Hormone menubar
Estrogens - The Female Hormones
ESTRIOL (E3) - The WEAK, Protective Estrogen
Comparing the estrogens
ESTRONE(E1),
ESTRADIOL (E2) and
ESTRIOL(E3) fluctuate
with life stage. Suggesting specific roles for them in biological
and disease processes.
- Fluctuations of ovarian
hormones in perimenopause consist of
intermittent high and low ESTRADIOL (E2)
levels, followed eventually by
chronically lower levels, and the predominance of
ESTRONE (E1) .
T hese changes can be correlated with behavioral & other disturbances and
pubertal and menstrual cycle-based fluctuations.
Changing levels of these estrogens could be instrumental in
tissue development, function, and some lifestage-specific diseases in women
ESTRADIOL,
ESTRONE
and ESTRIOL
are produced
by aromatase
enzymes in non-reproductive tissues (E.g. brain, fat cells).
With possible effects on
non-reproductive functions.
• E.g.
ESTRIOL
(E3) has protective effects against the development of arthritis in certain
experimental models -ESTRADIOL
(E2)
• These estrogens
could make a difference. In the brain, bone,
cardiovascular system and many other tissues during
different life stages.
-
ESTRADIOL (E2, 17ß-ESTRADIOL)
• The
predominant form in NON-pregnant females from menarche to menopause
• The most powerful and most carcinogenic.
- ESTRONE (E1)
•
•
70% less biologically active than
ESTRADIOL
•
ESTRONE
(E1) is a significantestrogenic hormone contributor in both
reproductive
(0.5-1
nM) and postmenopausal
(150-200
pM) women and in
men ;
- ESTRIOL (E3)
• Comprises nearly 80% of the total free estrogen
• Produced during PREGNANCY in much greater
quantities than ESTRONE and ESTRADIOL -
10-100 nM pregnant women and <7 nM non-pregnant women
Decreased ESTRIOL
(E3)
levels in pregnancy have been associated with complications of eclampsia and the
incidence of Down's syndrome in offspring.
ESTRIOL,
ESTRONE, ESTRADIOL - Weak or Strong estrogens ?
The physiological effects of
estrogens
are mediated by the intracellular estrogen receptors (ERs). In response to estrogens ,
xenoestrogens and signals emanating from
growth factor signalling pathways, they regulate:
(i) Genomic pathway initiation
of gene expression (transcription) of target genes
(for protein synthesis)
(ii) Non-genomic pathway
functions
Specific effects of
estrogens depend on:
• ER subtype
in tissue ( ER-αand ER-β).
E.g. ER-αpredominates inthe uterus and
mammary gland, whereas ER-β
has significant roles in the central nervous, cardiovascular, and immune
systems; urogenital tract, bone, kidney, and lungs;
• Number of receptors
- varies by location and whether pre- or post-menopause
ESTRONE(E1) and
ESTRIOL(E3)
are
STRONG estrogens
in the NON-genomic signaling pathways and functional pathways of
pituitary
Watson CS, Jeng YJ, Kochukov MY. Nongenomic actions of ESTRADIOL compared with
estrone and estriol in pituitary tumor cell signaling and proliferation. FASEB
J. 2008 Sep;22(9):3328-36. doi: 10.1096/fj.08-107672. Epub 2008 Jun 9.
PubMed
ESTRONE(E1)
and ESTRIOL(E3) are
WEAK
estrogens
in the GENOMIC pathway (affecting nuclear transcription
activity)
ESTRADIOL (E2)
is STRONG in the GENOMIC and NON-genomic pathways
-
although
ESTRADIOL
(E2) (in the high pM to
nM range) is the physiological
estrogen
most often associated with GENOMIC pathways in
female
reproduction and the development of cancers in reproductive tissues.
-
ESTRADIOL(E2)
is stronger than ESTRONE(E1)
and ESTRIOL(E3) in cell proliferation - E2
effects were evident at fM (Femtomolar - 1.0 fM is 1 million times smaller than
a nM ) levels, whereas E1 and
E3 were effective at 1 pM and 0.1 nM and
above, respectively.
Watson Cheryl S. et al,Nongenomic actions of ESTRADIOL compared with ESTRONE and ESTRIOL in
pituitary tumor cell signaling and proliferation, The FASEB J. 2008 September,
22(9): 3328-3336
