Need a big favor. S Foote's theory in a nutshell?

[michael barry]

Wook,


That melatonin experiment is even more impressive when one considers that they just used .1% melatonin. We can easily up that ourselves in a homemade topical.

 

[docj077]

In the same cited work:

"Furthermore, androgens affect behavior and cognition."

Armando

Eliminating too much DHT might not be good. There are many people out there complaining of "brain fog" from taking finasteride and dutastreride :x :freaked: :x

That phenomenon is not associated with reduced DHT.

 

[wookster]

In the same cited work:

"Furthermore, androgens affect behavior and cognition."

Armando

Eliminating too much DHT might not be good. There are many people out there complaining of "brain fog" from taking finasteride and dutastreride :x :freaked: :x

That phenomenon is not associated with reduced DHT.

:alien: :ninja: :alien:

http://www.andrologyjournal.org/cgi/con ... l/24/4/568

This study prospectively examined changes in cognition in hypogonadal men given testosterone (T) or older hypogonadal men given dihydrotestosterone (DHT) gel. A battery of cognitive tests assessing verbal and spatial memory, language, and attention was administered at baseline (prior to medication) and again at days 90 and 180 of treatment for men receiving T gel and at baseline and days 30 and 90 of treatment for men receiving DHT gel. For men receiving T gel, circulating total T and estradiol (E2) were significantly raised compared with baseline, and a significant improvement in verbal memory was observed. For men receiving DHT gel, serum DHT levels increased and T levels decreased significantly compared with baseline, and a significant improvement in spatial memory was observed. The results suggest that beneficial changes in cognition can occur in hypogonadal men using T replacement levels and DHT treatment, and these changes in cognition can be reliably measured during a relative steady-state dose level. Further, our results suggest that aromatization of T to E2 may regulate verbal memory in men, whereas nonaromatizable androgens may regulate spatial memory.

 

[wookster]

http://www.hypertrichosis.com/

http://www.hypertrichosis.com/hypertric ... uced.shtml

Drug induced hypertrichosis

Among the more common acquired hypertrichosis types is a class of hypertrichosis caused by drugs. The areas commonly affected by these drugs are the limbs, trunk, back and occasionally the face. The hair growth usually becomes normal after drug intake is stopped.

The drugs that more commonly associated with hypertrichosis include phenytoin, acetazolamide, streptomycin, latanoprost, cyclosporine, psoralen, diazoxide and minoxidil. Of these, phenytoin, cyclosporine and minoxidil are the most frequent causes of generalized hypertrichosis.

 

[docj077]

In the same cited work:

"Furthermore, androgens affect behavior and cognition."

Armando

Eliminating too much DHT might not be good. There are many people out there complaining of "brain fog" from taking finasteride and dutastreride :x :freaked: :x

That phenomenon is not associated with reduced DHT.

:alien: :ninja: :alien:

http://www.andrologyjournal.org/cgi/con ... l/24/4/568

This study prospectively examined changes in cognition in hypogonadal men given testosterone (T) or older hypogonadal men given dihydrotestosterone (DHT) gel. A battery of cognitive tests assessing verbal and spatial memory, language, and attention was administered at baseline (prior to medication) and again at days 90 and 180 of treatment for men receiving T gel and at baseline and days 30 and 90 of treatment for men receiving DHT gel. For men receiving T gel, circulating total T and estradiol (E2) were significantly raised compared with baseline, and a significant improvement in verbal memory was observed. For men receiving DHT gel, serum DHT levels increased and T levels decreased significantly compared with baseline, and a significant improvement in spatial memory was observed. The results suggest that beneficial changes in cognition can occur in hypogonadal men using T replacement levels and DHT treatment, and these changes in cognition can be reliably measured during a relative steady-state dose level. Further, our results suggest that aromatization of T to E2 may regulate verbal memory in men, whereas nonaromatizable androgens may regulate spatial memory.

Again with the studies that don't help your cause.

Having testosterone and estrogen as a requirement make sense. However, what you've posted doesn't help your cause if they're elevating one hormone while allowing the other to fall below baseline. You have too many holes in your argument by using studies with too many variables.

I could easily argue that the outcomes are based more upon the ratio of testosterone to estrogen than with anything to do with DHT.

:hairy: :hairy: :hairy:

As far as I know, children and men with 5AR deficiency have no problems with cognition.

 

[wookster]

I could easily argue that the outcomes are based more upon the ratio of testosterone to estrogen than with anything to do with DHT.

:hairy: :hairy: :hairy:

http://www.pslgroup.com/dg/25A926.htm

No Cognition Benefit From Exogenous Testosterone Plus Finasteride: Presented at AGS

Raising hormone levels in older men using exogenous testosterone with the addition of finasteride did not improve cognitive function, according to a study presented here at the American Geriatrics Society 2006 Annual Scientific Meeting (AGS).

Although previous studies have shown that decreasing testosterone levels are associated with memory loss, the evidence for testosterone therapy's role in improving cognition has been much less clear. Only about half of the randomized controlled trials have shown positive effects.

[...]


Overall, men receiving testosterone did not have significantly improved performance and "the addition of finasteride did not help," Dr. Vaughn said.

http://endo.endojournals.org/cgi/conten ... 146/4/2091

In contrast to the inability of E to influence hippocampal structure in males, testosterone, acting through its androgenic metabolite 5-dihydrotestosterone (DHT), has recently been reported to increase dendritic spine synapses in the CA1 region of the male rat hippocampus (22). The spine-promoting effects of DHT are not completely sexually dimorphic because female rats treated with DHT also show a slight, but significant, increase in CA1 spine synapse density (24). Male mice also experience an increase in CA1 hippocampal spine density during puberty, when endogenous testosterone levels rise. This pubertal increase in dendritic spines can be blocked by prepubertal castration (25). The mechanisms through which androgens promote hippocampal synaptic connectivity in males are presently unknown.

It seems to be, that hippocampal synaptic connectivity is helped by, DHT...

:salut: :jumpy: :salut:

 

[michael barry]

Type one alpha five is in the brain.


If Type 2 DHT really was necessary for some certain cognitive function, then things like Revivogen even would not be safe because Revivogen blocks the DHT made in the hair follicles of the scalp. Very little prostate androgen, being bound almost all the time by globulin in the bloodstream, would ever make it to the head.....

 

[wookster]

Type one alpha five is in the brain.


If Type 2 DHT really was necessary for some certain cognitive function, then things like Revivogen even would not be safe because Revivogen blocks the DHT made in the hair follicles of the scalp. Very little prostate androgen, being bound almost all the time by globulin in the bloodstream, would ever make it to the head.....

I recall reading somewhere that the people with 5ar deficiency from the Dominican republic had lower than normal cognitive functioning. It could be BS though. :wink:

 

[Bryan]

I've read several articles and studies on the pseudohermaphrodites, and I don't recall ever seeing anything about that.

 

[docj077]

I could easily argue that the outcomes are based more upon the ratio of testosterone to estrogen than with anything to do with DHT.

:hairy: :hairy: :hairy:

http://www.pslgroup.com/dg/25A926.htm

No Cognition Benefit From Exogenous Testosterone Plus Finasteride: Presented at AGS

Raising hormone levels in older men using exogenous testosterone with the addition of finasteride did not improve cognitive function, according to a study presented here at the American Geriatrics Society 2006 Annual Scientific Meeting (AGS).

Although previous studies have shown that decreasing testosterone levels are associated with memory loss, the evidence for testosterone therapy's role in improving cognition has been much less clear. Only about half of the randomized controlled trials have shown positive effects.

[...]


Overall, men receiving testosterone did not have significantly improved performance and "the addition of finasteride did not help," Dr. Vaughn said.

http://endo.endojournals.org/cgi/conten ... 146/4/2091


[quote:6802c]

In contrast to the inability of E to influence hippocampal structure in males, testosterone, acting through its androgenic metabolite 5-dihydrotestosterone (DHT), has recently been reported to increase dendritic spine synapses in the CA1 region of the male rat hippocampus (22). The spine-promoting effects of DHT are not completely sexually dimorphic because female rats treated with DHT also show a slight, but significant, increase in CA1 spine synapse density (24). Male mice also experience an increase in CA1 hippocampal spine density during puberty, when endogenous testosterone levels rise. This pubertal increase in dendritic spines can be blocked by prepubertal castration (25). The mechanisms through which androgens promote hippocampal synaptic connectivity in males are presently unknown.

It seems to be, that hippocampal synaptic connectivity is helped by, DHT...

:salut: :jumpy: :salut:[/quote:6802c]

Whatever, Chuckles...

Neurobiol Learn Mem. 2007 Jan;87(1):78-85. Epub 2006 Aug 14. Links
Androgens' effects to enhance learning may be mediated in part through actions at estrogen receptor-beta in the hippocampus.Edinger KL, Frye CA.
Department of Psychology, The University at Albany-SUNY, Life Sciences Research Building Rm 1058, 1400 Washington Avenue, Albany, NY 12222, USA.

Testosterone (T) may enhance cognitive performance. However, its mechanisms are not well understood. First, we hypothesized that if T's effects are mediated in part through actions of its 5alpha-reduced metabolites, dihydrotestosterone (DHT) and/or 3alpha-androstanediol (3alpha-diol) in the hippocampus, then T, DHT, and 3alpha-diol-administration directly to the hippocampus should enhance learning and memory in the inhibitory avoidance task. In order to test this hypothesis, gonadectomized (GDX) male rats were administered T, DHT, or 3alpha-diol via intrahippocampal inserts immediately following training in the inhibitory avoidance task. We found that T tended to increase, and DHT and 3alpha-diol significantly increased, performance in the inhibitory avoidance task compared to vehicle-administered GDX rats. Second, we hypothesized that, if androgens' effects are due in part to actions of 3alpha-diol in the hippocampus, then systemic or intrahippocampal administration of 3alpha-diol should significantly enhance cognitive performance of GDX male rats. Third, we hypothesized that, if androgen metabolites can have actions at estrogen receptors (ERs) in the hippocampus, then administration of ER antisense oligonucleotides (AS-ODNs) directly to the hippocampus of GDX, 3alpha-diol replaced, rats would decrease learning in the inhibitory avoidance task. We found that intrahippocampal administration of AS-ODNs for ERbeta, but not ERalpha, significantly decreased learning and memory of 3alpha-diol replaced rats. Together, these findings suggest that T's effects to enhance learning and memory may take place, in part, through actions of its metabolite, 3alpha-diol, at ERbeta in the dorsal hippocampus.


Again, I would argue that it's not DHT causing the response that you posted above. DHT has metabolites, including 5alpha-diol, of its own that regulate the expression of estrogen receptors, and thus, the response to testosterone, as well. Which means that DHT alone is not responsible for any given process. There is a delicate interplay of all nuclear receptors. No single one really acts alone.

I don't understand why you keep oversimplifying these processes. Simple studies demonstrating cognitive differences with the administration of hormones sans their metabolites doesn't help you or anyone else at all.

:roll: :roll: :roll:

 

[wookster]

Again, I would argue that it's not DHT causing the response that you posted above. DHT has metabolites, including 5alpha-diol, of its own that regulate the expression of estrogen receptors, and thus, the response to testosterone, as well. Which means that DHT alone is not responsible for any given process. There is a delicate interplay of all nuclear receptors. No single one really acts alone.

I don't understand why you keep oversimplifying these processes. Simple studies demonstrating cognitive differences with the administration of hormones sans their metabolites doesn't help you or anyone else at all.

:hmmm: :badmood: :whistle:

Obviously, the DHT is needed as a key factor in conjunction with the metabolites. No DHT, no increased metabolic efficiency for the given process. You cannot jargonize your way out of the discussion DocJ077 :wink:

http://en.wikipedia.org/wiki/Metabolite

Metabolome
Metabolome refers to the complete set of small-molecule metabolites (such as metabolic intermediates, hormones and other signalling molecules, and secondary metabolites) to be found within a biological sample, such as a single organism...

[...]

Metabolites
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in the normal growth, development, and reproduction. A secondary metabolite is not directly involved in those processes, but usually has important ecological function. Examples include antibiotics and pigments.

http://endo.endojournals.org/cgi/conten ... 148/7/3371

Estrogen Receptor-ß Mediates Dihydrotestosterone-Induced Stimulation of the Arginine Vasopressin Promoter in Neuronal Cells

[...]

Arginine vasopressin (AVP) is a neuropeptide involved in the regulation of fluid balance, stress, circadian rhythms, and social behaviors. In the brain, AVP is tightly regulated by gonadal steroid hormones in discrete regions with gonadectomy abolishing and testosterone replacement restoring normal AVP expression in adult males. Previous studies demonstrated that 17ß-estradiol, a primary metabolite of testosterone, is responsible for restoring most of the AVP expression in the brain after castration. However, 5-dihydrotestosterone (DHT) has also been shown to play a role in the regulation of AVP expression, thus implicating the involvement of both androgen and estrogen receptors (ER). Furthermore, DHT, through its conversion to 5-androstane-3ß,17ß-diol, has been shown to modulate estrogen response element-mediated promoter activity through an ER pathway. The present study addressed two central hypotheses: 1) that androgens directly modulate AVP promoter activity and 2) the effect is mediated by an estrogen or androgen receptor pathway. To that end, we overexpressed androgen receptor, ERß, and ERß splice variants in a neuronal cell line and measured AVP promoter activity using a firefly luciferase reporter assay. Our results demonstrate that DHT and its metabolite 5-androstane-3ß,17ß-diol stimulate AVP promoter activity through ERß in a neuronal cell line.

 

[wookster]

http://www.garfield.library.upenn.edu/h ... /1097.html

Journal MOLECULAR AND CELLULAR ENDOCRINOLOGY 198(1-2):89-95
Date 2002 DEC 30
Type Article
Address Merck Res Labs, Dept Clin Res Endocrinol & Metab, RY34-A248,126 E Lincoln Ave, Rahway, NJ 07065 USA Merck Res Labs, Dept Clin Res Endocrinol & Metab, Rahway, NJ 07065 USA

Abstract

Androgens have profound effects on scalp and body hair in humans. Scalp hair grows constitutively in the absence of androgens, while body hair growth is dependent on the action of androgens. Androgenetic alopecia, referred to as male pattern hair loss (MPHL) in men and female pattern hair loss (FPHL) in women, is due to the progressive miniaturization of scalp hair. Observations in both eunuchs, who have low levels of testicular androgens, and males with genetic 5alpha-reductase (5alphaR) deficiency, who have low levels of dihydrotestosterone (DHT), implicate DHT as a key androgen in the pathogenesis of MPHL in men. The development of finasteride, a type 2-selective 5alphaR inhibitor, further advanced our understanding of the role of DHT in the pathophysiology of scalp alopecia. Controlled clinical trials with finasteride demonstrated improvements in scalp hair growth in treated men associated with reductions in scalp DHT content, and a trend towards reversal of scalp hair miniaturization was evident by histopathologic evaluation of scalp biopsies. In contrast to its beneficial effects in men, finasteride did not improve hair growth in postmenopausal women with FPHL. Histopathological evaluation of scalp biopsies confirmed that finasteride treatment produced no benefit on scalp hair in these women. These findings suggest that MPHL and FPHL are distinct clinical entities, with disparate pathophysiologies. Studies that elucidate the molecular mechanisms by which androgens regulate hair growth would provide greater understanding of these differences. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

ensativo: ensativo: ensativo:

 

[wookster]

This appears to put another nail in the coffin of Mr. Foote's theory?

From PubMed:

Men with Kennedy disease have a reduced risk of androgenetic alopecia.

Sinclair R, Greenland KJ, Egmond S, Hoedemaker C, Chapman A, Zajac JD.

Department of Dermatology, University of Melbourne Department of Medicine, and Skin and Cancer Foundation, St Vincent's Hospital, Fitzroy 3065, Victoria, Australia.

Background Spinal and bulbar muscular atrophy or Kennedy disease (KD) is an X-linked neurodegenerative disease caused by an expansion of a polymorphic tandem CAG repeat within the androgen receptor (AR) gene on chromosomal locus Xq11-q12. The CAG repeat region encodes a polyglutamine tract that, when expanded to above 40 in number, results in KD, a neurodegenerative disease primarily targeting lower motor neurones. KD is also associated with partial androgen insensitivity due to loss of receptor function. Degree of expansion of this repeat region, located in the first exon, is correlated with age at onset and disease severity. Androgenetic alopecia (Androgenetic Alopecia) is a polygenic trait also associated with functional polymorphism of the AR gene. Objectives To test whether partial loss of function in the AR gene associated with CAG polymorphism reduces the risk of Androgenetic Alopecia in affected men. Methods Members of the Kennedy's Disease Association, an American-based support group, were invited to participate in an online survey to determine the age-related prevalence of Androgenetic Alopecia among men affected by KD. Data from 115 respondents with KD were compared with data from 654 white men of European descent in Maryborough, Australia. Results The mean Androgenetic Alopecia score for men with KD was 1.64 (95% confidence interval, CI 1.41-1.87). The mean score for men in Maryborough was 2.82 (95% CI 2.71-2.93). The difference between the means was highly significant (P < 0.001), indicating thicker hair among the KD cohort. Treating Androgenetic Alopecia score as a continuous variable we found age to be highly significantly related to Androgenetic Alopecia score in men from Maryborough (P < 0.001) but not among men affected by KD (P = 0.90). Conclusions Men with KD have a reduced risk of Androgenetic Alopecia, likely to be due to a functional alteration in the AR caused by the polyglutamine expansion.

 

[Bryan]

How does that put another nail in the coffin of Stephen Foote's theory?

 

[wookster]

How does that put another nail in the coffin of Stephen Foote's theory?

The theory of the androgen receptor's connection to the causative factors of baldness appears to be ...more correct than the poor lymphatic drainage connection.

http://www.physorg.com/news93615944.html

Chang notes that ginger, a family of spices that includes curcumin, is widely used in China as a folk medicine to treat male-pattern baldness. That condition is caused largely by the activity of the androgen receptor, the protein that is central to the action of testosterone and other male hormones. Chang's laboratory, in collaboration with San Diego-based AndroScience Corp., has screened hundreds of compounds for their activity involving the androgen receptor, which is also involved in prostate cancer, acne, and enlarged prostate, as well as Kennedy's disease.

Among the compounds tested is ASC-J9, a synthetic chemical compound that is loosely based on a compound found in curcumin. Significantly, however, ASC-J9 has been chemically modified compared to its natural counterpart to make it much more powerful. Despite the promise it offers for Kennedy's disease, Chang notes that ASC-J9 must be rigorously screened for side effects and effectiveness, through clinical studies in people, before it can be considered as a possible treatment for any disease.

"The compound we are studying has been significantly modified from the original ingredient found in food like curry or ginger," said Chang, a faculty member in the departments of Urology and Pathology and the James P. Wilmot Cancer Center. "It still must be tested in people. We certainly don't want to mislead people to think these foods themselves have any benefit for Kennedy's disease."

 

[Bryan]

How does that put another nail in the coffin of Stephen Foote's theory?

The theory of the androgen receptor's connection to the causative factors of baldness appears to be ...more correct than the poor lymphatic drainage connection.

I don't understand. How do you arrive at THAT conclusion?

Haven't you even been READING Stephen Foote's material for the last several months and years?? He doesn't deny the importance of androgens/androgen receptors in balding (and the value of antiandrogens), it's just that he thinks they affect balding by a different, more indirect route than what the rest of us normal, sane people think. He thinks that androgens (and antiandrogens) influence that "poor lymphatic drainage" that he blames for male pattern baldness. Did you really not understand that, even after THOUSANDS of posts on that subject from Stephen Foote?? :freaked:

 

[docj077]

Again, I would argue that it's not DHT causing the response that you posted above. DHT has metabolites, including 5alpha-diol, of its own that regulate the expression of estrogen receptors, and thus, the response to testosterone, as well. Which means that DHT alone is not responsible for any given process. There is a delicate interplay of all nuclear receptors. No single one really acts alone.

I don't understand why you keep oversimplifying these processes. Simple studies demonstrating cognitive differences with the administration of hormones sans their metabolites doesn't help you or anyone else at all.

:hmmm: :badmood: :whistle:

Obviously, the DHT is needed as a key factor in conjunction with the metabolites. No DHT, no increased metabolic efficiency for the given process. You cannot jargonize your way out of the discussion DocJ077 :wink:

http://en.wikipedia.org/wiki/Metabolite

Actually, DHT is not needed. There is a very interesting interplay of the nuclear receptors and DHT (or its metabolites) aren't necessarily required for that process. You forget that in the absence of DHT production, testosterone is still converted to estrogen and it still acts at its receptors. DHT may differentially regulate estrogen receptor production, but estrogen will maintain their function.

And, actually, I'm quite capable of "jargonizing" may way out of pretty much any given scientific discussion.

As I said before, you're oversimplifying a very complex process.

 

[wookster]

Haven't you even been READING Stephen Foote's material for the last several months and years?? He doesn't deny the importance of androgens/androgen receptors in balding (and the value of antiandrogens), it's just that he thinks they affect balding by a different, more indirect route than what the rest of us normal, sane people think. He thinks that androgens (and antiandrogens) influence that "poor lymphatic drainage" that he blames for male pattern baldness. Did you really not understand that, even after THOUSANDS of posts on that subject from Stephen Foote?? :freaked:

Mr. Foote hardly ever talks about the molecular machinery invovled with the hair follicle itself. If my interpretation is correct, he doesn't deny the "importance" of androgen receptors but since his idea is one of lymphatic stagnation due to the hydraulic differrential existing in beard region and scalp region, the androgen receptors get upregulated as nature's way of maintaining DHT production. According to Foote, DHT has no direct effect on hair follicles with regards to the miniaturization process. DHT is a lymphatic-pump enhancer

http://www.gourmetstylewellness.com/discussions ... c&start=80

I have a question about androgen receptors and the hydraulic theory of baldness:

http://www.ehrs.org/conferenceabstracts ... sawaya.htm

All scalp biopsies from patients obtained 6 months after finasteride treatment revealed intense upregulation of AR expression in comparison to pre-treatment biopsies of the same patient, whereas ERs were not affected, indicating that AR is very sensitive to the affects of 5a-R type II suppression of DHT.

:freaked: :freaked: :freaked:

How does the hydraulic theory of baldness explain this upregulation of androgen receptors due to finasteride and what part do androgen receptors play in the hydraulic/androgenic balding scenario.

It is a good question, and the answer is simple.

My theory also requires that DHT is produced in the dermal tissue. I am suggesting that DHT evolved primarily to increase lymphatic drainage, and that is it's important role as a male hormone.

Any substance that has evolved to increase lymphatic drainage, would have to be largely produced in the outer tissue (the dermis).

Why? Because if such a substance was mainly introduced into lymph vessels towards the core of the body, the increased vessel pumping would restric flow from the outer tissues.

This back pressure effect is what happens in male pattern baldness according to my theory.

The area's of DHT production according to Merck are quote:

"Type I 5 alpha reductase is predominant in the sebaceous glands of most regions of skin, including scalp, and liver. Type I 5 alpha reductase is responsible for approximately one third of circulating DHT.The type II 5 alpha reductase isozyme is primarily found in prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two thirds of circulating DHT."

DHT production largely in the dermis (the biggest organ in the body), ensures an even effect on lymphatic pumping.

The upregulation process in follicles and other DHT producing structures, is natures way of trying to maintain DHT production.

But this dosen't have to mean the physical effect of DHT is designed to happen where it is produced!

Consider this?

If DHT is only going to be used where it is produced, why is there serum DHT?

This is very inefficient, and nature is not normaly so? Also, why is DHT being produced in the liver? What "direct" function is DHT doing there?

The only possible reason for DHT to be produced in the liver, is so it can be released into the circulation for some purpose.

S Foote.

How do follicles become "sensitive" to androgens? There are a few plausible mechanisms.

:hairy: :hairy: :hairy:

 

[wookster]

Actually, DHT is not needed.

I don't trust doctors. Never have, never will

 

[wookster]

http://www3.interscience.wiley.com/cgi- ... 1&SRETRY=0

Research Article
Testosterone and dihydrotestosterone, but not estradiol, enhance survival of new hippocampal neurons in adult male rats
Mark D. Spritzer *, Liisa A.M. Galea
Department of Psychology, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4

email: Mark D. Spritzer (mspritze@middlebury.edu)

*Correspondence to Mark D. Spritzer, Department of Psychology, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4

Funded by:
Canadian Institute for Health Research (CIHR); Grant Number: MOP62929

Keywords
adult neurogenesis • androgen • dentate gyrus • male rats • testosterone


Abstract
Past research suggested that androgens may play a role in the regulation of adult neurogenesis within the dentate gyrus. We tested this hypothesis by manipulating androgen levels in male rats. Castrated or sham castrated male rats were injected with 5-Bromo-2deoxyuridine (BrdU). BrdU-labeled cells in the dentate gryus were visualized and phenotyped (neural or glial) using immunohistochemistry. Castrated males showed a significant decrease in 30-day cell survival within the dentate gyrus but there was no significant change in cell proliferation relative to control males, indicating that androgens positively affect cell survival, but not cell proliferation. To examine the role of testosterone on hippocampal cell survival, males were injected with testosterone s.c. for 30 days starting the day after BrdU injection. Higher doses (0.5 and 1.0 mg/kg) but not a lower dose (0.25 mg/kg) of testosterone resulted in a significant increase in neurogenesis relative to controls. We next tested the role of testosterone's two major metabolites, dihydrotestosterone (DHT), and estradiol, upon neurogenesis. Thirty days of injections of DHT (0.25 and 0.50 mg/kg) but not estradiol (0.010 and 0.020 mg/kg) resulted in a significant increase in hippocampal neurogenesis. These results suggest that testosterone enhances hippocampal neurogenesis via increased cell survival in the dentate gyrus through an androgen-dependent mechanism. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007