Identification of type 1 5α-reductase in myelin membranes of male and female rat brain

Poletti, Angelo; Celotti, F.; Rumio, Cristiano; Rabuffetti, Monica; Martini, L.

doi:10.1016/s0303-7207(97)04056-2

Cited by 57 publications

(38 citation statements)

References 37 publications

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“…By contrast, mature oligodendrocytes have the highest levels of expression of 5α reductase but are unable to convert pregnenolone to progesterone, suggesting a lack of 3ßHSD expression. These data are consistent with previous studies showing expression of 5α reductase activity in oligodendrocyte cultures (Melcangi et al, 1994), and in myelin sheaths (Melcangi et al, 1988;Poletti et al, 1997). The data demonstrating specific oligodendrocyte precursor expression and induction of 3ßHSD further support the hypothesis that progesterone may have an effect during or contribute to oligodendrocyte differentiation.…”

Section: Oligodendrocyte Differentiationsupporting

confidence: 92%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

189

117

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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.

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Section: Oligodendrocyte Differentiationsupporting

confidence: 92%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

189

117

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“…Double-labeling identification with specific markers for neurons, astrocytes, and oligodendrocytes (Raff et al, 1978;Kennedy, 1982;Nagle, 1988;Matus, 1990) revealed that the 5␣-R1 immunostaining (mainly restricted to Wm) was expressed in oligodendrocytes and astrocytes. In agreement with this observation, previous studies have shown that the type 1 isoform of 5␣-R is the most relevant isoenzyme present in myelinated structures of the female and male rat brain (Poletti et al, 1997(Poletti et al, , 1998b. Immunoreactivities for 5␣-R2 and 3␣-HSD were also found in glial cells of the Wm, but a substantial percentage (35%) of the labeling was seen in neurons.…”

Section: ␣-R and 3␣-hsd In The Spinal Cordsupporting

confidence: 86%

Anatomical and cellular localization of neuroactive 5α/3α‐reduced steroid‐synthesizing enzymes in the spinal cord

Patte‐Mensah

Penning

Mensah‐Nyagan

2004

J of Comparative Neurology

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The complementary activities of 5 alpha-reductase (5 alpha-R) and 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) are crucial for the synthesis of neuroactive 5 alpha/3 alpha-reduced steroids, such as 3 alpha-androstanediol, allopregnanolone, and tetrahydrodeoxycorticosterone, which control several important neurophysiological mechanisms through allosteric modulation of gamma-aminobutyric acid type A receptors. Immunocytochemical localization of 3 alpha-HSD in the central nervous system (CNS) has never been determined. The presence and activity of 5 alpha-R have been investigated in the CNS, but only the brain was considered; the spinal cord (SC) received little attention, although this structure is crucial for many sensorimotor activities. We have determined the first cellular distribution of 5 alpha-reductase type 1 (5 alpha-R1) and type 2 (5 alpha-R2) and 3 alpha-HSD immunoreactivities in adult rat SC. 5 alpha-R1 immunostaining was detected mainly in the white matter (Wm). In contrast, intense 5 alpha-R2 labeling was observed in dorsal (DH) and ventral horns of gray matter (Gm). 3 alpha-HSD immunoreactivity was largely distributed in the Wm and Gm, but the highest density was found in sensory areas of the DH. Double-labeling experiments combined with confocal analysis revealed that, in the Wm, 5 alpha-R1 was localized in glial cells, whereas 35% of 5 alpha-R2 and 3 alpha-HSD immunoreactivities were found in neurons. In the DH, 60% of 5 alpha-R2 immunostaining colocalized with oligodendrocyte, 25% with neuron, and 15% with astrocyte markers. Similarly, 45% of 3 alpha-HSD immunoreactivity was found in oligodendrocytes, 35% in neurons, and 20% in astrocytes. These results are the first demonstrating that oligodendrocytes and neurons of the SC possess the key enzymatic complex for synthesizing potent neuroactive steroids that may control spinal sensorimotor processes.

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“…The physiological importance of 5 -reductase (5 -R) (EC 1·3·99·5) in the brain may derive from two of its properties: its capability to convert testosterone (T) to a more potent androgen, dihydrotestosterone (DHT), that appears to participate in the sexual differentiation processes of some brain regions (Lauber & Lichtensteiger 1996, Poletti et al 1997,1998b, Melcangi et al 1998, Torres & Ortega 2003a; and its capability to convert progesterone and deoxycorticosterone (DOC) to their respective 5 -reduced derivatives, precursors of allopregnanolone and tetrahydroDOC, potent allosteric modulators of the -aminobutyric acid receptor (GABA A -R) (Mellon & Griffin 2002), which participates in the regulation of various psychophysiological phenomena (Purdy et al 1991, Majewska 1992, Melcangi et al 2005, Patte-Mensah et al 2005. The enzyme 5 -Reductase (5 -R) (EC 1·3·99·5) exists as two isoforms, 5 -R type 1 (5 -R1) and 5 -R type 2 (5 -R2) and both are present in the brain.…”

Section: Introductionmentioning

confidence: 99%

Steroid 5α-reductase isozymes in the adult female rat brain: central role of dihydrotestosterone

Torres

Ortega

2006

Journal of Molecular Endocrinology

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The enzyme 5 -reductase (5 -R) (EC 1·3·99·5) exists as two isoforms, 5 -R type 1 (5 -R1) and 5 -R type 2 (5 -R2). 5 -R1 has been associated with catabolic functions whereas 5 -R2 has been associated with sexually dimorphic functions of the male. We recently demonstrated that both 5 -R isozymes are present in the central nervous system (CNS) of the adult male rat and are regulated in an opposing way by androgens. This finding raises the question as to whether both isozymes play a role in the sexual dimorphism of the CNS, besides other functions. To test this hypothesis, it is essential to study the regulation of both isozymes by androgens in the female. In this work, we studied the effects of testosterone (T) and dihydrotestosterone (DHT) on mRNA levels of both 5 -R isoforms in the prefrontal cortex of the adult female rat by one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis. Our results demonstrate for the first time that 5 -R2 mRNA is slightly regulated by T and DHT in females. Surprisingly, 5 -R1 mRNA is not regulated by T in the intact female, whereas it is very positively regulated by DHT, a more potent androgen than T. These data indicate the great sexual dimorphism in the CNS with respect to both 5 -R isozymes, and suggest a crucial role of DHT in the sexual dimorphism of the CNS in the female. These results open up a new research line that may lead to a better understanding of the physiology of the CNS.

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Identification of type 1 5α-reductase in myelin membranes of male and female rat brain

Cited by 57 publications

References 37 publications

Neurosteroid regulation of central nervous system development

Neurosteroid regulation of central nervous system development

Anatomical and cellular localization of neuroactive 5α/3α‐reduced steroid‐synthesizing enzymes in the spinal cord

Steroid 5α-reductase isozymes in the adult female rat brain: central role of dihydrotestosterone

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