Tissue selectivity is the ability of a drug or compound to activate receptors in some tissues while avoiding others. With SARMs, this means switching on muscle- and bone-building signals without strongly activating androgenic pathways in the prostate, skin, or hair follicles.
SARMs are designed to bind the androgen receptor (AR) in a way that creates a different downstream response depending on the tissue. Two key things make this possible:
1. Different AR shapes in different tissues
Co-regulators (co-activators and co-repressors) vary between muscles, bone, prostate, liver, etc. SARMs exploit these differences.
A molecule like Ostarine or RAD-140 can bind the same receptor but produce a muscle-dominant signal, not a full androgenic one.
2. Modulation, not full activation
Unlike testosterone, which is a full agonist (basically “all gas, no brakes”), SARMs act as partial agonists. They activate anabolic pathways, but their androgenic “side” is muted.
Or as one pharmacologist put it:
“SARMs don’t just bind the receptor – they change the conversation happening inside the cell.”
How SARMs Achieve Tissue Selectivity (Mechanism Breakdown)
1. Unique ligand-receptor shape changes
When a SARM binds to the androgen receptor, it changes its shape (conformation). This shape determines which genes get turned on or off.
In muscle: more co-activators → stronger anabolic signalling
In prostate/skin: fewer co-activators → weaker androgenic signalling
2. No conversion into DHT or estrogen
Most SARMs aren’t substrates for 5-α-reductase or aromatase. That removes two major androgenic amplification paths.
3. Tissue-specific recruitment of co-factors
For example:
RAD-140 strongly recruits anabolic co-activators in skeletal muscle
LGD-4033 is biased toward bone and muscle gene expression
Every SARM has its own selectivity fingerprint, which shapes its anabolic/androgenic balance.
FAQ
Is tissue selectivity why SARMs don’t convert to DHT? Partly. Most SARMs simply aren’t substrates for the enzymes that convert hormones into DHT or estrogen.
Does tissue selectivity mean SARMs won’t affect the prostate? Not zero impact – just far less than testosterone at equivalent anabolic doses.
Do all SARMs have the same tissue-selective profile? No. Each compound recruits different co-activators, so profiles vary dramatically.
Is tissue selectivity proven in humans? It’s supported by early clinical trials, but full long-term human datasets are limited.
Ever wondered what a “ligand” actually is when people talk about SARMs?You’ll see the word tossed around in studies, forums, and product descriptions – but what does it really mean? Let’s break it down in simple, science-backed terms.Spoiler: understanding ligands is key to understanding how SARMs work. What Is a Ligand? A ligand is simply …
Androgen Receptor (AR) Definition:The androgen receptor (AR) is a type of nuclear receptor – a protein found inside cells that binds to androgens, the body’s natural male sex hormones such as testosterone and dihydrotestosterone (DHT). Once activated, it moves into the cell nucleus and switches on genes responsible for muscle growth, strength, and sexual development. …
Heard the term “PPARδ agonist” thrown around in fitness circles or SARMs forums?Usually in the same sentence as Cardarine (GW-501516)? You’re not alone. It sounds complex – but understanding this one term can help you grasp exactly how compounds like GW-501516 work to boost endurance and fat metabolism. Let’s break it down. What Is a …
SERMs are a class of compounds that selectively bind to estrogen receptors, acting as either agonists or antagonists depending on the tissue type. They’ve been widely used in medicine – and more recently studied in performance and hormone-related contexts. But what exactly are SERMs, and how do they differ from SARMs or anabolic steroids? What …
Hurry while stocks last! Use code PAYDAY15 at checkout to get 15% off sitewide. Valid for
Glossary: Tissue Selectivity
What Is Tissue Selectivity? (Simple Definition)
Tissue selectivity is the ability of a drug or compound to activate receptors in some tissues while avoiding others.
With SARMs, this means switching on muscle- and bone-building signals without strongly activating androgenic pathways in the prostate, skin, or hair follicles.
It’s the core scientific reason SARMs exist.
Why Tissue Selectivity Matters in SARMs
SARMs are designed to bind the androgen receptor (AR) in a way that creates a different downstream response depending on the tissue.
Two key things make this possible:
1. Different AR shapes in different tissues
Co-regulators (co-activators and co-repressors) vary between muscles, bone, prostate, liver, etc.
SARMs exploit these differences.
A molecule like Ostarine or RAD-140 can bind the same receptor but produce a muscle-dominant signal, not a full androgenic one.
2. Modulation, not full activation
Unlike testosterone, which is a full agonist (basically “all gas, no brakes”), SARMs act as partial agonists.
They activate anabolic pathways, but their androgenic “side” is muted.
Or as one pharmacologist put it:
How SARMs Achieve Tissue Selectivity (Mechanism Breakdown)
1. Unique ligand-receptor shape changes
When a SARM binds to the androgen receptor, it changes its shape (conformation).
This shape determines which genes get turned on or off.
2. No conversion into DHT or estrogen
Most SARMs aren’t substrates for 5-α-reductase or aromatase.
That removes two major androgenic amplification paths.
3. Tissue-specific recruitment of co-factors
For example:
This is why each SARM feels slightly different: their selectivity profiles are not identical.
Further reading: Ostarine Mechanism of Action
Tissue Selectivity vs “Safety” – What Researchers Actually Mean
Tissue selectivity reduces – but does not eliminate – risks.
Researchers talk about:
But the keyword is reduced, not zero.
Why People Confuse Tissue Selectivity with Being ‘Side-Effect-Free’
SARMs gained popularity because early papers described them as “tissue-selective anabolic agents.”
People saw selective and assumed risk-free.
Reddit in 2025 summarises it perfectly:
Selectivity is dose-dependent, and once the receptor is saturated, androgenic pathways inevitably increase.
Further reading: Ostarine & SARMs side effects
Examples of Tissue Selectivity in Popular SARMs
Ostarine (MK-2866)
RAD-140
LGD-4033
Each SARM has its own “selectivity fingerprint.”
Why Tissue Selectivity Is Central to SARMs Research
Because the entire category was created to solve this equation:
Anabolic benefits − Androgenic side effects = Tissue-selective modulation
Every modern SARM trial still evaluates:
It’s the yardstick for determining whether a compound “does what SARMs are supposed to do.”
Core reading: What effects do SARMs have on the liver?
Key Takeaways
FAQ
Partly. Most SARMs simply aren’t substrates for the enzymes that convert hormones into DHT or estrogen.
Not zero impact – just far less than testosterone at equivalent anabolic doses.
No. Each compound recruits different co-activators, so profiles vary dramatically.
It’s supported by early clinical trials, but full long-term human datasets are limited.
Related Posts
Glossary: Ligand – What It Means In SARMs Research
Ever wondered what a “ligand” actually is when people talk about SARMs?You’ll see the word tossed around in studies, forums, and product descriptions – but what does it really mean? Let’s break it down in simple, science-backed terms.Spoiler: understanding ligands is key to understanding how SARMs work. What Is a Ligand? A ligand is simply …
Glossary: Androgen Receptor
Androgen Receptor (AR) Definition:The androgen receptor (AR) is a type of nuclear receptor – a protein found inside cells that binds to androgens, the body’s natural male sex hormones such as testosterone and dihydrotestosterone (DHT). Once activated, it moves into the cell nucleus and switches on genes responsible for muscle growth, strength, and sexual development. …
Glossary: PPARδ Agonist – What It Means
Heard the term “PPARδ agonist” thrown around in fitness circles or SARMs forums?Usually in the same sentence as Cardarine (GW-501516)? You’re not alone. It sounds complex – but understanding this one term can help you grasp exactly how compounds like GW-501516 work to boost endurance and fat metabolism. Let’s break it down. What Is a …
Glossary: SERMS
SERMs are a class of compounds that selectively bind to estrogen receptors, acting as either agonists or antagonists depending on the tissue type. They’ve been widely used in medicine – and more recently studied in performance and hormone-related contexts. But what exactly are SERMs, and how do they differ from SARMs or anabolic steroids? What …