Aromatase: New study below. (This is... - Advanced Prostate...

Advanced Prostate Cancer

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Aromatase

pjoshea13 profile image
pjoshea13

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...

[4] ncbi.nlm.nih.gov/pubmed/164...

[5] ncbi.nlm.nih.gov/pubmed/177...

7 Replies

Hi Patrick,

Aromatase. It sounds like something benign or beneficial, like aromatherapy. But noooo,

Neal

Aromatase is an odd word. Wonder how it was derived. Does the 'tase give off a distinctive aroma? OK, I know that was a dumb question.

pjoshea13 profile image
pjoshea13 in reply to WSOPeddie

Half correct. "ase" is the suffix for an enzyme. Seemingly, most enzymes lack an aroma. Too bad the namer wasn't more descriptive. I mean, is it pleasantly citrusy or more like unwashed feet? Anything would help.

The more descriptive name is "estrogen synthase", although some might prefer "CYP19A1".

Aromatase actually does two things: it transforms androstenedione to estrone and testosterone to estradiol.

-Patrick

WSOPeddie profile image
WSOPeddie in reply to pjoshea13

Thanks Patrick. We can learn a lot from you.

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Hidden

First line, I am LMAO. Now I'll go and read the rest.

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Hidden

Some compounds were called aromatic because of the smell.

en.wikipedia.org/wiki/Aroma...

The commonality turned out to be a benzene ring which is a 6 carbon ring with alternating double bonds.

Estradiol has a benzene ring whereas testosterone does not.

en.wikipedia.org/wiki/Estra...

en.wikipedia.org/wiki/Testo...

Inhibiting an aromatase from its usual job of forming a benzene ring makes the chemical an aromatase inhibitor.

WSOPeddie profile image
WSOPeddie in reply to Hidden

Cool.

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