GlasgowCelt
Member
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Does anyone have any views on this or counter-active arguments or studies?
http://www.bio.net/bionet/mm/neur-sci/2004-August/058929.html
http://www.bio.net/bionet/mm/neur-sci/2004-August/058929.html
Propecia may contribute to neurodegeneration
- Thread starter GlasgowCelt
- Start date
No, but I do have more fuel to add to the fire.
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Androgen-induced neurite outgrowth is mediated by neuritin in motor neurones
ONLINE http://www.blackwell-synergy.com/doi/fu ... ookieSet=1
PDF: http://www.blackwell-synergy.com/doi/pd ... 04.02836.x
------------------------
Selected bits:
... Androgens are neuroactive compounds which may regulate molecular and cellular events modulating several brain functions. Androgens regulate sexual and aggressive behaviour (Howell and Shalet 2001), memory, cognitive status (Moffat et al. 2002; Naghdi et al. 2003; Yaffe et al. 2003), mood (Seidman 2003) as well as other brain functions. Most of these effects are mediated by the androgen receptor (AR), a ligand-activated transcription factor which belongs to the nuclear steroid receptor superfamily (Lamb et al. 2001; Gelmann 2002) and is highly expressed in a distinct neuronal population of the CNS (McAbee and DonCarlos 1998; Fernandez-Guasti et al. 2000).
... spinal cord motor neurones express a high level of 5?-R 2, similar to those usually found in the prostate (a typical androgen-dependent structure) and several times higher that those normally detectable in the CNS (Poletti et al. 1997a, 2001; Poletti and Martini 1999; Pozzi et al. 2003).
... It clearly appears that both DHT (p < 0.01) and testosterone (p < 0.05) significantly increased the number of phosphorylated neurofilaments of NSC34/mAR; however, DHT was capable of stimulating neurite outgrowth at levels significantly higher than those obtained with its precursor testosterone (p < 0.01).
The effects of testosterone appear to be mediated by its 5?-reduced derivative. In fact, finasteride, a selective 5?-R 2 inhibitor that blocks DHT formation, completely counteracted the trophic effect exerted by testosterone on neurite outgrowth.
This study confirms this idea firstly by demonstrating that DHT regulates neuritin expression and neurite outgrowth more effectively than its precursor testosterone and secondly by demonstrating that the trophic effects of testosterone on neurite elongation can be fully blocked by the use of the selective 5?-R 2 inhibitor finasteride.
... All together the data presented may become relevant to understanding the effects of a particular type of mutation found in the AR of patients affected by a motor neurone disorder known as spinal and bulbar muscular atrophy (SBMA) or Kennedy's disease (Kennedy et al. 1968).
... Similarly, a recent study has indicated that Alzheimer's disease in male patients may be linked with a different mutation in the CAG triplet repeat domain of the AR, along with reduced testosterone levels in blood serum (Lehmann et al. 2004; Okun et al. 2004).
Testosterone levels in the blood have also been implicated in the pathology of Parkinson's disease in male patients (Okun et al. 2004). Some of these symptoms may be alleviated by testosterone replacement therapy (Okun et al. 2002).
... Finally, another motor neurone disease, the sporadic amyotrophic lateral sclerosis, is characterized by a 2 : 1 higher incidence in men compared with women. It has also been shown that free testosterone (but not total testosterone) is significantly decreased in amyotrophic lateral sclerosis patients compared with age-matched controls, suggesting a possible involvement of androgens in the pathophysiology of sporadic amyotrophic lateral sclerosis (Walling 1999).
The involvement of androgens in the control of neuritin expression, described in the present study, and its putative effect as molecular mediator of the androgenic effects on axonal elongation in motor neurones underlines a possible a link with these clinical observations. Observations derived from the study of these pathologies substantiate the argument that AR exerts a trophic effect on motor neurones (Brooks et al. 1997, 1998).
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Androgen-induced neurite outgrowth is mediated by neuritin in motor neurones
ONLINE http://www.blackwell-synergy.com/doi/fu ... ookieSet=1
PDF: http://www.blackwell-synergy.com/doi/pd ... 04.02836.x
------------------------
Selected bits:
... Androgens are neuroactive compounds which may regulate molecular and cellular events modulating several brain functions. Androgens regulate sexual and aggressive behaviour (Howell and Shalet 2001), memory, cognitive status (Moffat et al. 2002; Naghdi et al. 2003; Yaffe et al. 2003), mood (Seidman 2003) as well as other brain functions. Most of these effects are mediated by the androgen receptor (AR), a ligand-activated transcription factor which belongs to the nuclear steroid receptor superfamily (Lamb et al. 2001; Gelmann 2002) and is highly expressed in a distinct neuronal population of the CNS (McAbee and DonCarlos 1998; Fernandez-Guasti et al. 2000).
... spinal cord motor neurones express a high level of 5?-R 2, similar to those usually found in the prostate (a typical androgen-dependent structure) and several times higher that those normally detectable in the CNS (Poletti et al. 1997a, 2001; Poletti and Martini 1999; Pozzi et al. 2003).
... It clearly appears that both DHT (p < 0.01) and testosterone (p < 0.05) significantly increased the number of phosphorylated neurofilaments of NSC34/mAR; however, DHT was capable of stimulating neurite outgrowth at levels significantly higher than those obtained with its precursor testosterone (p < 0.01).
The effects of testosterone appear to be mediated by its 5?-reduced derivative. In fact, finasteride, a selective 5?-R 2 inhibitor that blocks DHT formation, completely counteracted the trophic effect exerted by testosterone on neurite outgrowth.
This study confirms this idea firstly by demonstrating that DHT regulates neuritin expression and neurite outgrowth more effectively than its precursor testosterone and secondly by demonstrating that the trophic effects of testosterone on neurite elongation can be fully blocked by the use of the selective 5?-R 2 inhibitor finasteride.
... All together the data presented may become relevant to understanding the effects of a particular type of mutation found in the AR of patients affected by a motor neurone disorder known as spinal and bulbar muscular atrophy (SBMA) or Kennedy's disease (Kennedy et al. 1968).
... Similarly, a recent study has indicated that Alzheimer's disease in male patients may be linked with a different mutation in the CAG triplet repeat domain of the AR, along with reduced testosterone levels in blood serum (Lehmann et al. 2004; Okun et al. 2004).
Testosterone levels in the blood have also been implicated in the pathology of Parkinson's disease in male patients (Okun et al. 2004). Some of these symptoms may be alleviated by testosterone replacement therapy (Okun et al. 2002).
... Finally, another motor neurone disease, the sporadic amyotrophic lateral sclerosis, is characterized by a 2 : 1 higher incidence in men compared with women. It has also been shown that free testosterone (but not total testosterone) is significantly decreased in amyotrophic lateral sclerosis patients compared with age-matched controls, suggesting a possible involvement of androgens in the pathophysiology of sporadic amyotrophic lateral sclerosis (Walling 1999).
The involvement of androgens in the control of neuritin expression, described in the present study, and its putative effect as molecular mediator of the androgenic effects on axonal elongation in motor neurones underlines a possible a link with these clinical observations. Observations derived from the study of these pathologies substantiate the argument that AR exerts a trophic effect on motor neurones (Brooks et al. 1997, 1998).
Bubka: You don't find all these studies and the fact that SOME people have severe issues on and after this drug a bit alarming, even if it's working fine for you? Had I known all of this prior, I would never have risked it. It was the assurrance of ignorant people like you on this forum claiming it was harmless and the people taking it and complaining about sides were loonies that helped me with my decision to take it. Here I am with physical changes to my dick, gyno, USD 4000 worh of medical bills etc.
People concidering taking it: Research carefully and then make up your own mind, hair loss really is nothing compared the the potential this drug has in fu*king you up..permanently.
People concidering taking it: Research carefully and then make up your own mind, hair loss really is nothing compared the the potential this drug has in fu*king you up..permanently.
bubka
Senior Member
- Reaction score
- 16
Lets to a logical look at this shall we...
Men in there 20's noticing they don't get erections like they used too... boy that does not happen naturally :thumbdown2:
Men in there 20's who are embarrassed of their hair loss, take propecia and also have depression... boy the pills are what caused it :thumbdown2:
Some of the studies have even shown that the placebo group had HIGHER instances of impotency than the finasteride group. As this dutasteride (with finasteride) study showed.
So until you find some study that significantly shows that finasteride causes the phenomena you are experiencing, you CANNOT scientifically make the claim.
Men in there 20's noticing they don't get erections like they used too... boy that does not happen naturally :thumbdown2:
Men in there 20's who are embarrassed of their hair loss, take propecia and also have depression... boy the pills are what caused it :thumbdown2:
Some of the studies have even shown that the placebo group had HIGHER instances of impotency than the finasteride group. As this dutasteride (with finasteride) study showed.
So until you find some study that significantly shows that finasteride causes the phenomena you are experiencing, you CANNOT scientifically make the claim.
I do understand your point. If you (and most people) have no problems on finasteride, all this must sound weird. If I was in your position, my reaction would probably be similar.
I cannot scientifically prove that finasteride did this, but I was fine prior to this and now have ED, physical changes to my dick and gyno just after four months of finasteride..so that's quite a coincidence. And I can assure you that none of it was psychological, my dick was completely numb to the touch and now has a curve to the left. I was 24 years old and am now 25. The numbness is almost completely gone, but I am nowhere near what I used to be. And the depression was not a normal "depression" that you get for e.g. going bald (my situation wasn't even that bad so it did not get me down), having some kind of complex etc. for me it was more like feeling out of it/not living in the moment..it's hard to explain.
In that study there are 60-70 participants, so that's not a whole lot.
I cannot scientifically prove that finasteride did this, but I was fine prior to this and now have ED, physical changes to my dick and gyno just after four months of finasteride..so that's quite a coincidence. And I can assure you that none of it was psychological, my dick was completely numb to the touch and now has a curve to the left. I was 24 years old and am now 25. The numbness is almost completely gone, but I am nowhere near what I used to be. And the depression was not a normal "depression" that you get for e.g. going bald (my situation wasn't even that bad so it did not get me down), having some kind of complex etc. for me it was more like feeling out of it/not living in the moment..it's hard to explain.
In that study there are 60-70 participants, so that's not a whole lot.
bubka
Senior Member
- Reaction score
- 16
You are correct, that is just one study with dutasteride which is interesting for a number of reasonsttroy said:
However, the 3 or so large N < 1,000 studies have shown side effects to be less than 2%, thus thats why we can say it as fact.
ttroy: is finasteride the only medication you are taking?
TianCross
Member
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- 0
Bubka - without attemtping to sound rude you are either ignorant or completely missing the point. Where do the studies in the first two posts mention side effects concerning libido etc??? They concern themselves with the effect that finasteride might have on neurodegeneration - a perfectly valid question. Try reading a little before you take such a blase attitude towards people sharing information they have picked up.
Furthermore...
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Androgen 5-Alpha-Reductase Type 2 is Highly Expressed and Active in Rat Spinal Cord Motor Neurones
http://www.blackwell-synergy.com/doi/ab ... alCode=jne
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Spinal cord motoneurones express high levels of androgen receptor. However, in responsive tissue, the effects of testosterone is often mediated by the more potent androgenic derivative 5-alpha-dihydrotestosterone (DHT).
This compound is formed in androgen target cells by the enzyme 5-alpha-reductase. Two isoforms of the 5-alpha-reductase, with limited degree of homology, have been cloned, type 1 and type 2.
The low affinity-constitutive type 1 isoenzyme is widely distributed in the body; the high affinity-androgen regulated 5-alpha-reductase type 2 is confined to androgen-dependent structures and shows a peculiar pH optimum at acidic values.
We have previously shown that high levels of 5-alpha-reductase activity are detectable in rat spinal cord. Here, using reverse transcriptase-polymerase chain reaction, we show that both isoforms are expressed in the whole spinal cord of the rat.
The enzymatic pH optimum measured in immortalized spinal cord motoneurones (NSC34) is typical of the type 2 isoenzyme. Using in situ hybridization technique, we found that 5-alpha-reductase type 2 is confined to the motoneuronal cells of the anterior horns of the rat spinal cord, the cells that also are known to express high levels of androgen receptor.
Because of the close association of androgen receptor and 5-alpha alpha-reductase type 2, motoneuronal cells should be considered as target cells for androgens.
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Androgen 5-Alpha-Reductase Type 2 is Highly Expressed and Active in Rat Spinal Cord Motor Neurones
http://www.blackwell-synergy.com/doi/ab ... alCode=jne
-----------------
Spinal cord motoneurones express high levels of androgen receptor. However, in responsive tissue, the effects of testosterone is often mediated by the more potent androgenic derivative 5-alpha-dihydrotestosterone (DHT).
This compound is formed in androgen target cells by the enzyme 5-alpha-reductase. Two isoforms of the 5-alpha-reductase, with limited degree of homology, have been cloned, type 1 and type 2.
The low affinity-constitutive type 1 isoenzyme is widely distributed in the body; the high affinity-androgen regulated 5-alpha-reductase type 2 is confined to androgen-dependent structures and shows a peculiar pH optimum at acidic values.
We have previously shown that high levels of 5-alpha-reductase activity are detectable in rat spinal cord. Here, using reverse transcriptase-polymerase chain reaction, we show that both isoforms are expressed in the whole spinal cord of the rat.
The enzymatic pH optimum measured in immortalized spinal cord motoneurones (NSC34) is typical of the type 2 isoenzyme. Using in situ hybridization technique, we found that 5-alpha-reductase type 2 is confined to the motoneuronal cells of the anterior horns of the rat spinal cord, the cells that also are known to express high levels of androgen receptor.
Because of the close association of androgen receptor and 5-alpha alpha-reductase type 2, motoneuronal cells should be considered as target cells for androgens.
Androgen-activating enzymes in the central nervous system.
http://www.ncbi.nlm.nih.gov/entrez/quer ... s=10418985
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1: J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):117-22.
Androgen-activating enzymes in the central nervous system.Poletti A, Martini L. Istituto di Endocrinologia, Universita di Milano, Milan, Italy.
In the rat brain, several steroids can be converted by specific enzymes to either more potent compounds or to derivatives showing new biological effects.
One of the most studied enzyme is the 5alpha-reductase (5alpha-R), which acts on 3keto-delta4 steroids. In males, testosterone is the main substrate and gives rise to the most potent natural androgen dihydrotestosterone.
In females, progesterone is reduced to dihydroprogesterone, a precursor of allopregnanolone, a natural anxiolytic/anesthetic steroid. Other substrates are some gluco- and minero-corticoids. Two isoforms of the 5alpha-R, with limited degree of homology, have been cloned: 5alpha-R type 1 and type 2.
The 5alpha-R type 1 possesses low affinity for the various substrates and is widely distributed in the body, with the highest levels in the liver; in the brain, this isoform is expressed throughout life and does not appear to be controlled by androgens.
5Alpha-R type 1 in the rat brain is mainly concentrated in myelin membranes, where it might be involved in the catabolism of potentially neurotoxic steroids.
The 5alpha-R type 2 shows high affinity for the various substrates, a peculiar pH optimum at acidic values and is localized in androgen-dependent structures. In the rat brain, the type 2 isoform is expressed at high levels only in the perinatal period and is controlled by androgens, at least in males.
In adulthood, the type 2 gene appears to be specifically expressed in localised brain regions, like the hypothalamus and the hippocampus. The 5alpha-R type 2 is present in the GT1 cells, a model of LHRH-secreting neurons.
These cells also contain the androgen receptor, which is probably involved in the central negative feedback effect exerted by androgens on the hypothalamic-pituitary-gonadal axis.
The physiological significance of these and additional data will be discussed.
------------------
The Regulation of Gonadotropin-Releasing Hormone-Induced Calcium Signals in Male Rat Gonadotrophs by Testosterone Is Mediated by Dihydrotestosterone
Endocrinology Vol. 139, No. 3 1038-1045
http://endo.endojournals.org/cgi/reprint/139/3/1038.pdf
-----------
"... The 5a-reduction of T appears to be a critical step in the regulation of GnRH-induced Ca2+ signals."
"... Finasteride treatment of intact male rats did, however, mimic the effect of castration on GnRH-induced Ca2+ signals."
"...The anterior pituitary and gonadotrophs in particular have very high levels of 5a-reductase activity (37), suggesting that the metabolism of T plays a role in gonadotroph function.
"...The present study, therefore, hints at a possible function of the 5-reductase in the pituitary, viz. the regulation of GnRH-induced Ca2+ signaling."
The effectiveness of finasteride treatment was established by the resulting decrease in the weight of the ventral prostate and in prostatic DHT concentrations, and we assume that a similar inhibition of 5a-reductase activity would be observed in the pituitary, as has been previously reported (35).
"In summary, this study has demonstrated the importance of the conversion of T to DHT in the regulation of GnRH-induced Ca2+ signals in anterior pituitary gonadotrophs. As such, they hint at an important function of the abundant 5-reductase activity found in the anterior pituitary gland."
http://www.ncbi.nlm.nih.gov/entrez/quer ... s=10418985
------------------------------------------------------------------------------
1: J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):117-22.
Androgen-activating enzymes in the central nervous system.Poletti A, Martini L. Istituto di Endocrinologia, Universita di Milano, Milan, Italy.
In the rat brain, several steroids can be converted by specific enzymes to either more potent compounds or to derivatives showing new biological effects.
One of the most studied enzyme is the 5alpha-reductase (5alpha-R), which acts on 3keto-delta4 steroids. In males, testosterone is the main substrate and gives rise to the most potent natural androgen dihydrotestosterone.
In females, progesterone is reduced to dihydroprogesterone, a precursor of allopregnanolone, a natural anxiolytic/anesthetic steroid. Other substrates are some gluco- and minero-corticoids. Two isoforms of the 5alpha-R, with limited degree of homology, have been cloned: 5alpha-R type 1 and type 2.
The 5alpha-R type 1 possesses low affinity for the various substrates and is widely distributed in the body, with the highest levels in the liver; in the brain, this isoform is expressed throughout life and does not appear to be controlled by androgens.
5Alpha-R type 1 in the rat brain is mainly concentrated in myelin membranes, where it might be involved in the catabolism of potentially neurotoxic steroids.
The 5alpha-R type 2 shows high affinity for the various substrates, a peculiar pH optimum at acidic values and is localized in androgen-dependent structures. In the rat brain, the type 2 isoform is expressed at high levels only in the perinatal period and is controlled by androgens, at least in males.
In adulthood, the type 2 gene appears to be specifically expressed in localised brain regions, like the hypothalamus and the hippocampus. The 5alpha-R type 2 is present in the GT1 cells, a model of LHRH-secreting neurons.
These cells also contain the androgen receptor, which is probably involved in the central negative feedback effect exerted by androgens on the hypothalamic-pituitary-gonadal axis.
The physiological significance of these and additional data will be discussed.
------------------
The Regulation of Gonadotropin-Releasing Hormone-Induced Calcium Signals in Male Rat Gonadotrophs by Testosterone Is Mediated by Dihydrotestosterone
Endocrinology Vol. 139, No. 3 1038-1045
http://endo.endojournals.org/cgi/reprint/139/3/1038.pdf
-----------
"... The 5a-reduction of T appears to be a critical step in the regulation of GnRH-induced Ca2+ signals."
"... Finasteride treatment of intact male rats did, however, mimic the effect of castration on GnRH-induced Ca2+ signals."
"...The anterior pituitary and gonadotrophs in particular have very high levels of 5a-reductase activity (37), suggesting that the metabolism of T plays a role in gonadotroph function.
"...The present study, therefore, hints at a possible function of the 5-reductase in the pituitary, viz. the regulation of GnRH-induced Ca2+ signaling."
The effectiveness of finasteride treatment was established by the resulting decrease in the weight of the ventral prostate and in prostatic DHT concentrations, and we assume that a similar inhibition of 5a-reductase activity would be observed in the pituitary, as has been previously reported (35).
"In summary, this study has demonstrated the importance of the conversion of T to DHT in the regulation of GnRH-induced Ca2+ signals in anterior pituitary gonadotrophs. As such, they hint at an important function of the abundant 5-reductase activity found in the anterior pituitary gland."
jakeb
Established Member
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- 0
I've been off Finasteride for a year and while I did improve when I quit, I'm STILL not 100%.
I'm as skeptical as they come and I have every reason to not believe it's bad for me... since I quit, my hair has been falling out like no tomorrow. But still, there's no way I'd go back.
I'm as skeptical as they come and I have every reason to not believe it's bad for me... since I quit, my hair has been falling out like no tomorrow. But still, there's no way I'd go back.
I did take painkillers called Arcoxia (cox-2 inhibitor) for joint pain but that's it. Have been taking it for years without issues. And the problem is i haven't been taking finasteride for over seven months and these sides are still present! Otherwise I would not complain about sides, but s*it really hit the fan right after quitting it. I have posted this before.bubka said:
edit: Oh and only about a month or so ago did my brain "clear up" 100%. I can assure you it's a great feeling.
TianCross said:
It just made me feel super-anxious and emotionally flat. Did not feel like "myself". Even my family noticed that I was extremely distant, quiet and "occupied". It was not like normal moodiness or depression, a really weird feeling.
Here is my post from july when I was still on finasteride, this was a month or two before I quit and all those devastating things started to happen viewtopic.php?f=43&t=39260
And to who ever mentioned depression or anxiety being caused by hairloss, as finasteride is the final attempt to keep one's hair, I think most people try to believe in it and deny sides as long as possible in order to keep taking it, so the sides must be extremely apparent to make one stop taking it..
R U GOING BALD
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bubka
Now you see proof about side effects and your still f*****g clueless and ignorant!
Now you see proof about side effects and your still f*****g clueless and ignorant!
http://www.sciencedirect.com/science?_o ... 9dab414535
Possible involvement of 5?-reduced neurosteroids in adrenergic and serotonergic stimulation of GFAP gene expression in rat C6 glioma cells
Kyoji Moritaa, , , Hideki Arimochib, Hiroyuki Itoha and Song Herc, 1
aDepartment of Pharmacology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan
bDepartment of Molecular Bacteriology, Tokushima University School of Medicine, Kuramoto, Tokushima 770-8503, Japan
cDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5485, USA
Accepted 7 February 2006. Available online 3 April 2006.
Abstract
Influence of adrenergic and serotonergic stimulation on glial fibrillary acidic protein (GFAP) gene expression in rat C6 glioma cells was first examined as an in vitro model experiment for investigating the neuronal regulation of glial cell differentiation. Stimulation of these cells with isoproterenol and serotonin elevated GFAP mRNA levels followed by an increase in its protein contents, thus suggesting that both adrenergic and serotonergic stimulation might induce the differentiation of the glioma cells. In addition, progesterone and its 5?-reduced metabolite dihydroprogesterone also elevated GFAP mRNA levels in rat C6 glioma cells, consistent with their stimulatory actions on GFAP gene expression observed in rat astrocytes (Melcangi, R.C., Riva, M.A., Fumagalli, F., Magnaghi, V., Racagni, G., Martini, L., 1996. Effect of progesterone, testosterone and their 5?-reduced metabolites on GFAP gene expression in type 1 astrocytes, Brain Res. 711, 10–15). Further studies showed that the elevation of GFAP mRNA levels induced by isoproterenol and serotonin as well as progesterone was abolished by pretreatment of the glioma cells with finasteride, an inhibitor of 5?-reduced steroid production. Moreover, the stimulatory actions of isoproterenol and serotonin on GFAP gene expression were inhibited by pretreatment with a GABAA receptor antagonist bicuculline and a progesterone receptor antagonist RU486. These findings suggest that both adrenergic and serotonergic stimulation may indirectly activate GFAP gene expression probably through the production of 5?-reduced steroid metabolites in rat C6 glioma cells, proposing the possibility that 5?-reduced neurosteroids may play a potential role in the neuronal regulation of glial cell differentiation.
Possible involvement of 5?-reduced neurosteroids in adrenergic and serotonergic stimulation of GFAP gene expression in rat C6 glioma cells
Kyoji Moritaa, , , Hideki Arimochib, Hiroyuki Itoha and Song Herc, 1
aDepartment of Pharmacology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan
bDepartment of Molecular Bacteriology, Tokushima University School of Medicine, Kuramoto, Tokushima 770-8503, Japan
cDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5485, USA
Accepted 7 February 2006. Available online 3 April 2006.
Abstract
Influence of adrenergic and serotonergic stimulation on glial fibrillary acidic protein (GFAP) gene expression in rat C6 glioma cells was first examined as an in vitro model experiment for investigating the neuronal regulation of glial cell differentiation. Stimulation of these cells with isoproterenol and serotonin elevated GFAP mRNA levels followed by an increase in its protein contents, thus suggesting that both adrenergic and serotonergic stimulation might induce the differentiation of the glioma cells. In addition, progesterone and its 5?-reduced metabolite dihydroprogesterone also elevated GFAP mRNA levels in rat C6 glioma cells, consistent with their stimulatory actions on GFAP gene expression observed in rat astrocytes (Melcangi, R.C., Riva, M.A., Fumagalli, F., Magnaghi, V., Racagni, G., Martini, L., 1996. Effect of progesterone, testosterone and their 5?-reduced metabolites on GFAP gene expression in type 1 astrocytes, Brain Res. 711, 10–15). Further studies showed that the elevation of GFAP mRNA levels induced by isoproterenol and serotonin as well as progesterone was abolished by pretreatment of the glioma cells with finasteride, an inhibitor of 5?-reduced steroid production. Moreover, the stimulatory actions of isoproterenol and serotonin on GFAP gene expression were inhibited by pretreatment with a GABAA receptor antagonist bicuculline and a progesterone receptor antagonist RU486. These findings suggest that both adrenergic and serotonergic stimulation may indirectly activate GFAP gene expression probably through the production of 5?-reduced steroid metabolites in rat C6 glioma cells, proposing the possibility that 5?-reduced neurosteroids may play a potential role in the neuronal regulation of glial cell differentiation.