Peripheral nerves: a target for the action of neuroactive steroids

Melcangi, Roberto Cosimo; Cavarretta, Ilaria T.; Ballabio, M.; Leonelli, Emanuela; Schenone, Angelo; Azcoitia, Íñigo; Garcia-Segura, Luis Miguel; Magnaghi, Valerio

doi:10.1016/j.brainresrev.2004.12.021

Cited by 93 publications

(97 citation statements)

References 101 publications

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“…Moreover, overexpression of steroid receptor coactivator (SRC)-1 increased the response of immortalized cell lines of Schwann cells to DHP. In contrast, the effect of this neuroactive steroid was completely lost in the SRC-1-deficient cells [14].…”

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confidence: 88%

“…On the contrary, the effects of THP on protein PMP22 seem to be due to an interaction of this steroid with the GABA-A receptor, whose subunits have been found in Schwann cells [14]. For instance, in primary cultures of Schwann cells the effect of THP on PMP22 is blocked by bicuculline, a classical antagonist of the GABA-A receptors.…”

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confidence: 97%

“…Therefore, an alternative to the use of P, DHP and THP may be the use of molecules that target PR and/or GABA-A receptor [14]. Indeed, Sereda and colleagues have demonstrated that the treatment with an antagonist of PR (i.e., onapristone) is able to reduce the overexpression of PMP22 and to improve CMT phenotype in an experimental model of CMT1A (i.e., PMP22-transgenic rats) [3].…”

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confidence: 99%

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Therapeutic approaches to peripheral neuropathy based on neuroactive steroids

Melcangi

Garcia-Segura

2006

Expert Review of Neurotherapeutics

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confidence: 88%

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confidence: 97%

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confidence: 99%

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Therapeutic approaches to peripheral neuropathy based on neuroactive steroids

Melcangi

Garcia-Segura

2006

Expert Review of Neurotherapeutics

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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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“…Moreover, this steroid regulates the development of some neuronal types (i.e., Purkinje cells of the cerebellum) (Tsutsui et al 2011), oligodendrocytes/Schwann cells (Jung-Testas et al 1996, Ghoumari et al 2005, as well as the myelination process (Chan et al 2000, Melcangi et al 2005, Roglio et al 2008.…”

Section: Introductionmentioning

confidence: 99%

The other side of progestins: effects in the brain

Giatti

Melcangi

Pesaresi

2016

Journal of Molecular Endocrinology

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Progestins are a broad class of progestational agents widely differing in their chemical structures and pharmacological properties. Despite emerging data suggest that progestins, besides their action as endometrial protection, can also have multiple nonreproductive functions, much remains to be discovered regarding the actions exerted by these molecules in the nervous system. Here, we report the role exerted by different progestins, currently used for contraception or in postmenopausal hormone replacement therapies, in regulating cognitive functions as well as social behavior and mood. We provide evidence that the effects and mechanisms underlying their actions are still confusing due to the use of different estrogens and progestins as well as different doses, duration of exposure, route of administration, baseline hormonal status and age of treated women. We also discuss the emerging issue concerning the relevant increase of these substances in the environment, able to deeply affect aquatic wildlife as well as to exert a possible influence in humans, which may be exposed to these compounds via contaminated drinking water and seafood. Finally, we report literature data showing the neurobiological action of progestins and in particular their importance during neurodegenerative events. This is extremely interesting, since some of the progestins currently used in clinical practice exert neuroprotective and anti-inflammatory effects in the nervous system, opening new promising opportunities for the use of these molecules as therapeutic agents for trauma and neurodegenerative disorders.

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Peripheral nerves: a target for the action of neuroactive steroids

Cited by 93 publications

References 101 publications

Therapeutic approaches to peripheral neuropathy based on neuroactive steroids

Therapeutic approaches to peripheral neuropathy based on neuroactive steroids

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

The other side of progestins: effects in the brain

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