Once inside the cell, an estrogenic hormone binds to estrogen receptors (ERs) to activate them
- Binding modulates the expression of many genes. Leading to formation of messenger RNA (mRNA);
- mRNA interacts with ribosomes to produce proteins that express a specific effect of estrogen upon the target cell
Two types of estrogen receptors
• ER-αreceptors. Found in the endometrium uterus, breast cancer cells, ovarian stroma cells, hypothalamus, testes, dermal papilla cells (fingerprints /nourish hair follicles and bring food and oxygen to the lower layers of epidermal cells), sebaceous glands and adrenal glands.
• ER- βreceptors. Discovered 1996, present in the same areas as ER-α to a degree, but also found in more diverse parts of the body, including the skin, brain, kidney, bone heart, lungs, intestinal mucosa, prostate and endothelial cells (line the interior surface of blood vessels).
- Skin / Hair follicle receptors. ER-β (and not ER-α) is the main mediator of estrogen action in human skin and the hair follicle. ER-β is highly expressed in epidermis, dermal fibroblasts, and outer root sheath of the hair
http://www.nature.com/jidsp/journal/v8/n1/full/5640100a.html
HUMAN |
ER-α |
ER- β |
AR |
PR |
|
Epidermis |
ER- β |
|||
|
Dermal fibroblasts |
ER- β |
|||
|
Outer root sheath of hair follicle |
ER- β |
|||
|
Dermal papilla cells |
ER-α |
AR |
||
|
Sebaceous glands |
ER-α |
ER- β |
AR |
|
|
Eccrine sweat glands |
ER- β |
AR |
PR |
|
|
Adipose Tissue (subcutaneous) |
ER- β |
Binding affinity of different estrogens
• ESTRADIOL binds equally well to both ER-α and ER-β
• ESTRONE binds preferentially to ER-α
• ESTRIOL (postmenopausal estrogen) and genistein (Isoflavones) bind preferentially to ER-β
ER amounts ▼ decrease significantly after menopause
ESTRADIOL increases number of ER-α and AR receptors
- ESTRADIOL stimulates production of both ER-αreceptors and androgen receptors (Ars) - promoting a greater hormonal effect for estrogen and androgens;
- Also, even a low dose of the synthetic estrogen bisphenol A (prolific in our world and bodies today - see xenoestrogens) has the same effect as natural ESTRADIOL.
Richter CA, JA Taylor, RL Ruhlen, WV Welshons and FS vom Saal. 2007. ESTRADIOL and bisphenol a stimulate androgen receptor and estrogen receptor gene expression in fetal mouse prostate mesenchyme cells,. Environmental Health Perspectives, in press. Link
- Stimulation is blocked by estrogen receptor antagonists - E.g. PROGESTERONE , tamoxifen,
ESTRADIOL is a relatively potent androgen receptor (AR) binder;
Nakla AM, Romas NA, Rosner W. ESTRADIOL Activates the Prostate Androgen Receptor and Prostate-specific Antigen Secretion through the Intermediacy of Sex Hormone-binding Globulin March 14, 1997 The Journal of Biological Chemistry, 272, 6838-6841. Jbc Abstract
RichterCA, JA Taylor, RL Ruhlen, WV Welshons and FS vom Saal. 2007. ESTRADIOL and bisphenol a stimulate androgen receptor and estrogen receptor gene expression in fetal mouse prostate mesenchyme cells,. Environmental Health Perspectives, in press. Link
Leslie Baumann. Cosmetic Dermatology: Principles and Practice, Second EditionMcGraw Hill Professional,Apr 8, 2009
