The Science Behind Testosterone's Cell Interaction

Written by Ben Bunting: BA, PGCert. (Sport & Exercise Nutrition) // British Army Physical Training Instructor // S&C Coach.

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Testosterone plays an essential role in muscle growth, sexual function and cognitive changes as well as mood stabilization.

Furthermore, testosterone helps prevent anemia - anemia occurs when there are not enough red blood cells to supply the body - as well as helping maintain bone strength.

Testosterone travels through the bloodstream bound to two proteins; only its free and albumin-bound forms are biologically active.  

By binding to specific receptors, hormones can mediate cell changes. Despite the fact that hormones circulate in the body, they only affect the cells that have the receptors.

As men age, their levels gradually decline.

You can use Military Muscle to amplify your testosterone production and regulate growth hormone secretion.

Key Points: 

• Testosterone plays a crucial role in various bodily functions such as muscle growth, sexual function, and mood stabilization.
• Androgen receptors interact with hormones like testosterone to regulate gene expression and influence protein production.
• Cell surface receptors facilitate cellular responses through various mechanisms and subtypes.
• Intracellular receptors for steroid hormones act as transcription factors, affecting gene expression and long-term changes in cell activity.
• Testosterone must bind with androgen receptors in target cells to have an impact on various bodily functions.
• Growth hormone regulates glucose levels and has effects on target cells through different receptors.

Androgen Receptors

The androgen receptor (AR) is a nuclear transcription factor that acts as a DNA-binding protein to regulate gene expression.

It plays an essential role in male sexual characteristics like testicular growth, hair growth and libido; and also plays an integral part in female sexual, somatic and behavioral functions including breast growth promotion, acceleration of bone formation and regulation of body hair development.

ARs interact with hormones like testosterone or dihydrotestosterone at the surface of cells, inducing a conformational change that leads to dissociation of heat shock proteins, dimerization of ARs and transport from cytoplasm to nucleus.

Once there, AR binds with specific sequences of DNA known as hormone response elements whose activity alters gene activity in order to influence protein production.

As well as regulating gene transcription, ARs also influence protein turnover and cellular metabolism.

They can decrease protein degradation while increasing protein synthesis to mitigate oxidative stress and inhibit oxidative damage to tissues.

Furthermore, ARs promote new blood vessel formation, increase blood flow to tissues, break down fats more efficiently, increase muscle mass growth.

At variance with other steroid receptors, AR can have effects independent of gene transcription, including altering cell signaling pathways.

Androgen binding to AR may lead to activation and phosphorylation of the ERK pathway leading to increased protein synthesis as a result of activating this signaling route and activation of its downstream signaling mechanisms such as EIF2 phosphorylation.

Androgens can also have an effect on neurotransmitters such as dopamine, serotonin and gamma aminobutryic acid (GABA).

Androgens have shown to produce effects similar to anxiolytics when administered via tests like the rat burying behavior test and taste aversion model of anxiety as well as inhibit beta amyloid toxicity in cultured hippocampal neurons.

While androgen receptors (ARs) can be found throughout the brain, their highest concentration lies within the septum, an area associated with memory and learning.

Blocking ARs within this area was found to reduce sexual behaviors in rats, suggesting that its modulating power can act as a regulator of androgen-induced behavior.

Cell Surface Receptors

Cell-cell signaling occurs primarily when receptor proteins bind with small molecules known as ligands - hormones, neurotransmitters, cytokines or growth factors can all act as ligands - known as ligands.

Cell surface receptors usually consist of transmembrane proteins with an extracellular ligand-binding domain and hydrophobic section spanning across plasma membrane.

They then have cytoplasmic domains for signal transmission into cells; moreover many G protein-coupled receptors (GPCRs) activate intracellular events and biochemical pathways that eventually lead to cell response.

Cell surface receptors come in various subtypes that vary in terms of binding preferences, signal transmission capabilities, and mechanisms of action.

Some neurotransmitter and peptide hormone receptors act like ligand-gated ion channels that control ion flux across the plasma membrane; others, like those for testosterone and estradiol hormones act through intermediary mechanisms involving G proteins - G protein-coupled receptors are the largest family of cell surface receptors and play an array of roles within our bodies.

Ligand-gated ion channels (LGICs) are like pores in the plasma membrane that open and close according to ion concentration gradients across cell surfaces.

When ligands bind to receptors on cell surfaces, LGICs open and allow ions into or out of cells for various responses by way of GPCRs; other than that GPCRs signal through intracellular events by activating second messengers such as cAMP, cyclic AMP, diacylglycerol or calcium.

Not only can receptors facilitate cellular responses, but some receptors also directly alter transcription in target cells (known as intrinsic gene-controlling activity).

These intracellular receptors work through second messenger-mediated regulation of cytoplasmic protein kinases.

Intracellular receptors typically bind to small, hydrophobic compounds that can be carried to cell membranes by lipids; examples include estrogen and its metabolite testosterone.

Furthermore, intracellular receptors may bind and activate protein tyrosine kinases of their respective ligands to initiate intracellular signaling events that alter protein synthesis.

Intracellular Receptors

Receptor proteins that detect signaling molecules that enter cells are essential to effective communication within cells.

When binding of a signaling molecule with its receptor causes a conformational change to take place within that protein and trigger downstream effects within the cell including changes in gene expression.

Chemical signals can come from hormones, neurotransmitters, drugs or environmental factors like temperature and humidity - these signals are detected by receptors located either on cell surfaces or inside of their cytoplasm and nuclei and recognized by these receptors.

Intracellular receptors for steroid and thyroid hormones act as transcription factor proteins, stimulating or inhibiting specific genes within target cells to induce long-term changes in cell activity.

Lipophilic hormones like estrogen and testosterone tend to move easily across plasma membranes to reach their respective intracellular receptors; hydrophobic ligands for these intracellular receptors, such as those found in sexual hormones like testosterone or estradiol are typically lipophilic as well.

After binding to its ligand, the hormone-receptor complex translocates into the nucleus.

Once there, it binds directly to a gene's promoter region to either activate or suppress transcription - these responsive genes.

Hormone receptor complexes typically bind to DNA sites known as Hormone Response Elements (HREs).

Each HRE consists of six nucleotides in a palindromic sequence with two equal and opposite half sites that are separated by three variable nucleotides; its minimal consensus sequence for steroid receptors is 5'-AGAACAnnnTGTTCT-3'.

Steroid receptors possess an HRE-binding domain with high conservation. This cystein-rich central domain contains two zinc finger proteins capable of binding to DNA sequences that contain HREs, stabilizing them using helix-turn-helix structures.

The AR is one of a class of intracellular receptors responsible for regulating spermatogenesis, which relies on testosterone and other androgens for stimulation.

Studies have demonstrated that mutations to its ligand-binding pocket can impede its ability to interact with coactivators and affect gene transcription.

For instance, mutations at residues 727 and 866 of the AR ligand-binding domain have been linked with severe oligozoospermia among men with normal production rates of testosterone and LH levels, leading them to reduced binding with their receptor HRE and decreased responsiveness to androgens such as dihydrotestosterone stimulation.

Target Cells

Testosterone is a male reproductive sex hormone that affects various functions in your reproductive organs and other areas.

It regulates your cholesterol levels, bone density and muscle mass measurements, fat storage patterns and red blood cell production as well as playing an integral part in driving sexual desire and impacting on how your heart, brain, immune system and nervous system operate.

Most testosterone production occurs within your testicles although small amounts are also produced by your ovaries.

Those using synthetic testosterone (anabolic steroids) to increase muscle mass or alter their appearance risk serious side effects or long-term health issues including blood clots, prostate cancer or stroke.

In order to have any impact, testosterone must bind with androgen receptors located within target cells.

These androgen receptors are coded by an AR gene; depending on its number of CAG repeats in this gene will determine how responsive your cells are to circulating androgens.

Individuals with fewer CAG repeats are generally more sensitive, while those with more repeats experience decreased effects from them.

When testosterone binds with its receptor, androgen signals the cell to grow or replicate itself - an essential process in spermatogenesis, the process by which sperm are produced in testicles.

Unfortunately, cancerous prostate cells can sometimes take advantage of androgen receptor to grow out of control and form tumors.

Testosterone's actions can also be affected by its interaction with other hormones and substances.

In particular, some target cells convert testosterone to dihydrotestosterone (DHT), which binds more closely with its receptor than testosterone and has an androgenic (masculinizing) effect.

Hypogonadism, which is characterized by decreased testosterone and sperm production, may result from any one of a variety of conditions.

This can include:

• A lack of gonadotropin-releasing hormone in your hypothalamus due to Prader-Willi syndrome
• Hypopituitarism; damage, infection, injury or surgery to Leydig cells that causes decreased production
• Other medical problems which suppress gonadotropin-releasing hormone in your pituitary gland (hypopituitarism, for example); among many others.

Aging can also have an adverse impact on testosterone production; your testicles gradually produce less of it as you age.

An orchiectomy procedure may further lower testosterone levels.

Non-classical kinase activation pathway

A study suggests that despite the fact that classical and nonclassical kinase activation pathways are both active, the classical pathway affects only one type of cell. Inhibition of the nonclassical pathway blocks spermatogenesis in vivo.

However, the classical pathway remains functional in the body.

However, the findings of the study are still preliminary and further studies are needed to determine whether nonclassical T signaling is essential for sperm maturation and male fertility.

Testosterone activates both phosphorylated and total ERK, but not all cells in the body.

Nevertheless, the nonclassical pathway was confirmed in Sertoli cells in vivo.

Moreover, a dominant-negative form of the AR suppresses the expression of PSA-luciferase and does not affect testosterone-mediated increases in ERK phosphorylation.

Sertoli cells

While scientists have known for 70 years that testosterone is essential for male fertility, they still don't understand the exact mechanisms by which testosterone works to regulate different cells in the body.

For instance, they don't know whether Sertoli cells contain genes that are regulated by testosterone, or whether they lack the gene.

The results of these studies are still preliminary, but they will hopefully provide the intellectual resources needed to develop more effective treatments for sexual dysfunction and contraception.

While there is no conclusive answer to the question, scientists do know that men's immune systems are not as robust as women's.

This is because their bodies are unable to respond to vaccinations as well as women's. Men's blood is more prone to inflammation, while women's response is stronger. This may be due to differences in hormone levels between men and women. 

Growth hormones

Growth hormone is a protein that regulates glucose levels in the blood. It stimulates the liver to produce more glucose and suppresses the uptake of insulin.

However, it has been linked to diabetes due to its effect on the liver. There are two kinds of growth hormone receptors: one that binds outside the cell, and one that binds inside the cell.

Growth hormone binds to both sites simultaneously, resulting in direct effects on the target cells.

One of these receptors is found on fat cells, and growth hormones increase the fat cell's metabolism and suppress its ability to accumulate circulating lipids.

Earlier, growth hormone treatment lasted until the end of growth. It has also been linked to increased energy levels.

In addition, growth hormone helps reduce body fat, thereby contributing to muscle and bone development.

Hence, some growth hormone specialists may recommend lifelong treatment for patients with growth hormone deficiency.

Growing research has shown that 30-50% of adults with growth hormone deficiency experience fatigue, even if they have a normal body weight.

Testosterone

Testosterone is a primary androgen synthesized from cholesterol and other precursors in the testicles.

Its biological action depends on its interaction with other anabolic signaling pathways. Testosterone's biological effects depend on its ligand, the IGFBP-1 receptor, and the physiological stress experienced.

In addition, the KISS1 gene encodes a peptide known as kisspeptin. Kisspeptin is a 54-amino-acid peptide that is released from neurons in the arcuate nucleus and anteroventral periventricular nucleus.

While testosterone is required for male fertility, its action is largely unknown. Only recently have molecular mechanisms for its action been identified.

Several genes regulated by testosterone, but not all of them, have been identified in Sertoli cells.

Testosterone has a direct role in regulating the process of spermatogenesis. The study of this hormone will provide intellectual resources for the development of therapies and contraceptives.

Conclusion

Androgen receptors play an essential role in controlling gene expression and modulating physiological functions in both males and females.

Interacting with hormones to induce changes in gene activity, protein production, cellular metabolism and sexual characteristics such as muscle growth or neurotransmitter activity.