp., St. Louis Park, Minnesota.

Lardy, Henry A.; Kneer, Nancy; Wei, Yuming; Partridge, Bruce; Marwah, Padma

doi:10.1016/s0039-128x(97)00159-1

Cited by 54 publications

(18 citation statements)

References 57 publications

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“…DHEA derivatives listed in Table 1 were synthesized and characterized as described (24,25) Immunocytochemistry. Cultures were fixed in ice cold methanol for 20 min or 4% paraformaldehyde (PFA in PBS) at room temperature and washed in PBS.…”

Section: Methodsmentioning

confidence: 99%

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Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex

Suzuki

Wright

Marwah

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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143

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Dehydroepiandrosterone (DHEA) is a neurosteroid with potential effects on neurogenesis and neuronal survival in humans. However, most studies on DHEA have been performed in rodents, and there is little direct evidence for biological effects on the human nervous system. Furthermore, the mechanism of its action is unknown. Here, we show that DHEA significantly increased the growth rates of human neural stem cells derived from the fetal cortex and grown with both epidermal growth factor (EGF) and leukemia inhibitory factor (LIF). However, it had no effect on cultures grown in either factor alone, suggesting a specific action on the EGF͞LIF-responsive cell. Precursors of DHEA such as pregnenolone or six of its major metabolites, had no significant effect on proliferation rates. DHEA did not alter the small number (<3%) of newly formed neuroblasts or the large number (>95%) of nestin-positive precursors. However, the number of glial fibrillary acidic protein-positive cells, its mRNA, and protein were significantly increased by DHEA. We found both N-methyl-D-aspartate and sigma 1 antagonists, but not GABA antagonists, could completely eliminate the effects of DHEA on stem cell proliferation. Finally we asked whether the EGF͞LIF͞DHEA-responsive stem cells had an increased potential for neurogenesis and found a 29% increase in neuronal production when compared to cultures grown in EGF͞LIF alone. Together these data suggest that DHEA is involved in the maintenance and division of human neural stem cells. Given the wide availability of this neurosteroid, this finding has important implications for future use.

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Section: Methodsmentioning

confidence: 99%

“…DHEA is readily converted metabolically to derivatives that are more active in some assays (24,30,31). In rat liver homogenate, the sequence is DHEA 3 7␣-OH-DHEA 3 7-oxo-DHEA 3 7␤-OH-DHEA 3 androst-5-en-3␤,7␤,17␤-triol.…”

Section: Other Active Components Of the Dhea Pathway Do Not Affect Thementioning

confidence: 99%

Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex

Suzuki

Wright

Marwah

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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143

136

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“…Adiol, DHT, 17␤-estradiol, and progesterone were purchased from Sigma; ethynyl-derivatized steroids were from Steraloids (Wilton, NH); HF (Eulexin) was provided by G. Wilding (University of Wisconsin, Madison, WI); pSG5-WtAR and MMTV-CAT were constructed as described (6). Other steroid compounds, derivatives of DHEA, were synthesized; some have been described (19,20).…”

Section: Methodsmentioning

confidence: 99%

Suppression of Δ ⁵ -androstenediol-induced androgen receptor transactivation by selective steroids in human prostate cancer cells

Chang

Miyamoto²,

Marwah

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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“…For instance, common adverse effects in women taking 200 mg of DHEA per day include acne and hirsutism. These effects may be averted, however, by administering 7-keto DHEA, which is not converted to sex hormones [97] and reduces ethanol intake similarly to DHEA [96]. …”

Section: Discussionmentioning

confidence: 99%

“…To address these questions, Worrel et al [96] administered 7-keto DHEA, a metabolite of DHEA that is not metabolized to testosterone or estradiol [97], to the subjects from the Gurkovskaya et al [95] preference study and found that this compound produced effects as large as DHEA. In fact, while 10 mg/kg of 7-keto DHEA produced an effect comparable to DHEA, 56 mg/kg of 7-keto DHEA produced a larger decrease in ethanol intake than DHEA.…”

Section: Dhea Decreases Ethanol Intakementioning

confidence: 99%

Neurosteroid Binding Sites on the GABA_AReceptor Complex as Novel Targets for Therapeutics to Reduce Alcohol Abuse and Dependence

Hulin

Amato

Porter

et al. 2011

Advances in Pharmacological Sciences

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Despite the prevalence of alcohol abuse and dependence in the US and Europe, there are only five approved pharmacotherapies for alcohol dependence. Moreover, these pharmacotherapeutic options have limited clinical utility. The purpose of this paper is to present pertinent literature suggesting that both alcohol and the neurosteroids interact at the GABAA receptor complex and that the neurosteroid sites on this receptor complex could serve as new targets for the development of novel therapeutics for alcohol abuse. This paper will also present data collected by our laboratory showing that one neurosteroid in particular, dehydroepiandrosterone (DHEA), decreases ethanol intake in rats under a variety of conditions. In the process, we will also mention relevant studies from the literature suggesting that both particular subtypes and subunits of the GABAA receptor play an important role in mediating the interaction of neurosteroids and ethanol.

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Ergosteroids II: Biologically Active Metabolites and Synthetic Derivatives of Dehydroepiandrosterone 11This work was supported by Humanetics Corp., St. Louis Park, Minnesota.

Cited by 54 publications

References 57 publications

Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex

Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex

Suppression of Δ ⁵ -androstenediol-induced androgen receptor transactivation by selective steroids in human prostate cancer cells

Neurosteroid Binding Sites on the GABA_AReceptor Complex as Novel Targets for Therapeutics to Reduce Alcohol Abuse and Dependence

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Ergosteroids II: Biologically Active Metabolites and Synthetic Derivatives of Dehydroepiandrosterone 11This work was supported by Humanetics Corp., St. Louis Park, Minnesota.

Cited by 54 publications

References 57 publications

Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex

Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex

Suppression of Δ 5 -androstenediol-induced androgen receptor transactivation by selective steroids in human prostate cancer cells

Neurosteroid Binding Sites on the GABAAReceptor Complex as Novel Targets for Therapeutics to Reduce Alcohol Abuse and Dependence

Contact Info

Product

Resources

About

Suppression of Δ ⁵ -androstenediol-induced androgen receptor transactivation by selective steroids in human prostate cancer cells

Neurosteroid Binding Sites on the GABA_AReceptor Complex as Novel Targets for Therapeutics to Reduce Alcohol Abuse and Dependence