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

Manca, Paolo; Caría, M. A.; Blasi, Juan; Martı́n-Satué, Mireia; Mameli, O.

doi:10.1016/j.jchemneu.2012.07.002

Cited by 7 publications

(5 citation statements)

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“…To our knowledge this is the first report showing the expression of CYP17A1 in the human neuroblastoma cell line SH-SY5Y. The current data do not support results from several other studies, reporting no detectable amount of CYP17A1 mRNA in astrocytes (Cascio et al, 2000) and glial cells (Mellon and Deschepper, 1993) or expression of CYP17A1 almost exclusively in the neurons of the adult rat hippocampus (Hojo et al, 2004), frog brain (Do Rego et al, 2007), and cerebellar nuclei of adult male rats (Manca et al, 2012). Our results are similar but not identical to another previous study, reporting expression of CYP17A1 mRNA and formation of the CYP17A1-mediated products DHEA and androstenedione in cultured primary rat astrocytes as well as in neurons (Zwain and Yen, 1999).…”

Section: Discussioncontrasting

confidence: 99%

“…Several metabolic pathways for biosynthesis of different neurosteroids exist in cells of the central nervous system (CNS). However, data indicate that, in line with tissue-specific differences observed in other parts of the body, metabolism varies in different brain cell types (Cascio et al, 2000;Hojo et al, 2004;Manca et al, 2012;Zwain and Yen, 1999).…”

Section: Introductionmentioning

confidence: 68%

“…Several studies have reported expression of CYP17A1 almost exclusively in neurons (Do Rego et al, 2007;Hojo et al, 2004;Manca et al, 2012). In contrast, another study reported expression of CYP17A1 mRNA and enzyme activity mainly in astrocytes (Zwain and Yen, M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 4 1999), whereas yet other authors report undetectable levels of CYP17A1 mRNA in astrocytes (Cascio et al, 2000), or cultures of glial cells (Mellon and Deschepper, 1993).…”

Section: Introductionmentioning

confidence: 99%

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Expression and regulation of CYP17A1 and 3β-hydroxysteroid dehydrogenase in cells of the nervous system: Potential effects of vitamin D on brain steroidogenesis

Emanuelsson

Almokhtar

Wikvall

et al. 2018

Neurochemistry International

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Steroids are reported to have diverse functions in the nervous system. Enzymatic production of steroid hormones has been reported in different cell types, including astrocytes and neurons. However, the information on some of the steroidogenic enzymes involved is insufficient in many respects. Contradictory results have been reported concerning the relative importance of different cell types in the nervous system for expression of CYP17A1 and 3β-hydroxysteroid dehydrogenase (3β-HSD). 3β-HSD is important in all basic steroidogenic pathways and CYP17A1 is required to form sex hormones. In the current investigation we studied the expression of these enzymes in cultured primary rat astrocytes, in neuron-enriched cells from rat cerebral cortex and in human neuroblastoma SH-SY5Y cells, a cell line often used as an in vitro model of neuronal function and differentiation. As part of this study we also examined potential effects on CYP17A1 and 3β-HSD by vitamin D, a compound previously shown to have regulatory effects in steroid hormone-producing cells outside the brain. The results of our study indicate that astrocytes are a major site for expression of 3β-HSD whereas expression of CYP17A1 is found in both astrocytes and neurons. The current data suggest that neurons, contrary to some previous reports, are not involved in 3β-HSD reactions. Previous studies have shown that vitamin D can influence gene expression and hormone production by steroidogenic enzymes in some cells. We found that vitamin D suppressed CYP17A1-mediated activity by 20% in SH-SY5Ycells and astrocytes. Suppression of CYP17A1 mRNA levels was considerably stronger, about 50% in SH-SY5Y cells and 75% in astrocytes. In astrocytes 3β-HSD was also suppressed by vitamin D, about 20% at the enzyme activity level and 60% at the mRNA level. These data suggest that vitamin D-mediated regulation of CYP17A1 and 3β-HSD, particularly on the transcriptional level, may play a role in the nervous system.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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Expression and regulation of CYP17A1 and 3β-hydroxysteroid dehydrogenase in cells of the nervous system: Potential effects of vitamin D on brain steroidogenesis

Emanuelsson

Almokhtar

Wikvall

et al. 2018

Neurochemistry International

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“…Pregnenolone in turn is converted into progesterone through the action of 3β-hydroxysteroid dehydrogenase. Progesterone is then oxidized to dehydroepiandrosterone and androstenedione by 17α-hydroxylase ( Manca et al, 2012 ). Androstenedione is converted to testosterone by 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3), which is expressed almost exclusively in testicular interstitial cells ( Yazawa et al, 2020 ).…”

Section: Overview Of Estrogenmentioning

confidence: 99%

Biofunctional roles of estrogen in coronavirus disease 2019: Beyond a steroid hormone

Wang

Mao²,

Tai³

et al. 2022

Front. Pharmacol.

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The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), epidemic poses a major global public health threat with more than one million daily new infections and hundreds of deaths. To combat this global pandemic, efficient prevention and management strategies are urgently needed. Together with the main characteristics of COVID-19, impaired coagulation with dysfunctions of the immune response in COVID-19 pathophysiology causes high mortality and morbidity. From recent clinical observations, increased expression of specific types of estrogen appears to protect patients from SARS-CoV-2 infection, thereby, reducing mortality. COVID-19 severity is less common in women than in men, particularly in menopausal women. Furthermore, estrogen levels are negatively correlated with COVID-19 severity and mortality. These findings suggest that estrogen plays a protective role in the pathophysiology of COVID-19. In this review, we discuss the potential roles of estrogen in blocking the SARS-CoV-2 from invading alveolar cells and replicating, and summarize the potential mechanisms of anti-inflammation, immune modulation, reactive oxygen species resistance, anti-thrombosis, vascular dilation, and vascular endothelium protection. Finally, the potential therapeutic effects of estrogen against COVID-19 are reviewed. This review provides insights into the role of estrogen and its use as a potential strategy to reduce the mortality associated with COVID-19, and possibly other viral infections and discusses the possible challenges and pertinent questions.

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“…However, at present there is little information about steroidogenesis in the brainstem. An expression of P450sc and 3α-hydroxy, 5α-reduced steroids has been detected in the rat vestibular nuclei and reticular formation suggesting that neurosteroids are involved in the activity of these structures [ 7 ]. The effects of DHEA and its derivatives on GABA-ergic regulation of raphe nuclei serotoninergic neurons may underlie some functional properties e.g.…”

Section: Introductionmentioning

confidence: 99%

Antipsychotics increase steroidogenic enzyme gene expression in the rat brainstem

et al. 2021

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Background Neurosteroids are involved in several important brain functions and have recently been considered novel players in the mechanic actions of neuropsychiatric drugs. There are no reports of murine studies focusing on the effect of chronic neurosteroid treatment in parallel with antipsychotics on key steroidogenic enzyme expression and we therefore focused on steroidogenic enzyme gene expression in the brainstem of rats chronically treated with olanzapine and haloperidol. Methods and results Studies were carried out on adult, male Sprague–Dawley rats which were divided into 3 groups: control and experimental animals treated with olanzapine or haloperidol. Total mRNA was isolated from homogenized brainstem samples for RealTime-PCR to estimate gene expression of related aromatase, 3β-HSD and P450scc. Long-term treatment with the selected antipsychotics was reflected in the modulation of steroidogenic enzyme gene expression in the examined brainstem region; with both olanzapine and haloperidol increasing aromatase, 3β-HSD and P450scc gene expression. Conclusions The present findings shed new light on the pharmacology of antipsychotics and suggest the existence of possible regulatory interplay between neuroleptic action and steroidogenesis at the level of brainstem neuronal centres.

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

Cited by 7 publications

References 61 publications

Expression and regulation of CYP17A1 and 3β-hydroxysteroid dehydrogenase in cells of the nervous system: Potential effects of vitamin D on brain steroidogenesis

Expression and regulation of CYP17A1 and 3β-hydroxysteroid dehydrogenase in cells of the nervous system: Potential effects of vitamin D on brain steroidogenesis

Biofunctional roles of estrogen in coronavirus disease 2019: Beyond a steroid hormone

Antipsychotics increase steroidogenic enzyme gene expression in the rat brainstem

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