Neurosteroid metabolism in the human brain

Stoffel‐Wagner, Birgit

doi:10.1530/eje.0.1450669

Cited by 452 publications

(175 citation statements)

References 121 publications

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“…glioma cell lines express aromatase and, are, therefore, capable of producing oestrogens from androgens (Stoffel-Wagner, 2001;Yague et al, 2004). The present study demonstrates that melatonin, at 1 mM concentration, reduces the synthesis of oestrogens in C6 glioma cells, through the inhibition of aromatase, the enzyme that catalyses the rate-limiting step in the conversion of androgens into oestrogens (Zhou et al, 1993).…”

Section: Discussionsupporting

confidence: 50%

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Inhibitory effects of pharmacological doses of melatonin on aromatase activity and expression in rat glioma cells

et al. 2007

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Melatonin exerts oncostatic effects on different kinds of neoplasias, especially on oestrogen-dependent tumours. Recently, it has been described that melatonin, on the basis of its antioxidant properties, inhibits the growth of glioma cells. Glioma cells express oestrogen receptors and have the ability to synthesise oestrogens from androgens. In the present study, we demonstrate that pharmacological concentrations of melatonin decreases the growth of C6 glioma cells and reduces the local biosynthesis of oestrogens, through the inhibition of aromatase, the enzyme that catalyses the conversion of androgens into oestrogens. These results are supported by three types of evidence. Firstly, melatonin counteracts the growth stimulatory effects of testosterone on glioma cells, which is dependent on the local synthesis of oestrogens from testosterone. Secondly, we found that melatonin reduces the aromatase activity of C6 cells, measured by the tritiated water release assay. Finally, by (RT) -PCR, we found that melatonin downregulates aromatase mRNA steady-state levels in these glioma cells. We conclude that melatonin inhibits the local production of oestrogens decreasing aromatase activity and expression. By analogy to the implications of aromatase in other forms of oestrogen-sensitive tumours, it is conceivable that the modulation of the aromatase by pharmacological melatonin may play a role in the growth of glioblastomas.

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Section: Discussionsupporting

confidence: 50%

“…Steroids or their precursors can be metabolised in the CNS to derivates which can affect brain function and may have an important clinical significance (Weidenfeld and Schiller, 1984). Previous studies have shown that human brain and human neuronal cell lines secrete oestrogens (Stoffel-Wagner, 2001, 2003.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of pharmacological doses of melatonin on aromatase activity and expression in rat glioma cells

et al. 2007

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“…20 The interaction between steroids and neurotransmitters in the CNS is still an area of active investigation. 21 Steroid hormones easily cross the blood-brain barrier, where extensive steroid metabolism occurs. Neurosteroids, whether originating from outside the CNS or synthesized de novo in the brain, modulate a wide range of neurotransmitters in the brain, including GABA (g-aminobutyric acid), NMDA (N-methyl-d-aspartate), and nicotinic, muscarinic, serotonin (5-HT 3 ), kainate, glycine and sigma receptors.…”

Section: Neurobiology Of Sexual Responsementioning

confidence: 99%

Preclinical effects of melanocortins in male sexual dysfunction

Shadiack¹,

Althof²

2008

Int J Impot Res

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The neurobiology of sexual behavior involves the interrelationships between sex steroids and neurotransmitters that result in both central nervous system (CNS) effects and effects in the genitalia. Tools such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scanning can help determine what areas of the brain are activated under sexual stimulation. Our understanding of the role of various neurotransmitters, neurosteroids and other CNS-acting compounds is improving. The role of CNS-acting compounds such as dopamine agonists in the treatment of male sexual dysfunction is under active investigation. Melanocortins have CNS and peripheral roles in a wide variety of bodily functions. The melanocortin agonist bremelanotide appears to act in the CNS to promote erections in preclinical models, and may also stimulate behaviors that facilitate sexual activity beyond their erectogenic effects.

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“…Overall, it is still possible that the endocrine findings are not related to a diagnostic specificity, and the elevated cortisol/DHEA(S) ratios in schizophrenia patients may be associated with impaired stress-response (Wolf and Kirschbaum, 1999;Boudarene and Legros, 2002;Kimonides et al, 1999) and may lead to dysregulated neurotransmission (Akwa and Baulieu, 2000), resulting in chronic and progressive deterioration in cognitive, emotional, and psychosocial functions (Wen et al, 2001;Johnson et al, 2002). Indeed, clinical investigations produced evidence of the involvement of neuroactive steroids in conditions such as fatigue during pregnancy, premenstrual syndrome, postpartum depression, epilepsy, dementia, depressive, and anxiety disorders (Stoffel-Wagner, 2001;Pisua and Serra, 2004).…”

Section: Commentmentioning

confidence: 99%

Cortisol/Dehydroepiandrosterone Ratio and Responses to Antipsychotic Treatment in Schizophrenia

Ritsner

Gibel

Maayan

et al. 2005

Neuropsychopharmacol

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Dehydroepiandrosterone (DHEA) or their sulfate conjugate (DHEAS) (together abbreviated DHEA(S)) exert multiple effects in the central nervous system, and may be involved in the pathophysiological processes in schizophrenia. This prospective study aimed to investigate whether serum cortisol/DHEA(S) molar ratios are associated with response to antipsychotic treatment during the exacerbation of schizophrenia. Serum DHEA(S) and cortisol were determined at baseline, and 2 and 4 weeks later for 43 medicated schizophrenia inpatients with acute exacerbation. The patients were treated with stable doses of antipsychotic agents up to 2 weeks prior to entering the study and for the 4-week duration of the study after which they were classified as either responders or nonresponders to treatment. Findings suggest that responders had significantly higher serum cortisol levels and cortisol/DHEA(S) ratios compared with nonresponders. These differences remained significant at three time points controlling for gender, age, severity of symptoms and emotional distress, benzodiazepines, type or dosage of antipsychotic agents, and background variables. The logistic regression model shows advantages of both cortisol/DHEA(S) molar ratios vs serum cortisol and DHEA(S) concentrations for prediction of responsivity to antipsychotic treatment. No significant canonical correlations were observed between changes from baseline through end-of-study in hormonal values and severity of symptoms and emotional distress among responders and nonresponders. Thus, these data provide evidence that elevated serum cortisol and cortisol/DHEA(S) ratios may serve as markers of biological mechanisms that are involved in responsivity of schizophrenia patients to antipsychotic treatment.

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Neurosteroid metabolism in the human brain

Cited by 452 publications

References 121 publications

Inhibitory effects of pharmacological doses of melatonin on aromatase activity and expression in rat glioma cells

Inhibitory effects of pharmacological doses of melatonin on aromatase activity and expression in rat glioma cells

Preclinical effects of melanocortins in male sexual dysfunction

Cortisol/Dehydroepiandrosterone Ratio and Responses to Antipsychotic Treatment in Schizophrenia

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