Susan's Place Transgender Resources

I've been trying to find information about estrogen receptors in the male body.  Specifically do male have as many receptors as female but inactive or must new receptors be created by estrogen in MTF.  I do google searches but just get a lot generalized crap that doesn't really tell me anything.  Anyone know where I can find answers? 

From Wiki  ER = Estrogen Receptors

QuoteBoth ERs are widely expressed in different tissue types, however there are some notable differences in their expression patterns:[7]

The ERα is found in endometrium, breast cancer cells, ovarian stromal cells, and the hypothalamus.[8] In males, ERα protein is found in the epithelium of the efferent ducts.[9]
The expression of the ERβ protein has been documented in ovarian granulosa cells, kidney, brain, bone, heart,[10] lungs, intestinal mucosa, prostate, and endothelial cells.
The ERs are regarded to be cytoplasmic receptors in their unliganded state, but visualization research has shown that a fraction of the ERs resides in the nucleus.[11] The "ERα" primary transcript gives rise to several alternatively spliced variants of unknown function.

QuoteIn males, ERα protein is found in the epithelium of the efferent ducts.[9]

This part links to here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC179885/

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.

An estrogen molecule fits into the receptor like a key in a lock and allows the cell to make a particular protein.  It's sort of like turning on a switch.

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.

An estrogen molecule fits into the receptor like a key in a lock and allows the cell to make a particular protein.  It's sort of like turning on a switch.

Finally got an answer I can understand.  Google can be like looking for a needle in a haystack.  Can you tell me how much transdermal estrogen is absorbed by the body and thus does not recirculated through the liver? 

There are really two questions there.

With transdermal, only a portion of the available estrogen is actually absorbed though the skin and enters the bloodstream.  This can vary from person to person.

The liver is constantly filtering the blood and eventually ALL estrogen will be broken down and eliminated from the body.

When an oral medication leaves the stomach, it is subjected to that "first pass" in the liver.  Non-Orals, such as Oestrogel, Injections and patches are not subject to that first pass.  The blood is constantly filtered by the liver (and kidneys) if this didn't happen one dose of estrogen would last forever. So there is always a second pass, third pass etc.

Quote from: Amy1988 on July 03, 2014, 02:10:42 PM
Finally got an answer I can understand.  Google can be like looking for a needle in a haystack.  Can you tell me how much transdermal estrogen is absorbed by the body and thus does not recirculated through the liver?

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."

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.

An estrogen molecule fits into the receptor like a key in a lock and allows the cell to make a particular protein.  It's sort of like turning on a switch.

The number of estrogen and androgen receptors, like all others in the body are actually in a constant state of fluctuation.  Many foods, beverages, drugs, and behaviors can upregulate and downregulate these receptors

Quote from: Oriah on July 04, 2014, 02:21:02 AM
The number of estrogen and androgen receptors, like all others in the body are actually in a constant state of fluctuation.  Many foods, beverages, drugs, and behaviors can upregulate and downregulate these receptors

Correct me if I'm wrong, some foods and beverages have something called phenoestrogens which mimic estrogen and therefore can increase receptiveness of estrogen itself?  I remember reading about this foods like flax seed and certain beans and legumes have these estrogen mimicking properties.  I don't knowmthe validity of it though.

We agree on this.  Once the ligand is bound to a receptor, it's done it's job.  Excluding the first pass, the liver only deals with estrogen circulating in the blood.

One question:  Does the liver only break down "free" estrogen, or does it also break down estrogen bound to SHBG?

Quote from: KayXo on July 03, 2014, 06:00:28 PM
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.

Quote from: AnnaCannibal on July 04, 2014, 11:43:03 AM
Correct me if I'm wrong, some foods and beverages have something called phenoestrogens which mimic estrogen and therefore can increase receptiveness of estrogen itself?  I remember reading about this foods like flax seed and certain beans and legumes have these estrogen mimicking properties.  I don't knowmthe validity of it though.

I think however that these estrogens are VERY weak, too weak to have any significant effect. But, in all honesty, it's just a thought. I don't know much about this.

Quote from: Randi on July 04, 2014, 11:43:51 AM
One question:  Does the liver only break down "free" estrogen, or does it also break down estrogen bound to SHBG?

Logically, I would think only free estrogen.

Quote from: Amy1988 on July 03, 2014, 06:24:38 AM
I've been trying to find information about estrogen receptors in the male body.  Specifically do male have as many receptors as female but inactive or must new receptors be created by estrogen in MTF.  I do google searches but just get a lot generalized crap that doesn't really tell me anything.  Anyone know where I can find answers? 

Short version: there is no difference in the quantity of receptors in a given tissue. The availability varies greatly. This is why micromanaging hormone therapy is a bad idea because it spreads the belief that one can "control" autonomic systems that ae feedback based (cellular biology). Taking a different administered route of estradiol than oral helps a lot but the body in any case does what it was intended to do: remove excess amounts of anything (hormone, protein, sodium, water, etc) while uptaking/manufacturing replacement materials for what was lost (by use or filtered out).

ER, AR and PR - all receptors - going permanently through an up- and downregulation. Its controlled by other hormones. Low E2-levels will create new ER, raising P4-levels will create ER too, but P4 downregulates on the other hand ERs for itself. The whole process is really complex.

Quote from: KayXo on July 03, 2014, 06:00:28 PM
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."

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."

Thank you for posting this.  Very interesting information.

Please notice: E2-halflife time is in XY-bodies with 1h shorter than in bodies with xx with 1,6h. It has to do with the differences in its metabolism.

Quote from: galaxy on July 06, 2014, 09:22:18 AM
Please notice: E2-halflife time is in XY-bodies with 1h shorter than in bodies with xx with 1,6h. It has to do with the differences in its metabolism.

Is E2 the 17 Beta estradiol type?  Also does transdermal E2 have a 1-6 hour half-life or just the pill form or both?  I'm really confused about half-life of estrogen because I've seen so many different half-life ratings. 

Quote from: Amy1988 on July 06, 2014, 05:53:07 PM
Is E2 the 17 Beta estradiol type?

Yes, I believe it is.

Quote from: Amy1988Also does transdermal E2 have a 1-6 hour half-life or just the pill form or both?  I'm really confused about half-life of estrogen because I've seen so many different half-life ratings.

From what I gather, it appears that half-life of oral E2 is about 13-17 hours, give or take while for patches, the same amount of estradiol is delivered over 24 hours for the first 3-4 days or 7 days depending on the make of the patch.