INTRODUCTION TO DIHYDROTESTOSTERONE
OVERVIEW
1. GlossaryOVERVIEW
2. What is Dihydrotestosterone (DHT)?
3. Biosynthetic Pathway
4. 5α-Reductase Enzymes
5. DHT being paracrine/intracrine
6. WHY does the body use DHT?
7. DHT across lifespan
8. DHT v TESTOSTERONE: A Comparison
9. CONCLUSION
1. GLOSSARY
- This is if you want to know what certain terms that we will use here actually mean.
| TERM | DEFINITION |
|---|---|
| Androgen | A steroid hormone that promotes masculine characteristics |
| Testosterone | The primary male sex hormone |
| Dihydrotestosterone (DHT) | A metabolite of T, the most potent androgen |
| 5α-Reductase | The enzyme that converts T into DHT |
| SRD5A1/SRD5A2 | The genes encoding Type 1 and Type 2 5α-reductase (we will shorten it to 5AR) |
| Prohormone | A substance that is converted into a hormone |
| Ligand | A molecule that binds to a receptor |
| Androgen Receptor (AR) | The protein that androgens bind to inside cells |
| Paracrine | Acting locally on nearby cells |
| Intracrine | Acting within the same cell where synthesized |
| Affinity | The strength of binding between a molecule and its receptor |
| Potency | The biological effect per unit of hormone |
| Metabolite | A molecule produced during metabolism |
| Tissue-specific | Occurring only in certain tissues/cell types |
2. WHAT IS DIHYDROTESTOSTERONE?
Dihydrotestosterone is a 5α reduced metabolite of T. Basically it is testosterone with the double bond between the 4th and 5th carbon atoms reduced by the enzyme 5AR
DHT is the most potent naturally occurring androgen in humans. It binds the androgen receptor with APPROX 5 times greater affinity than testosterone and dissociates from the receptor more slowly (resulting in a stronger + more prolonged transcriptional signal)
BUT, potency does not equal ubiquity. DHT is not simply super T that acts everywhere according to retards on here. Its actions are constrained by the tissues in which it is produced.
3. BIOSYNTHETIC PATHWAY
The synthesis of DHT follows an irreversible pathway, which i'll show here -
Cholesterol to Pregnenolone to Progesterone to 17α Hydroxyprogesterone to Androstenedione to Testosterone and via 5AR to DHT
The committed step is the conversion of testosterone to DHT by 5AR, all of this was water but necessary to understand what actually happens.
4. 5α-REDUCTASE ENZYMES
Two distinct isoenzymes (for simplicity i will shorten them to T1 & T2 if used in future) catalyze this conversion encoded by separate genes with different tissue distributions
| Isoenzyme | Gene | Primary Tissue Expression | Optimal pH |
|---|---|---|---|
| Type 1 | SRD5A1 | Sebaceous glands, nongenital skin, liver, brain | Basic (8) |
| Type 2 | SRD5A2 | Prostate, seminal vesicles, epididymis, genital skin, hair follicles | Acidic (5.5) |
5. DHT BEING PARACRINE/INTRACRINE
DHT is not primarily a circulating hormone. It is synthesized locally in target tissues from circulating T. The DHT measured in serum is largely spillover in a way from these peripheral sites (it does not reflect the concentration within tissues)
The Paracrine Model:
- T travels through the bloodstream
- It diffuses into cells of specific tissues
- If that cell expresses 5AR, T is converted to DHT
- DHT binds ARs in that same cell or adjacent cells
- The signal is executed locally
6. WHY DOES THE BODY USE DHT?
You may ask, but Dextuh, If T already activates the androgen receptor why bother making a more potent version?
The answer is: Amplification and specialization.
In tissues requiring strong androgen signaling but where testosterone concentrations might be limiting, 5AR serves as a signal amplifier. The conversion of T to DHT ensures that the androgen receptor is fully occupied and maximally activated in tissues where this is functionally important.
Tissues that utilize this amplification are:
1. Prostate: DHT is imp for prostatic growth and function
2. Genitals: DHT affects virilization in utero
3. Hair follicles: DHT (scalp) causes androgenetic alopecia in some unfortunate retards
4. Sebaceous glands: DHT regulates sebum production
5. Genital skin: DHT promotes growth of the dick and ballsack during development
Tissues that do NOT utilize this amplification are:
1. Skeletal muscle: Testosterone acts directly
2. Bone: Testosterone acts directly
3. Kidney, liver etc.: Testosterone acts directly
The body uses DHT as a tissue specific amplifier and not as the universal androgen.
7. DHT ACROSS LIFESPAN
DHT concentrations fluctuate throughout human development (water).
| Life Stage | DHT Activity | Physiological Role |
|---|---|---|
| In uterocel (weeks 8 ish iirc) | High (T2) | Masculinization of external genitalia and formation of prostate, ballsack, dick |
| Childhoodcel | Very low | Hypogonadotropic state |
| Pubertycel | Rises with T | Development of body hair, beard growth, sebum production and prostatee matures |
| Adultcel | Stable (10% of T) | Maintenance of prostate, hair follicles, sebaceous glands |
| Oldcel | Declines | Parallels decline in testosterone |
8. DHT v TESTOSTERONE: A COMPARISON
| Property | Testosterone | DHT |
|---|---|---|
| Source | Balls (95%) and adrenals (5%) | Peripheral conversion from T |
| Circulating concentration as an adult | 300-1000 ng/dL | 30-100 ng/dL (10% of T as I said earlier) |
| AR binding affinity | Baseline (reference) | 5x higher |
| Dissociation rate from AR | Faster | Slower |
| Aromatizable to estrogen? | Yes (via aromatase) | No |
| 5A reducible? | Yes (to DHT) | No (already reduced lol) |
| Primary mode of action | Endocrine | Paracrine/Intracrine (see topic 5) |
| Tissue distribution of action | Ubiquitous | Restricted to 5AR expressing tissues |
9. CONCLUSION
Evolution has placed 5AR in specific locations to amplify androgen signaling where needed like the prostate for reproduction, the hair follicles for social/sexual signaling and the genital skin for development (dick, balls)
The error many DHTcopertards make is assuming that because DHT is potent where it acts, it must act everywhere. It does not. DHT's reach is limited by where 5AR expression is present.
AND NO IT DOES NOT AFFECT YOUR JAW, YOU UTTER RETARD. I will post about it some day else.
THANK YOU FOR FUCKING READING ❤.
but yeah your guide was good so I exceeded my limits to finish it
