To Estriol Or Not To Estriol
That has become THE question!
Hormones are largely, not totally, about a hormone (called a ligand) signaling into a “receptor” by nestling on into an evolutionarily conserved “parking spot” called a “binding domain”.
There are many estrogen receptors. As estrogen is the oldest hormone on the planet.
The first hormone, says estrogen historian and scientist, Dr. Michael Baker, was the estrogen receptor.
Estradiol is such a complex hormone, only the receptor, as life unfolded, first existed.
What signaled it? Bits of male hormone and bits of androstenedione. A pro-hormone.
Estradiol is so complex, Dr. Baker states it took a while for estradiol, the hormone, to show up.
Now we know that estrogen might have many receptors, some we don’t know about yet much. Perhaps even up to 12 or 14.
But the first three receptors estrogen receptors are best known.
They are:
ER Alpha: what signals this creates diverse physiologic actions. Not simple. But in simple terms we can rightfully say that whatever signals this first receptor, thus dubbed Alpha, stimulates heart beat, blood flow, brain plasticity, renal plasticity.
Signals to ER alpha are often simplistically described as promoting “growth”.
ER Beta: what signals ER beta tamps down inflammation. Helps the body fight cancer. Keeps mood levels more even. (ER beta receptors “live” right on top of oxytocin receptors all over the brain, especially in mood and memory anatomical areas).
ER Alpha and ER Beta live inside the cytoplasm in the “belly” of cells.
The estrogen molecules must cross the cell membrane, travel into the cellular “guts” and seek out the binding pocket.
“If” it is available, as receptors must NOT have other hormones like cortisol or pollutants like endocrine disruptors such as plastics, already “squatting” inside the pocket. Then estrogen can’t park. Can’t deliver its messages. To genes.
Hormone health = all about “receptor functionality”. (That’s why my new products help clear pollutants and keep hormones balanced to get better global hormonal signaling).
Since estrogen has to travel cross hill and dale to get inside the belly of cells, and nutrients must be present (zinc, iodine, Vitamin D, Vitamin B6, magnesium and sometimes even other moieties), this is the slower form of hormone signaling.
Signals to ER Alph and ER Beta are called “genomic” signaling.
As they signal “genes”. To tell cells what to do.
They do this through secretarial skills of “transcribing” the message to genes. To keep you well.
We call genomic signaling, thus, transcriptional signaling.
This signaling is a bit more lumbering and slower than non-genomic signaling.
Estrogen’s major “non-genomic” signal comes from GPER that lives inside cell membranes.
Not in the belly of the cell, but on the cell’s “skin”.
GPER: Stands for G protein-coupled estrogen receptor.
GPER: This is not a ligand-receptor binding estrogenic receptor, but when triggered releases a cascade of enzymes. This is a much more rapid form of hormonal message. (Unless you eat a highly processed diet that has “bad” and “trans” fats, then the cell’s skin gets hardened and these signals can falter).
For example, GPER membraneous receptors line the gut, in the gut’s nervous system (enteric nervous system).
GPER signals are instantaneous. Thus, rapid “gut feelings” to what is “right” or “not right” in our world. Comes a lot from GPER signals in the gut.
That’s why women often exhibit good skills at intuition.
They have more estrogen. That signals GPER more than males.
Intuition or gut feelings come from GPER signals in the enteric gut nervous system.
GPER is non-genomic signaling. It is fast.
“All” hormones, including progesterone and testosterone, have “both” versions of genomic and non-genomic signaling.
We are just learning all this as I write.
Hormones are an unfolding science.
There are three major forms of estrogen that signals these receptors.
Although keep in mind that the body has many estrogenic acting metabolites, perhaps up to 60 molecules, that can deliver signals to estrogen receptors.
So, nothing about hormones is simple.