Distribution and ontogeny of 3α-hydroxysteroid dehydrogenase in the rat brain

Cheng, Kui; Lee, Julie; Khanna, Marilyn; Qin, Kenan

doi:10.1016/0960-0760(94)90175-9

Cited by 23 publications

(4 citation statements)

References 22 publications

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“…In accordance with data on 3a-HSD activity in the rat brain, expression of 3a-HSD type 2 mRNA in the human hippocampus did not differ between the sexes (52,66).…”

Section: A-hydroxysteroid Dehydrogenasesupporting

confidence: 90%

Neurosteroid metabolism in the human brain

Stoffel‐Wagner

2001

European Journal of Endocrinology

452

170

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This review summarizes the current knowledge of the biosynthesis of neurosteroids in the human brain, the enzymes mediating these reactions, their localization and the putative effects of neurosteroids. Molecular biological and biochemical studies have now firmly established the presence of the steroidogenic enzymes cytochrome P450 cholesterol side-chain cleavage (P450SCC), aromatase, 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase in human brain. The functions attributed to specific neurosteroids include modulation of gamma-aminobutyric acid A (GABAA), N-methyl-d-aspartate (NMDA), nicotinic, muscarinic, serotonin (5-HT3), kainate, glycine and sigma receptors, neuroprotection and induction of neurite outgrowth, dendritic spines and synaptogenesis. The first clinical investigations in humans produced evidence for an involvement of neuroactive steroids in conditions such as fatigue during pregnancy, premenstrual syndrome, post partum depression, catamenial epilepsy, depressive disorders and dementia disorders. Better knowledge of the biochemical pathways of neurosteroidogenesis and their actions on the brain seems to open new perspectives in the understanding of the physiology of the human brain as well as in the pharmacological treatment of its disturbances.

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“…In accordance with data on 3a-HSD activity in the rat brain, expression of 3a-HSD type 2 mRNA in the human hippocampus did not differ between the sexes (52,66).…”

Section: A-hydroxysteroid Dehydrogenasesupporting

confidence: 90%

Neurosteroid metabolism in the human brain

Stoffel‐Wagner

2001

European Journal of Endocrinology

452

170

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“…This finding is in accordance with a previous data on 3a-HSOR activity in rat brain ( 4 1 ) . Furthermore, the animal study revealed no sex difference concerning the enzyme activity in brain, that deprivation of steroid hormones by adrenalectomy did not affect expression levels of 3a-HSOR in the brain and that administration of various sex hormones did not affect the enzyme activity (41). In contrast, other authors reported sex differences in local concentrations of 5a-DHP and 3a,5a-THP in the brain (2,42).…”

Section: -Reductase and 3a-hsor In The Hippocampusmentioning

confidence: 51%

Expression of 5α‐Reductase and 3α‐Hydroxisteroid Oxidoreductase in the Hippocampus of Patients with Chronic Temporal Lobe Epilepsy

et al. 2000

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Summary: Purpose:The hippocampus is one of the principal target areas for neurosteroidal action, and the major neuroendocrine conversion of progesterone appears to be Sa-reduction and 301-hydroxysteroid oxidoreduction, leading to the potent neurosteroid 3~~,5~~-tetrahydroxyprogesterone. To investigate whether the human hippocampus is equipped with the enzymes 5a-reductase and 3a-hydroxysteroid oxidoreductase (301-HSOR), we studied the expression of 5a-reductase types 1 and 2 and 3a-HSOR types 1 and 2 in the resected hippocampi of patients with medically intractable chronic temporal lobe epilepsy.Methods: We studied tissue specimens from the hippocampi of 13 women, 25 men, and four children. Quantification of different mRNAs was achieved by competitive reverse transcription-polymerase chain reaction (RT-PCR).Results: Sa-Reductase 1 mRNA and 301-HSOR 2 mRNA were expressed in hippocampi of children and adults, whereas 5a-reductase 2 mRNA and 3a-HSOR 1 mRNA were not expressed. Neither Sa-reductase 1 mRNA nor 3a-HSOR 2 mRNA concentrations in hippocampal tissue showed any statistically significant differences between women and men or between children and adults.Conclusions: This study demonstrates for the first time mRNA expression of the type 1 isozyme of 501-reductase and the type 2 isozyme of 3a-HSOR in the human hippocampus. The finding that both 5a-reductase and 3a-HSOR are present in the hippocampus leads us to assume the synthesis of neuroactive steroids in this human brain area. Key Words: 5a-Reductase-3a-Hydroxysteroid oxidoreductase-Hippocampus-Neurosteroid-Epilepsy .From animal studies, it is known that sex steroid hormones may influence neuronal cerebral excitability, possibly by different modes of action (1,2). Sex steroid hormone metabolism, including aromatization, Sol-reduction and 17P-reduction, and 17P-oxidation has been proven to occur in the human temporal lobe (3-5). The major active products, estrogens and Sol-androstanes are responsible for many behavioral and physiologic effects of the parent steroid (6).Moreover, numerous animal studies have shown that in the central nervous system progesterone is rapidly metabolized to , which is subsequently further reduced to 3qSa-tetraAccepted September 23, 1999. Drs. Stoffel-Wagner and Beyenburg contributed equally to this work.

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“…In addition to the presence of greater levels of precursors in the female brain, differential expression of the 5α‐reductase may contribute to the sex difference, given that expression has been shown to be higher in females, at least in the hippocampus . Moreover, regional differences in expression and activity have been demonstrated for 5α‐reductase and 3α‐HSD in the adult brain, with sexual dimorphic expression being displayed after stress exposure . Any direct effects of DHDOC and DHP are unclear, although DHP is known to have affinity for the progesterone receptor and DHDOC can potentiate GABA‐activated chloride ion currents in neurones, suggesting that, similar to THDOC and allopregnanolone, DHDOC also acts as a positive allosteric modulator at GABA A receptors.…”

Section: Discussionmentioning

confidence: 99%

Sex‐dependent changes in neuroactive steroid concentrations in the rat brain following acute swim stress

Sze

Gill

Brunton

2018

J Neuroendocrinology

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Sex differences in hypothalamic‐pituitary‐adrenal (HPA) axis activity are well established in rodents. In addition to glucocorticoids, stress also stimulates the secretion of progesterone and deoxycorticosterone (DOC) from the adrenal gland. Neuroactive steroid metabolites of these precursors can modulate HPA axis function; however, it is not known whether levels of these steroids differ between male and females following stress. In the present study, we aimed to establish whether neuroactive steroid concentrations in the brain display sex‐ and/or region‐specific differences under basal conditions and following exposure to acute stress. Brains were collected from male and female rats killed under nonstress conditions or following exposure to forced swimming. Liquid chromatography‐mass spectrometry was used to quantify eight steroids: corticosterone, DOC, dihydrodeoxycorticosterone (DHDOC), pregnenolone, progesterone, dihydroprogesterone (DHP), allopregnanolone and testosterone in plasma, and in five brain regions (frontal cortex, hypothalamus, hippocampus, amygdala and brainstem). Corticosterone, DOC and progesterone concentrations were significantly greater in the plasma and brain of both sexes following stress; however, the responses in plasma were greater in females compared to males. This sex difference was also observed in the majority of brain regions for DOC and progesterone but not for corticosterone. Despite observing no stress‐induced changes in circulating concentrations of pregnenolone, DHDOC or DHP, concentrations were significantly greater in the brain and this effect was more pronounced in females than males. Basal plasma and brain concentrations of allopregnanolone were significantly higher in females; moreover, stress had a greater impact on central allopregnanolone concentrations in females. Stress had no effect on circulating or brain concentrations of testosterone in males. These data indicate the existence of sex and regional differences in the generation of neuroactive steroids in the brain following acute stress, especially for the 5α‐reduced steroids, and further suggest a sex‐specific expression of steroidogenic enzymes in the brain. Thus, differential neurosteroidogenesis may contribute to sex differences in HPA axis responses to stress.

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Distribution and ontogeny of 3α-hydroxysteroid dehydrogenase in the rat brain

Cited by 23 publications

References 22 publications

Neurosteroid metabolism in the human brain

Neurosteroid metabolism in the human brain

Expression of 5α‐Reductase and 3α‐Hydroxisteroid Oxidoreductase in the Hippocampus of Patients with Chronic Temporal Lobe Epilepsy

Sex‐dependent changes in neuroactive steroid concentrations in the rat brain following acute swim stress

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