The 5α-reductase in the central nervous system: expression and modes of control

Melcangi, Roberto Cosimo; Poletti, Angelo; Cavarretta, Ilaria T.; Celotti, F.; Colciago, Alessandra; Magnaghi, Valerio; Motta, Marcella; Negri‐Cesi, P.; Martini, L.

doi:10.1016/s0960-0760(98)00030-2

Cited by 115 publications

(57 citation statements)

References 25 publications

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“…It has been suggested that these enzymes play different roles in mammals: 5 ␣ R1 may serve to catabolize excess T, whereas 5 ␣ R2 may be important for sexual differentiation and male-specific behaviors [Melcangi et al, 1998]. Because it is not expressed as prevalently in the lizard brain, it is possible that 5 ␣ R1 was co-opted for clearing excess androgen from the brain later in evolution.…”

Section: Discussionmentioning

confidence: 99%

Distribution of Two Isozymes of 5α-Reductase in the Brains of Adult Male and Female Green Anole Lizards

Cohen

Wade²

2010

Brain Behav Evol

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The 5α-reductase (5αR) enzyme converts testosterone to 5α-dihydrotestosterone. This local metabolism within the brain is important for the full expression of male sexual behavior in many species, including green anole lizards. Two isozymes of 5αR exist and little is known about their specific distributions. We conducted in situ hybridization for both isozymes in intact male and female green anole brains during the breeding (BS) and non-breeding (NBS) seasons. 5αR1 mRNA was only detected in the brainstem, while 5αR2 was expressed in specific areas throughout the brain. As our primary interest was evaluating the potential role of 5αR in forebrain regulation of reproductive behavior, we quantified 5αR2 expression in the preoptic area, amygdala (AMY), and ventromedial hypothalamus (VMH). More 5αR2 cells were detected during the NBS than BS in the AMY, and the density of these cells was greater in females than males. In the VMH, the right side contained more 5αR2 cells than the left, an effect driven by a lateralized increase in the NBS. These data expand understanding of the distribution and potential roles of both isozymes in the adult brain, and differences in expression patterns between mammals and birds suggest that they may have been co-opted for different functions later in evolution.

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Section: Discussionmentioning

confidence: 99%

Distribution of Two Isozymes of 5α-Reductase in the Brains of Adult Male and Female Green Anole Lizards

Cohen

Wade²

2010

Brain Behav Evol

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“…In summary, a relatively long time might be required to reach this threshold, but once it is reached, the modulation of mIPSC kinetics might reflect the actual speed of production of neurosteroids. Because the expression of 5␣-reductase appears to be stable throughout postnatal development (Melcangi et al, 1998;Compagnone and Mellon, 2000;Lephart et al, 2001), the observed developmental changes in tonic neurosteroidogenesis are likely to involve a plastic mechanism upstream of 5␣-reductase possibly in relation with the expression of PBR and/or of its endogenous ligands and/or a downregulation of the activity of 5␣-reductase in the adult.…”

Section: Discussionmentioning

confidence: 99%

Production of 5α-Reduced Neurosteroids Is Developmentally Regulated and Shapes GABA_AMiniature IPSCs in Lamina II of the Spinal Cord

Keller

Breton²,

Schlichter³

et al. 2004

J. Neurosci.

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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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The 5α-reductase in the central nervous system: expression and modes of control

Cited by 115 publications

References 25 publications

Distribution of Two Isozymes of 5α-Reductase in the Brains of Adult Male and Female Green Anole Lizards

Distribution of Two Isozymes of 5α-Reductase in the Brains of Adult Male and Female Green Anole Lizards

Production of 5α-Reduced Neurosteroids Is Developmentally Regulated and Shapes GABA_AMiniature IPSCs in Lamina II of the Spinal Cord

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

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The 5α-reductase in the central nervous system: expression and modes of control

Cited by 115 publications

References 25 publications

Distribution of Two Isozymes of 5α-Reductase in the Brains of Adult Male and Female Green Anole Lizards

Distribution of Two Isozymes of 5α-Reductase in the Brains of Adult Male and Female Green Anole Lizards

Production of 5α-Reduced Neurosteroids Is Developmentally Regulated and Shapes GABAAMiniature IPSCs in Lamina II of the Spinal Cord

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

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Production of 5α-Reduced Neurosteroids Is Developmentally Regulated and Shapes GABA_AMiniature IPSCs in Lamina II of the Spinal Cord