[Lotus]

Why improving receptor sensitivity is important for NBE,


Regulation of hormone receptors is very important for a normal functioning cell. There are several ways a cell regulates its hormone receptors. Below is an outline of such regulatory functions:

Regulating the expression of receptors - changing the number of receptors on the plasma membrane.
1. Up regulation - increasing the number of receptors
2. Down regulation - decreasing the number of receptors

Mechanism:
-internalization - endocytosis of receptors
-modify transcription - inhibiting or stimulating transcription factors
-modify receptor half-life - adding groups to the receptors which will degrade them faster


Downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external variable. An increase of a cellular component is called upregulation.

An example of downregulation is the cellular decrease in the number of receptors to a molecule, such as a hormone or neurotransmitter, which reduces the cell's sensitivity to the molecule. This phenomenon is an example of a locally acting negative feedback mechanism.

An example of upregulation is the increased number of cytochrome P450 enzymes in liver cells when xenobiotic molecules such as dioxin are administered (resulting in greater degradation of these molecules).

Most receptor agonists downregulate their respective receptor(s), while most receptor antagonists upregulate their respective receptor(s). The disequilibrium caused by these changes often causes withdrawal when the long-term use of a medication or drug is discontinued. However, the chronic use of certain receptor antagonists may also damage receptors faster than they upregulate.

Upregulation and downregulation can also happen as a response to toxins or hormones. An example of upregulation in pregnancy is hormones that cause cells in the uterus to become more sensitive to oxytocin.

An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. Whereas an agonist causes an action, an antagonist blocks the action of the agonist and an inverse agonist causes an action opposite to that of the agonist.



   

Downregulation and upregulation
http://wikipedia.org/wiki/Downregulation...regulation

Any questions?,

Question- what triggers tissue growth in order for NBE to work?

[Lotus]

Change your receptors, change your set point

Receptor regulation.

Receptors are “message receivers” located throughout our bodies. They are typically transmembrane proteins located on the surfaces of cells, and they bind with hormones and neurotransmitters to “receive” the signal and initiate a sequence of changes in our bodies — often profound system-wide changes in energy utilization, tissue growth, or the perception of pleasure and pain. For some reason, receptors don’t get the public attention that gets showered on the communication chemicals — the hormones and neurotransmitters. And yet, as I shall argue, the receptors may be far more important than the signaling compounds that they interact with, because they do not change by the minute or hour, but are long-lasting parts of the control systems of our bodies. If hormones and neurotransmitters are the “software”, receptors are the “hardware”.

The key process to understand is called receptor regulation, the process which controls the number, location and sensitivity of receptors. There are two forms: upregulation (an increase in the number and/or sensitivity of receptors in each cell) and downregulation (the reverse process). Wikipedia explains downregulation by describing how insulin resistance develops in response to elevated insulin levels:

The process of downregulation occurs when there are elevated levels of the hormone insulin in the blood. When insulin binds to its receptors on the surface of a cell, the hormone receptor complex undergoes endocytosis and is subsequently attacked by intracellular lysosomal enzymes. The internalization of the insulin molecules provides a pathway for degradation of the hormone as well as for regulation of the number of sites that are available for binding on the cell’s surface without doubts. At high plasma concentrations, the number of surface receptors for insulin is gradually reduced by the accelerated rate of receptor internalization and degradation brought about by increased hormonal binding. The rate of synthesis of new receptors within the endoplasmic reticulum and their insertion in the plasma membrane do not keep pace with their rate of destruction. Over time, this self-induced loss of target cell receptors for insulin reduces the target cell’s sensitivity to the elevated hormone concentration. The process of decreasing the number of receptor sites is virtually the same for all hormones; it varies only in the receptor hormone complex. (Italics added by me for emphasis).

So not only are the insulin receptors drawn inside the cell (like a turtle into its shell); they are also actively digested and degraded, making them less available to readily redeploy when glucose and insulin levels drop again. New receptors are always being synthesized, but they are degraded more quickly than they can be replenished if insulin levels remain high. The resulting downregulation of insulin receptors forms the basis for the condition of insulin resistance, in which insulin at normal levels loses its ability to efficiently shuttle glucose from the bloodstream into liver, muscle, brain, adipose or other tissues; the body responds by further increasing insulin, resulting in a vicious cycle of hyperinsulinemia. Reversing this process — growing new insulin receptors — takes time and requires sustained periods with low circulating levels of insulin in order to foster the growth of new receptors.

It is quite revealing to look at how how receptor regulation can undermine “message control” treatments, due to the way the body adapts. Let’s take a look again at how this plays out in the above three examples of obesity, addiction, and depression:
http://gettingstronger.org/2010/10/chang...-setpoint/

Want to optimize your receptors?, read the article....

[Dynseli]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577460/ Genistein possibly increasing sensitivity on ER-alpha. It is a study about cancer cells.

[KinakoNeko]

I love that your threads are so informative and relevant that I can actually apply and use this outside of NBE. Great info, Lotus...thank you!
<3

[Lotus]

Thanks for the linked study and post.

[Lotus]

I love that your threads are so informative and relevant that I can actually apply and use this outside of NBE. Great info, Lotus...thank you!
<3

Thanks Kinako, I think this statement is pretty cool:

If hormones and neurotransmitters are the “software”, receptors are the “hardware”.

[Dynseli]

(Dietary) copper regulates receptors. http://press.endocrine.org/doi/full/10.1...002-221054 "Discussion" section. too high levels cause estrogen excess, and can cause problems during pregnancy.

(Dietary) chromium decreases ER-alpha proteins (in cancer cells but believed to do this in healthy cells too), decreasing sensitivity.(lacking source)

"breast cancer patients have abnormal levels of copper (Cu), Zn, Se, and Cd" (Copper, Zinc, Selenium, Cadmium) "here is also some evidence for an inverse association between Zn and breast cancer, while there is no association between exposure to Se and the risk of breast, colorectal, and stomach cancer and between Zn and the risk to develop prostate cancer [12]. Nevertheless, positive associations of breast cancer with Zn, iron, and calcium, but little association with Se, have been reported in [17]." http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143443/

Small amounts of chromium and copper found in food are essential trace nutrients. Excess of dietary estrogenic metals is carcinogenic. Other estrogenic metals are carinogenic. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671233/

Calcium is an exception, as it is linked to reduced risk of breast cancer, http://www.eurekalert.org/pub_releases/2...041210.php.

[wizzness]

Hey lotus! I just read this article posted on the 'Sythetic oestrogen vs PM' thread as part of a discussion about the role of progesterone in growing breats: http://www.gender.org.uk/gendys/2009/47curtis.htm

I've experienced an increase in size with my progesterone-heavy bcp & goat's rue, but now I'm wondering if it's just water weight/ general weight gain and tipping the balance towards oestrogen might be a better idea? I've heard some proclaim that you can grow with just progesterone & prolactin promotion, but this seems to suggest that growth is down to oestrogen and that progesterone reduced oestrogen receptors....reckon I should stop bcp to re-sensitise myself to oestrogen or take more oestrogen with the bcp?

[Lotus]

Hey lotus! I just read this article posted on the 'Sythetic oestrogen vs PM' thread as part of a discussion about the role of progesterone in growing breats: http://www.gender.org.uk/gendys/2009/47curtis.htm

I've experienced an increase in size with my progesterone-heavy bcp & goat's rue, but now I'm wondering if it's just water weight/ general weight gain and tipping the balance towards oestrogen might be a better idea? I've heard some proclaim that you can grow with just progesterone & prolactin promotion, but this seems to suggest that growth is down to oestrogen and that progesterone reduced oestrogen receptors....reckon I should stop bcp to re-sensitise myself to oestrogen or take more oestrogen with the bcp?

Hi wizz,

I've seen this article before, I've also seen this one by Dr. Curtis.
The dangers of the internet and unsupervised prescribing
http://www.gender.org.uk/gendys/2007/39curtis.htm

• The question I came away with was no sourced studies are linked, that's not to say it's not legitimate, accompanying studies back up the research.
  

• I started using PC last year and although I have to say it gives a nasty aggressive nature, it did provide side branching and elongation.
  

• What's the BCP dose and how long have you been on it?
  

I've looked into this before, I have more info but thought what I posted was most relevant. I'd have to look and see if any of the info has change but it's not that old.

• Prolactin and progesterone may enhance ductal outgrowth by inducing ERα expression.
  

• Activation of ER-α causes elongation or horizontal growth of mammary duct cells. Progesterone receptor activation causes side-branching of mammary gland cells. Density, areolar gland development, and gland lactation development are caused by prolactin receptor activation.
  

Check pages 5 thru 9
Hormone Action in the Mammary Gland
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2982168/

I found these statements and wanted more info, granted, some of the info comes from sites that are selling products. However, not much easily identifiable info is given while researching for PC and Bio-males without a product being offered or from a scientific abstract which are difficult to decipher.

(5-alpha reductase inhibitors such as finasteride are usually given to prevent the conversion of testosterone to DHT, but research has found that progesterone is a natural inhibitor of 5-alpha reductase.)

Read more: http://www.progesteronetherapy.com/proge...z2uY1QWH3r
Under Creative Commons License: Attribution

Progesterone 5alpha-reductase- http://wikipedia.org/wiki/Progesterone_5alpha-reductase

• Progesterone is used in hormone therapy for transsexual women, and some intersex women - especially when synthetic progestins have been ineffective or caused side-effects - since normal breast tissue cannot develop except in the presence of both progestogen and estrogen. Mammary glandular tissue is otherwise fibrotic, the breast shape conical and the areola immature. Progesterone can correct those even after years of inadequate hormonal treatment. Research usually cited against such value was conducted using Provera, a synthetic progestin. Progesterone also has a role in skin elasticity and bone strength, in respiration, in nerve tissue and in female sexuality, and the presence of progesterone receptors in certain muscle and fat tissue may hint at a role in sexually-dimorphic proportions of those.

Progesterone may effect male behavior: 'Progesterone receptors mediate male aggression toward infants' PNAS 2003 100: 2951-2956; 10.1073/pnas.0130100100



More interesting facts:

• Men need it to make testosterone and for the adrenal glands to make cortisone
  
• Progesterone in males is created during testicular production of testosterone
  
• Men with BPH (swelling of the prostate) and other male related problems report that they experience some relief with progesterone cream
  
• Progesterone has NO feminizing characteristics
  
• Men report that it helps them with complexion and increases energy
  
• It is believed to help balance the estrogens that build in a man's body
  because progesterone levels drop, estradiol levels rise, and testosterone changes in form in older men
  
• Adding progesterone back into the body helps restore normal inhibition of 5-alpha-reductase, thus preventing testosterone from changing into dihydrotestosterone (DHT), which stimulates proliferation of prostate cells
  
• If men have low progesterone levels their estradiol levels can increase. This increase can lead to cancer of the prostate, just as it leads to breast and uterine cancer in
  women

http://www.vienuetestosterone.com/refere...terone.asp



Progesterone cream can help to reduce the prostate size. Progesterone's inhibitory effect on 5 alpha reductase is far more effective than Proscar which is standard agents used in traditional medicine to cure BPH. All men over age 40 should consider natural progesterone replacement therapy, or even earlier if there is a history of prostate caner or BPH. The amount needed is 8 - 12 mg a day (1/8 tsp -1/4 tsp twice daily). Men should apply directly to their scrotum (testical sac) twice daily. This allows it to get into the prostate receptors. http://www.bluemountainrx.com/progesterone_men.htm


Characterization and localization of progesterone 5 alpha-reductase from cell cultures of foxglove (Digitalis lanata EHRH)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1131093/


Role of 5 alpha-reductase inhibitors in the management of prostate cancer
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699636/

A high affinity inhibitor of pituitary progesterone 5 alpha-reductase.
http://www.ncbi.nlm.nih.gov/pubmed/6581041

[Lotus]

Medroxyprogesterone is a synthetic progestin with various side effects, see the article below to highlight the difference of synthetic progestin vs. Progesterone.



The Safe and Effective Alternative to Provera®
Natural Progesterone
http://www.life-enhancement.com/magazine...lentine-do