Immunohistochemical presence of 5 α-reductase rat type I -containing cells in the rat brain

Tsuruo, Yoshihiro; Miyamoto, Tadayuki; Yokoi, Hiromichi; Kitagawa, Kouki; Futaki, Shiroh; Ishimura, Kazunori

doi:10.1016/0006-8993(96)00188-6

Cited by 24 publications

(25 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, in multiple regions throughout the rodent brain, 5α reductase and 3α HSD co-localize in the same neurons, and these neurons are both glutamatergic and GABA-ergic. These data confirm those found for expression of 5α reductase in neurons (Melcangi et al, 1994), but differ from earlier observations of its expression in glia (Tsuruo et al, 1996) or from data suggesting lack of neuronal expression of 3α HSD (Melcangi et al, 1994). Nevertheless, the data suggest that these two neurosteroidogenic enzymes are highly expressed in output neurons, glutamatergic pyramidal, GABA-ergic reticulothalamic, striatal and Purkinje neurons, are absent in GABA-interneurons in the telencephalon or hippocampus, and are present to a lesser extent in glutamatergic granular interneurons in the cerebellum and GABA-ergic granular cells in the olfactory bulb.…”

Section: General Overviewsupporting

confidence: 65%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

189

117

View full text Add to dashboard Cite

Neurosteroids are a relatively new class of neuroactive compounds, brought to prominence in the past two decades. Despite knowing of their presence in the nervous system of various species for over twenty years and knowing of their functions as GABA A and NMDA ligands, new and unexpected functions of these compounds are continuously being identified. Absence or reduced concentrations of neurosteroids during development and in adults may be associated with neurodevelopmental, psychiatric, or behavioral disorders. Treatment with physiologic or pharmacologic concentrations of these compounds may also promote neurogenesis, neuronal survival, myelination, increased memory, and reduced neurotoxicity. This review highlights what is currently known about the neurodevelopmental functions and mechanisms of action of four distinct neurosteroids -pregnenolone, progesterone, allopregnanolone and dehydroepiandrosterone.

show abstract

Section: General Overviewsupporting

confidence: 65%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

189

117

View full text Add to dashboard Cite

show abstract

“…Our studies, however, differ from the preceding immunohistochemical studies conducted with 5␣-R type I antibodies (30,31,35) in rat brains. In fact, using a specific 5␣-R type I antibody (see Fig.…”

Section: Discussioncontrasting

confidence: 53%

“…However, in the adult rat brain, 5␣-R type I immunoreactivity is expressed primarily by glial cells that also express S100␤ (30,31). Hence, it is not clear whether 5␣-R type I is selectively expressed in the neurons of the adult rodent brain and whether it coexists with 3␣-HSD.…”

mentioning

confidence: 88%

Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis

Agís‐Balboa

Pinna

Zhubi

et al. 2006

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

352

328

View full text Add to dashboard Cite

Allopregnanolone (ALLO) and tetrahydrodeoxycorticosterone (THDOC) are potent positive allosteric modulators of GABA action at GABAA receptors. ALLO and THDOC are synthesized in the brain from progesterone or deoxycorticosterone, respectively, by the sequential action of two enzymes: 5␣-reductase (5␣-R) type I and 3␣-hydroxysteroid dehydrogenase (3␣-HSD). This study evaluates 5␣-R type I and 3␣-HSD mRNA expression level in mouse brain by using in situ hybridization combined with glutamic acid decarboxylase 67͞65, vesicular glutamate transporter 2, glial fibrillary acidic protein, and S100␤ immunohistochemistry. We demonstrate that 5␣-R type I and 3␣-HSD colocalize in cortical, hippocampal, and olfactory bulb glutamatergic principal neurons and in some output neurons of the amygdala and thalamus. Neither 5␣-R type I nor 3␣-HSD mRNAs are expressed in S100␤-or glial fibrillary acidic protein-positive glial cells. Using glutamic acid decarboxylase 67͞65 antibodies to mark GABAergic neurons, we failed to detect 5␣-R type I and 3␣-HSD in cortical and hippocampal GABAergic interneurons. However, 5␣-R type I and 3␣-HSD are significantly expressed in principal GABAergic output neurons, such as striatal medium spiny, reticular thalamic nucleus, and cerebellar Purkinje neurons. A similar distribution and cellular location of neurosteroidogenic enzymes was observed in rat brain. Taken together, these data suggest that ALLO and THDOC, which can be synthesized in principal output neurons, modulate GABA action at GABAA receptors, either with an autocrine or a paracrine mechanism or by reaching GABAA receptor intracellular sites through lateral membrane diffusion.3␣-hydroxysteroid dehydrogenase ͉ 5␣-reductase (type I) ͉ GABAergic neurons ͉ glutamatergic neurons T he neurosteroids 3␣-hydroxy-5␣-pregnan-20-one [allopregnanolone (ALLO)] and 3␣,21-dihydroxy-5␣-pregnan-20-one [tetrahydrodeoxycorticosterone (THDOC)] are potent positive allosteric modulators of GABA action at GABA A receptors (1-6). These neurosteroids can be synthesized in the brain from progesterone (7) or deoxycorticosterone (8, 9), respectively, by the sequential action of two enzymes, 5␣-reductase (5␣-R) type I and 3␣-hydroxysteroid dehydrogenase (3␣-HSD) (10).Two types (I and II) of 5␣-Rs, which convert progesterone into 5␣-dihydroprogesterone (5␣-DHP) or convert deoxycorticosterone into 5␣-dihydrodeoxycorticosterone (5␣-DHDOC), have been identified in tissues of rodents and humans (11). Whereas 5␣-R type I and II are abundantly expressed in several peripheral tissues, 5␣-R type I is the most abundant 5␣-R molecular form detected in the adult brains of rats, mice, and humans (11-17). The human brain expresses four types of 3␣-HSD, which, under different optimal conditions, either catalyze the reduction of 5␣-DHP into ALLO or reverse this reaction (18). So far, only one 3␣-HSD isoform has been identified in the rat or mouse brain (19)(20)(21)(22). The mRNA sequences of 5␣-R type I (Ϸ88%) and 3␣-HSD (Ϸ89%) are highly homologous in mouse (5␣-R type I GeneBank access...

show abstract

“…In adult male rats the 5␣-reduced metabolites DHT and dihydroprogesterone increase gene expression of myelin-specific proteins in the sciatic nerve and cultured Schwann cells (Magnaghi et al, 1999; see also Melcangi et al, 2000). Also, immunohistochemistry indicates that 5␣-reductase is preferentially located in white matter of the adult rat brain (Tsuruo et al, 1996), and assays of enzyme activity reveal 5␣-reductase in glial cells, including cultured astrocytes and oligodendrocytes from fetal and neonatal rat brain (Melcangi et al, 1993) FIG. 1.…”

Section: Discussionmentioning

confidence: 96%