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Aromatase enzyme converts androgens to estrogens. Find out what affects its activity
Aromatase
enzyme converts androgens to estrogens
Androgens ➔ Estrogens
aromatase enzyme
Aromatase function in more
detailAromatase is responsible for the
production of 18-carbon estrogens from 19-carbon
androgen steroids:TESTOSTERONE and
ANDROSTENEDIONE
- the gene CYP19 encodes the
aromatase enzyme (a member of the Cytochrome
P450 enzyme superfamily).
ANDROSTENEDIONE ➔
ESTRONE (in women )(In the female,
FSH increases aromatase
activity, enhancing this conversion)
TESTOSTERONE ➔
ESTRADIOL. Aromatase productionDifferent body tissues produce
estrogen
via
aromatase
response to different activating promoters tissue-specific regulation
of CYP19 (aromatase
gene) expression is achieved through the use of distinct promoters controlled
by hormones and other factors, including:
•
Glucocorticoids (E.g.
CORTISOL ,
• Class 1 cytokines:
E.g. IFN-γ, IL-2, IL-6, IL-11, and TNF-α(present in infection);
• Retinoids.
E.g. vitamin A
• FSH
Aromatase Gene (CYP19) Expression Regulators
Location
Promoter
Promoter regulated by:
Ovaries
Cyclic AMP via the proximal promoter II
FSH
Placenta
distal promoter I.1
Retinoids
Adipose tissue, skin fibroblasts, bone
distal promoter I.4
Glucocorticoids and class 1 cytokines
E.g. tumor-derived PGE2 is the major factor stimulating local aromatase expression in the breast fat of cancer patients.
Aromatase
can be found in several tissues- Tissues
having beneficial estrogen presence -
includes gonads, brain, adipose tissue placenta, blood vessels, skin, bone, and endometrium.
- Health
conditions where inappropriately high levels of
aromatase
are present in tissues - endometriosis, uterine fibroids,
breast cancer aromatase
activity found in breast fat)and endometrial cancer
What affects aromatase activity?
Aromatase
inhibitor
examples:
-
Nettle root
-
PROGESTERONE
-
Drugs: MEHP (monoethylhexylphthalate); fenarimol;
substituted analogs of ANDROSTENEDIONE, e.g.,
C-10 substituted (19R-10 β-oxiranyl-), or C-4 substituted (OH-, formestone),
or C-7 substituted (7 α-SC6H4-p-NH2-), or 2 β, 19 bridged (2 β, 19-methylene-),
fadrazole, letrozole, and arimidex,
Aromatase ACTIVITY
is ▲Enhanced by:
• Age;
• Obesity;
• INSULIN;
• Gonadotropin hormones (E.g. FSH, LH, hCG);
• Alcohol.
• Location in certain estrogen-dependent
local tissue E.g. next to breast tissue
• Endometrial cancer, endometriosis,
and uterine fibroids.
Aromatase ACTIVITY
is ▼Reduced by:
• PROLACTIN
(stimulates milk production for breast-feeding);
• Smoking;
• Anti-mullerian
hormone (AMH). Produced by reproductive tissues.
Inhibits the development of the Mullerian ducts in the male
embryo, which develop into reproductive organs in females.
• Drugs
(post-menopausal only) Letrozole (Femara® ),
anastrozole (Arimidex® ), and exemestane (Aromasin® ).
Aromatase
conversion pathway directly affected by:
- Flavonoids
and lignans (both
polyphenols) .
Enterolactones are lignan precursors found in E.g.flaxseed;
- Drugs.
Aminoglutethimide, MEHP, Fenarimol, Fadrazole, Letrozole,
Anastrozole, Arimidex, Prochloraz, Enconazole/miconazole/ketoconazole, Imizolil,
4-hydroxyANDROSTENEDIONE, 10-propargylestr-4-ene-3,17-dione
