For Harold, about dowregulating androgen dependent gene exp.

[michael barry]

Harold,

In regards to genistein, look at this:

http://www.pubmedcentral.nih.gov/articl ... gure&id=F4


Am I reading that right? It appears that downstream of cultivation with androgens, almost nada happens with these cells when genistein is added, but we know genistein doesn't block receptors (but it does downregulate androgen-receptor expression, which is well-known scientifically now as the following link demonstrates: (http://linkinghub.elsevier.com/retrieve ... 3803004688)



It appears some genes dont get expressed despite of androgenic uptake in the presence of genistein: http://www.ars.usda.gov/research/public ... 115=168447

[Expression of androgen- and estrogen-regulated genes was measured in LNCaP cells cultured in the presence or absence of hormonal stimulation and the presence or absence of genistein. Genistein strongly suppressed basal expression of androgen-responsive gene (ARG) mRNAs, including prostate specific antigen (PSA) and Ste20-related proline-alanine rich kinase (SPAK), in LNCaP cells grown in 10% FBS. However, genistein had little or no effect on basal expression of two other ARGs beta2-microglobulin (B2M) or selenoprotein P (SEPP1) mRNA under similar cell growth conditions. Culturing LNCaP cells in the presence of the synthetic androgen R1881 induced increases in PSA, SPAK, B2M and SEPP1 mRNAs. The R1881-induced expression of these genes was uniformly blocked by genistein. For PSA and SPAK, genistein also blocked or down-regulated 17beta-estradiol-induced increases in mRNA expression. These results indicate that genistein selectively alters expression of ARG mRNAs in LNCaP cells through modulation of both androgen- and estrogen-induced signaling pathway. Based on these results, we proposed that the regulation of androgen receptor- as well as estrogen receptor-mediated events is potentially relevant chemopreventive mechanism for genistein administered at physiologic levels. /quote]




Harold,
If I remember right, the whole cell assay inhibition of alpha five reductase by genistein was 22% for type one and 89% for type two (Im certain about the later). Genistein has been shown to NOT BLOCK the androgen receptor in experiments (I have links for that), but the downstream gene activity, according the the first graph (the first link in this post) seem to demonstrate that genistein inhibits more downstream androgenic-stimulated gene activity than hydroxyflutamide or RU58841. The USDA article seems to indicate things downstream of androgen uptake that should be happening simply dont in the presence of genistein......................................maybe this is an explanation why sebum levels are so drastically reduced by topical soy in those rats and on people's faces despite the fact that genistein and daidzien are supposedly only "so-so" alpha five reductase type one inhibitiors?



One more thingy...........................and this IS interesting, Apparently neo-natal exposure to genistein lessens the expression of both androgen and estrogen receptors to the baby mice when born:

[quote:3lzlu3jb]Neonatal exposure to genistein reduces expression of estrogen receptor alpha and androgen receptor in testes of adult mice.Shibayama T, Fukata H, Sakurai K, Adachi T, Komiyama M, Iguchi T, Mori C.
Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama.

We investigated the long-term estrogenic influence of genistein on the male reproductive system in mice. Newborn ICR male mice were treated with genistein (10, 100, or 1,000 microg/mouse) for neonatal 5 days. As positive control, administration of diethylstilbestrol (0.5-50 microg/mouse) was carried out. In mice exposed to genistein,we examined weight of testes, sperm counts, sperm motility, and mRNA expression levels of estrogen receptor a (ERalpha) and androgen receptor (AR) at 4, 8 or 12 weeks after birth. Moreover, at 12 weeks of age, we evaluated protein level of ERalpha. In our conventional reproductive-toxicological study (weight of testes, sperm counts and sperm motility), neonatal transient exposure to genistein did not show adverse effects on the male reproductive system in 4, 8 or 12 week old mice. However, in mice treated with genistein mRNA expression levels of ERa and AR were reduced at 8 weeks. This reduction was recovered at 12 weeks in mice treated with a lower dose (10 microg) of genistein but not in those with higher doses (100 microg and 1,000 microg). In addition, ERa protein levels tended to decrease in 12 weeks of adulthood. Our results exhibited that the disruption of gene expression continued for long term such as 3 months after administration of genistein, even if no effect was found at conventional reproductive-toxicological level. We have shown that neonatal administration of weak estrogenic compound (genistein) affects male reproductive organs at molecular levels in adulthood.

[/quote:3lzlu3jb]



Perhaps this is why Asian men born in Asia who still eat the traditional soy-heavy diet have little body hair, but nice head hair..................and comparitively little acne? Do they have less androgen receptor expression PERIOD due to both eating soya but somewhat less intense androgen receptor expression due to their mothers eating soy?






Parting shot: On male pattern baldness-research, (I dont like that site much either), they DID note that experiments with high fat diets dont indicate the hairloss effect that researchers expected, and that its been suggested that the fact that SOY is eaten a great deal in the east might be the reason that Asians with the traditional diet still have nice hair vs. urban Asians whose hair isn't as good as it was sixty years ago (and now have more acne in adolescence). Internal soy isoflavone only decreases serum DHT by something like 15 percent though........................perhaps topical soy isoflavones might be very very effective in male pattern baldness?

Any thoughts? Am I reading this 'wrong'?

 

[harold]

Harold,

In regards to genistein, look at this:

http://www.pubmedcentral.nih.gov/articl ... gure&id=F4


Am I reading that right? It appears that downstream of cultivation with androgens, almost nada happens with these cells when genistein is added, but we know genistein doesn't block receptors (but it does downregulate androgen-receptor expression, which is well-known scientifically now as the following link demonstrates: (http://linkinghub.elsevier.com/retrieve ... 3803004688)



It appears some genes dont get expressed despite of androgenic uptake in the presence of genistein: http://www.ars.usda.gov/research/public ... 115=168447

[Expression of androgen- and estrogen-regulated genes was measured in LNCaP cells cultured in the presence or absence of hormonal stimulation and the presence or absence of genistein. Genistein strongly suppressed basal expression of androgen-responsive gene (ARG) mRNAs, including prostate specific antigen (PSA) and Ste20-related proline-alanine rich kinase (SPAK), in LNCaP cells grown in 10% FBS. However, genistein had little or no effect on basal expression of two other ARGs beta2-microglobulin (B2M) or selenoprotein P (SEPP1) mRNA under similar cell growth conditions. Culturing LNCaP cells in the presence of the synthetic androgen R1881 induced increases in PSA, SPAK, B2M and SEPP1 mRNAs. The R1881-induced expression of these genes was uniformly blocked by genistein. For PSA and SPAK, genistein also blocked or down-regulated 17beta-estradiol-induced increases in mRNA expression. These results indicate that genistein selectively alters expression of ARG mRNAs in LNCaP cells through modulation of both androgen- and estrogen-induced signaling pathway. Based on these results, we proposed that the regulation of androgen receptor- as well as estrogen receptor-mediated events is potentially relevant chemopreventive mechanism for genistein administered at physiologic levels. /quote]

OK. Reading the above it seems that some genes, including PSA and SPAK are not expressed by a particular prostate cell line when cultured in the presence of genistein and androgen that are expressed normally in the presence of just androgen. However at least 2 other genes, B2M and SEPP1 were expressed as they would be normally in the presence of androgen. It is hard to know what to make of this in regards to dermal papillae cells. If as you say they genistein is not an antagonist then...I dunno. It downregulates some genes. But not all. Interesting that it also downregulated expression of at least 2 of those genes, PSA and SPAK, from their expression levels in response to estradiol. So its possibly something happening downstream of the androgen receptor but its not affecting all genes that androgens lead to overexpression of. What effect it would have on hair where different genes are expressed in response to androgen, apart from the 5 alpha reductase inhibiting and/or androgen receptor downregulation effects you mention, is anyones guess.

[quote:1x6pszaw]

Harold,
If I remember right, the whole cell assay inhibition of alpha five reductase by genistein was 22% for type one and 89% for type two (Im certain about the later). Genistein has been shown to NOT BLOCK the androgen receptor in experiments (I have links for that), but the downstream gene activity, according the the first graph (the first link in this post) seem to demonstrate that genistein inhibits more downstream androgenic-stimulated gene activity than hydroxyflutamide or RU58841. The USDA article seems to indicate things downstream of androgen uptake that should be happening simply dont in the presence of genistein......................................maybe this is an explanation why sebum levels are so drastically reduced by topical soy in those rats and on people's faces despite the fact that genistein and daidzien are supposedly only "so-so" alpha five reductase type one inhibitiors?



One more thingy...........................and this IS interesting, Apparently neo-natal exposure to genistein lessens the expression of both androgen and estrogen receptors to the baby mice when born:

[quote:1x6pszaw]Neonatal exposure to genistein reduces expression of estrogen receptor alpha and androgen receptor in testes of adult mice.Shibayama T, Fukata H, Sakurai K, Adachi T, Komiyama M, Iguchi T, Mori C.
Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama.

We investigated the long-term estrogenic influence of genistein on the male reproductive system in mice. Newborn ICR male mice were treated with genistein (10, 100, or 1,000 microg/mouse) for neonatal 5 days. As positive control, administration of diethylstilbestrol (0.5-50 microg/mouse) was carried out. In mice exposed to genistein,we examined weight of testes, sperm counts, sperm motility, and mRNA expression levels of estrogen receptor a (ERalpha) and androgen receptor (AR) at 4, 8 or 12 weeks after birth. Moreover, at 12 weeks of age, we evaluated protein level of ERalpha. In our conventional reproductive-toxicological study (weight of testes, sperm counts and sperm motility), neonatal transient exposure to genistein did not show adverse effects on the male reproductive system in 4, 8 or 12 week old mice. However, in mice treated with genistein mRNA expression levels of ERa and AR were reduced at 8 weeks. This reduction was recovered at 12 weeks in mice treated with a lower dose (10 microg) of genistein but not in those with higher doses (100 microg and 1,000 microg). In addition, ERa protein levels tended to decrease in 12 weeks of adulthood. Our results exhibited that the disruption of gene expression continued for long term such as 3 months after administration of genistein, even if no effect was found at conventional reproductive-toxicological level. We have shown that neonatal administration of weak estrogenic compound (genistein) affects male reproductive organs at molecular levels in adulthood.

[/quote:1x6pszaw]



Perhaps this is why Asian men born in Asia who still eat the traditional soy-heavy diet have little body hair, but nice head hair..................and comparitively little acne? Do they have less androgen receptor expression PERIOD due to both eating soya but somewhat less intense androgen receptor expression due to their mothers eating soy?






Parting shot: On male pattern baldness-research, (I dont like that site much either), they DID note that experiments with high fat diets dont indicate the hairloss effect that researchers expected, and that its been suggested that the fact that SOY is eaten a great deal in the east might be the reason that Asians with the traditional diet still have nice hair vs. urban Asians whose hair isn't as good as it was sixty years ago (and now have more acne in adolescence). Internal soy isoflavone only decreases serum DHT by something like 15 percent though........................perhaps topical soy isoflavones might be very very effective in male pattern baldness?

Any thoughts? Am I reading this 'wrong'?[/quote:1x6pszaw]

Soy products and phytoestrogens do seem to interfere with all sorts of male characteristics in rats and so forth. What you say could be quite true. On the flipside of Asian hair and androgens older Japanese males seem to be much less sexually active than their Western counterparts.....there was an abstract on that somewhere.
Win some, lose some....
hh

 

[harold]

Here it is.

Urology. 1999 Aug;54(2):335-44; discussion 344-5.
Decline of sexual function with age in Japanese men compared with American men--results of two community-based studies.
Masumori N, Tsukamoto T, Kumamoto Y, Panser LA, Rhodes T, Girman CJ, Lieber MM, Jacobsen SJ.

Department of Urology, Sapporo Medical University School of Medicine, Japan.

OBJECTIVES: To investigate the self-reported sexual function of Japanese men aged 40 to 79 years in a community-based study and compare the results to a similarly conducted study in Olmsted County, Minnesota. METHODS: Two hundred eighty-nine Japanese and 2115 American men from the community were queried about ability to have erections when stimulated, sexual drive, and satisfaction with sexual activity using a self-administered questionnaire. RESULTS: Both Japanese and American men showed an age-related decline in erectile function, sexual libido, and sexual satisfaction. In particular, 71% of Japanese men aged 70 to 79 years reported having erections only a little of the time or less when sexually stimulated, and 80% perceived sexual drive once per month or less during the past month. Although more Japanese than American men reported erectile dysfunction and decreased libido, there were no striking differences in self-reported sexual satisfaction between the studies. However, cultural and perceptual differences could play a role in these results, despite attempts to ensure linguistic equivalency in the questionnaires. CONCLUSIONS: Although erectile dysfunction and decreased libido were noted by a greater proportion of Japanese than American men, the self-reported degree of satisfaction was comparable between the studies. Perceptions of elderly male sexual function and its impact on health-related quality of life may differ among races, sites, and countries.

 

[michael barry]

Harold, I was thinking abouit genistein in a topical, not internal, capacity....................so hopefully the side effects would be vastly diminished if evident at all.


Fluridil, based on the women's hirsutism study, still seems to be the best topical no-side-effect anti-androgen out there. It pretty much got rid of that one woman's moustache that was pictured, and that is more than any other topical anti-androgen has showed in a study thusfar.

 

[harold]

Just edited the above post to make my reply to your earlier question more visible.
Not sure if systemic soy is even really a concern for adult males. At least in dietary terms. I think the effects in rats are with pretty big doses. I havent looked into it so if anyone has then they would have a better handle on it.
Fluridil....had a bit of a not so impressive encounter with fluridil myself. Basically I was hoping for it to enable me to go off finasteride a couple of years ago but it didnt seem to do the job. I havent seen the hirsutism study. I think they had the right idea but a chemical designed to break down on exposure to water is just too fragile IMO. The body is a pretty aqueous place. I dunno. I had high hopes at the time but it didnt seem to work out.
hh

 

[michael barry]

http://www.med.muni.cz/biomedjournal/pd ... /49_58.pdf

there is the hirsutism study (with the pic). I noticed that it was done in the Czech republic and that is problematic.