Quote from: Randi on July 03, 2014, 01:53:31 PM
Estrogen receptors are not CREATED by estrogen, they are ACTIVATED by estrogen. Generally the number of estrogen receptors doesn't change and is roughly equivalent in men and women, with the exception of body parts, such as a uterus that are not present.
My understanding was that the number of receptors for steroid hormones is never constant and can be upregulated (increased) or downregulated (decreased) by various hormones. For instance, estrogen according to what some studies suggest, downregulates androgen receptors, while estrogen upregulates progesterone receptors and progesterone downregulates estrogen receptors.
So, if this is right, then one should expect the number of receptors to vary according to one's hormonal environment and change from the time we are hormonally "male" to "female".
http://www.ncbi.nlm.nih.gov/books/NBK20/"Receptor regulation is an important part of endocrine function and this occurs through up or down-regulation of the number of receptors and by desensitization of the receptors."
http://www.biomedcentral.com/1471-2121/11/98"ERα is a short-lived protein (half-life of >3 h for unbound ERα and ~ 1-3 h for ligand-bound ERα) [10,31]. ERα degradation occurs in presence of natural ligands (E2) or pure antiestrogens"
The Human Estrogen Receptor-α Is a Ubiquitinated Protein Whose Stability Is Affected Differentially by Agonists, Antagonists, and Selective Estrogen Receptor Modulators*September 21, 2001 The Journal of Biological Chemistry, 276"the half-life of ERα is about 4–5 h, whereas estradiol binding accelerates receptor degradation, reducing its half-life to ∼3–4 h (13-17)."
http://www.ncbi.nlm.nih.gov/pubmed/18096994"Upon initial hormone treatment, ERalpha half-life is shortened from 3 to 1 h. However, ERalpha half-life increases over time, achieving a half-life of approximately 6 h in 72 h of estrogen treatment."
Quote from: Randi on July 03, 2014, 02:22:45 PM
The liver is constantly filtering the blood and eventually ALL estrogen will be broken down and eliminated from the body.
My understanding is that the estrogen that binds to estrogen receptors in tissues outside of the liver is done for and "dies", in a sense, having done its job so will not end up in the liver. This is the advantage of taking estrogen non-orally, that much less estrogen ends up circulating through the liver as all of it goes directly into the blood (versus going through the liver, "first pass" effect) and much of it enters all tissues of the body, thus avoiding the liver, and minimizing the amount that ends up in the liver. If that wasn't the case and ALL estrogen were to end up in the liver even non-orally, then what would be the advantage of taking it non-orally, healthwise? Why does non-oral appear to be less harmful than oral?
http://www.ncbi.nlm.nih.gov/pubmed/3306522"The systemic administration of estradiol avoids this initial hepatic metabolism. Furthermore, only 25 per cent of nonorally administered estrogen will go to the liver at each pass, and nonhepatic tissues would be exposed to a greater extent than after oral administration. Thus, peripheral administration of estradiol reduces the exaggerated hepatic responses in comparison to nonhepatic actions."
http://www.ncbi.nlm.nih.gov/pubmed/18775609"This paper reviews the role of the non-oral route of administration of sex steroids in the clinical management of postmenopausal women. Non-orally administered estrogens, minimizing the hepatic induction of clotting factors and others proteins associated with the first-pass effect, are associated with potential advantages on the cardiovascular system. In particular, the risk of developing deep vein thrombosis or pulmonary thromboembolism is negligible in comparison to that associated with oral estrogens."
