New study below. (This is mainly for Nalakrats.)
Aromatase is an enzyme that converts testosterone to estrogen.
Twenty years ago, from a Japanese team:
"aromatase expression in human prostate was not associated with malignancy {since it is also present in BPH}. However, overexpression of aromatase, possibly attributable to abnormal gene regulation, may result in estrogen production in situ and play a role in the induction or development of human prostatic disorders." [2]
From a 2004 Australian paper [3]:
"Local aromatase expression in human prostate is altered in malignancy."
Note that in the healthy prostate, the estrogen receptor found in epithelial cells (where cancer occurs) is the beta [ERbeta]. The natural ligand for ERbeta is actually a metabolite of the androgen DHT. The cells have no need to convert testosterone to estradiol [E2].
ERalpha is found in the stroma, so the presence of aromatase is not surprising, since the natural ligand is E2.
From the Australians (2006) [4]:
"Paradoxically, the incidence of prostate disease increases with age when serum androgen levels are in decline and emerging evidence suggests that estrogens may also be important in the normal prostate, as well as in the etiology of prostate disease. Both estrogen receptor subtypes are present in the prostate, demonstrating that the gland responds directly to estrogens. Recent data suggests that estrogens play a role in prostate disease and has demonstrated that high doses of estrogens induce premalignant dysplasia and in combination with high doses of androgens, malignancy. The production of estrogens from androgens is mediated by the aromatase enzyme, the aberrant expression of which plays a critical role in the disease process in other tissues, most notably the breast. The prostate expresses aromatase within the stroma of benign tissue, while in malignancy there is an induction of epithelial expression with altered promoter utilisation."
An Italian (2007) [5]:
"although multiple consistent evidence suggests that estrogens are critical players in human prostate cancer, their role has been only recently reconsidered, being eclipsed for years by an androgen-dominated interest."
Ten years later & I'm still waiting!
From the new paper:
"Interestingly, animals lacking aromatase do not develop {prostate} cancer or prostatitis, whereas those with overexpression of aromatase and consequently high estrogen levels, develop prostatitis and squamous metaplasia via estrogen receptor 1 (ERα)."
"in senile rats, there was an increase in the frequency of basal cells intensely stained for aromatase, which appeared concentrated in areas of intraepithelial proliferation and prostatitis. These punctual areas also presented increased ERα positivity."
None of us are senite Wistar rats, but it's been known for at least a dozen years that PCa cells lose ERbeta & gain ERalpha - & start producing aromatase.
The new study is from Brazil. American PCa researchers seem uninterested in estrogen.
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/291...
[2] ncbi.nlm.nih.gov/pubmed/914...
[3] ncbi.nlm.nih.gov/pubmed/151...
Inhibition of estrogen signaling through depletion of estrogen receptor alpha by ursolic acid and betulinic acid from Prunella vulgaris var.
