And further the REAL QUESTION AS TO THE WHY... You know my thoughts on blood composition as "Serum labs" vs. what MAY really be occurring in metabolic action/transfer.. Estrogen in circulation does not define receptor activity, nor necessarily REFLECT DIRECTLY or with ANY Lines to draw at this time considering all VARIABLES like these discussed here and more. Concerns obviously being..:
1) what a lack of E at the RECEPTORS requiring E is causing TT to do in real action.
2) what the lack of E MAY e causing TT to do at androgen receptors. CLEARLY, A body starved of E is going to attempt to take more TT to the E receptors
and AWAY from androgen receptors.
3) Whether or not CELLS which require BOTH Androgens AND estrogens (
Basically ALL cells I Suspect) can even behave properly AT ALL under conditions of a BLOCKADE or SHORTAGE of EITHER..???!!!?!!
OFF THAN LINE, but on topic...
And I think someone INFERRED "gluten" in this thread somewhere as opposed to "glutamate". I'm not searching the post out, and perhaps just having an "off-Celiac-hating day" LOL.
http://en.wikipedia.org/wiki/Glutamate_receptor
"Ionotropic[edit]
Main article: Ionotropic glutamate receptor
Ionotropic glutamate receptors, by definition, are ligand-gated nonselective cation channels that allow the flow of K+, Na+ and sometimes Ca2+ in response to glutamate binding. (In C. elegans and Drosophila, invertebrate-specific subunits enable the flow of negative chloride ions rather than cations.) Upon binding, the agonist will stimulate direct action of the central pore of the receptor, an ion channel, allowing ion flow and causing excitatory postsynaptic current (EPSC). This current is depolarizing and, if enough glutamate receptors are activated, may trigger an action potential in the postsynaptic neuron. All produce excitatory postsynaptic current, but the speed and duration of the current is different for each type. NMDA receptors have an internal binding site for an Mg2+ ion, creating a voltage-dependent block, which is removed by outward flow of positive current.[17]Since the block must be removed by outward current flow, NMDA receptors rely on the EPSC produced by AMPA receptors to open. NMDA receptors are permeable to Ca2+,[18]which is an important cation in the nervous system[19] and has been linked to gene regulation.[20] The flow of Ca2+ through NMDA receptors is thought to cause both long-term potentiation (LTP, of synapse efficacy) and long-term depression (LTD) by transducing signaling cascades and regulating gene expression.
Metabotropic[edit]
Main article: Metabotropic glutamate receptor
Metabotropic glutamate receptors, which belong to subfamily C of G protein-coupled receptors are divided into three groups, with a total of eight subtypes (in mammals; this is not necessarily the case for most organisms). The mGluRs are composed of three distinct regions: the extracellular region, the transmembrane region, and the intracellular region.[21]The extracellular region is composed of a venus flytrap (VFT) module that binds glutamate,[22] and a cysteine-rich domain that is thought to play a role in transmitting the conformational change induced by ligand binding from in the VFT module to the transmembrane region.[21] The transmembrane region consists of seven transmembrane domains and connects the extracellular region to the intracellular region where G protein coupling occurs.[22] Glutamate binding to the extracellular region of an mGluR causes G proteins bound to the intracellular region to be phosphorylated, affecting multiple biochemical pathways and ion channels in the cell.[23] Because of this, mGluRs can both increase or decrease the excitability of the postsynaptic cell, thereby causing a wide range of physiological effects.
Outside the central nervous system[edit]
Glutamate receptors are thought to be responsible for the reception and transduction of umami taste stimuli. Taste receptors of the T1R family, belonging to the same class of GPCR as metabotropic glutamate receptors are involved. Additionally, the mGluRs, as well as ionotropic glutamate receptors in neural cells, have been found in taste buds and may contribute to the umami taste.[24] Numerous ionotropic glutamate receptor subunits are expressed by heart tissue, but their specific function is still unknown. Western blotsand northern blots confirmed the presence of iGluRs in cardiac tissue. Immunohistochemistry localized the iGluRs to cardiac nerve terminals, ganglia, conducting fibers, and some myocardiocytes.[25] Glutamate receptors are (as mentioned above) also expressed in pancreatic islet cells.[26] AMPA iGluRs modulate the secretion of insulin and glucagon in the pancreas, opening the possibility of treatment of diabetes via glutamate receptor antagonists.[27][28] Small unmyelinated sensory nerve terminals in the skin also express NMDA and non-NMDA receptors. Subcutaneous injections of receptor blockers in rats successfully analgesized skin from formalin-induced inflammation, raising possibilities of targeting peripheral glutamate receptors in the skin for pain treatment.[29]
Excitotoxicity[edit]
Overstimulation of glutamate receptors causes neurodegeneration and neuronal damage through a process called excitotoxicity. Excessive glutamate, or excitotoxins acting on the same glutamate receptors, overactivate glutamate receptors (specifically NMDARs), causing high levels of calcium ions (Ca2+) to influx into the postsynaptic cell.[34]
High Ca2+ concentrations activate a cascade of cell degradation processes involving proteases, lipases, nitric oxide synthase, and a number of enzymes that damage cell structures often to the point of cell death.[35] Ingestion of or exposure to excitotoxins that act on glutamate receptors can induce excitotoxicity and cause toxic effects on the central nervous system.[36] This becomes a problem for cells, as it feeds into a cycle of positive feedback cell death.
Glutamate excitotoxicity triggered by overstimulation of glutamate receptors also contributes to intracellular oxidative stress. Proximal glial cells use a cystine/glutamate antiporter (xCT) to transport cystine into the cell and glutamate out. Excessive extracellular glutamate concentrations reverse xCT, so glial cells no longer have enough cystine to synthesizeglutathione (GSH), an antioxidant.[37] Lack of GSH leads to more reactive oxygen species (ROSs) that damage and kill the glial cell, which then cannot reuptake and process extracellular glutamate.[38] This is another positive feedback in glutamate excitotoxicity. In addition, increased Ca2+ concentrations activate nitric oxide synthase (NOS) and the over-synthesis of nitric oxide (NO). High NO concentration damages mitochondria, leading to more energy depletion, and adds oxidative stress to the neuron as NO is a ROS.[39]
Neurodegeneration[edit]
In the case of traumatic brain injury or cerebral ischemia (e.g., cerebral infarction or hemorrhage), acute neurodegeneration caused by excitotoxicity may spread to proximal neurons through two processes. Hypoxia and hypoglycemia trigger bioenergetic failure; mitochondria stop producing ATP energy. Na+/K+-ATPase can no longer maintain sodium/potassium ion concentration gradients across the plasma membrane. Glutamate transporters (EAATs), which use the Na+/K+ gradient, reverse glutamate transport (efflux) in affected neurons and astrocytes, and depolarization increases downstream synaptic release of glutamate.[40] In addition, cell death via lysis or apoptosis releases cytoplasmic glutamate outside of the ruptured cell.[41] These two forms of glutamate release cause a continual domino effect of excitotoxic cell death and further increased extracellular glutamate concentrations.
Glutamate receptors' significance in excitotoxicity also links it to many neurogenerative diseases. Conditions such as exposure to excitotoxins, old age, congenital predisposition, and brain trauma can trigger glutamate receptor activation and ensuing excitotoxic neurodegeneration. This damage to the central nervous system propagates symptoms associated with a number of diseases.[42]"
God knows what my SLOTH has done to myself over the years...
ON A FINAL NOTE: I have noticed this phenomenon which occurs for me more notably as I age, or at least MORE NOTABLE. Its something that happens when the DIET is just right. And usually in a stage of flux between consuming heavy sugar for days, and either entering or exiting a low cal stage for a day or two, and regardless of on or off trt. But every now and then its like the stars align just right after some of the above,
and all of the sudden I had this LEAN & EMPOWERED sensation come over me for a few hours where I feel physically potent and pumped when I have not even been training in years.?!? Ironically, and for all I know, IT COULD EVEN BE DUE TO PERIODS where I have accidentally avoided glutens unknowingly. So there's a shout out to ya all ya Celiacs out there... LOL..
But there are just too many variables to even put a finger on it (as the last study/article suggests)...
AND NOW TAKING A MOMENT TO POINT OUT THAT I HAVE FELT TOO SELF-RIGHTEOUS ABOUT MY PRESENTATION HERE as of late and a problem that I have realized is encumbering me here. So I take a moment to RESET and REMIND all that if ANYONE finds my points sounding Conclusive in ANY WAY, then take that opportunity to CORRECT ME. If you feel I am so far off base from other perspective to even worry with, then PLUG A CLUE. WHATEVER....
THINK - That is the only goal..
The conclusion on every study to date regarding E2 & Libido has been the same. What is a scandal is the 'bro BS of the opposite.
