WHY DHT DOES NOT AFFECT YOUR JAW
OVERVIEW
1. Glossary
2. Central Theme of The Thread
3. How the Mandible Grows and Why DHT Is Not Involved
3.1. Endochondral ossification at the condyle (longitudinal growth)
3.2. Intramembranous ossification via periosteal apposition (widening + angular definition)
4. SYNTHESIS
1. GLOSSARY
OVERVIEW
1. Glossary
2. Central Theme of The Thread
3. How the Mandible Grows and Why DHT Is Not Involved
3.1. Endochondral ossification at the condyle (longitudinal growth)
3.2. Intramembranous ossification via periosteal apposition (widening + angular definition)
4. SYNTHESIS
1. GLOSSARY
Term | Definition |
|---|---|
Androgen | A steroid hormone that binds the androgen receptor to promote masculine characteristics |
Testosterone (T) | The primary circulating androgen,serves as both a hormone and a prohormone |
Dihydrotestosterone (DHT) | A 5AR metabolite of testosterone, possesses 5x greater affinity for the androgen receptor |
5α-Reductase (5-AR) | A microsomal enzyme that catalyzes the irreversible conversion of testosterone to DHT |
SRD5A2 | The gene encoding Type 2 5AR expressed in prostate, genital skin and hair follicles |
Androgen Receptor (AR) | A nuclear transcription factor that upon ligand binding regulates gene expression |
Osteoblast | The bone forming cell, shit basically synthesizes collagen matrix and facilitates mineralization |
Osteogenesis | The process of bone tissue formation |
Periosteum | The dense connective tissue layer surrounding bone, contains osteoprogenitor cells |
Periosteal Apposition | Bone deposition on the external surface, mechanism by which bones widen and become more robust |
Mandibular Condyle | The articular surface of the mandible (a secondary growth center mediating endochondral ossification) |
Endochondral Ossification | Bone formation that replaces a cartilaginous template, governs condylar growth |
Intramembranous Ossification | Direct bone formation within mesenchymal tissue, governs appositional growth |
Chondrocyte | Cartilage cell, proliferates and produces cartilaginous matrix |
5α-Reductase Deficiency (5ARD) | A rare condition caused by SRD5A2 mutation. complete inability to convert T to DHT |
Ligand | A molecule that binds to a receptor |
Ligand Affinity | The strength of binding between a ligand and its receptor |
Transcriptome | The complete set of genes expressed in a cell or tissue |
COL1A1 | The gene encoding type I collagen, primary organic component of bone matrix |
RUNX2 | A master transcription factor for osteoblast differentiation |
IGF1 | Insulin like growth factor 1, a potent mitogen for bone and cartilage cells. Probably discussed here before. |
Somatotropic Axis | The growth hormone/IGF1 endocrine system. Synergizes with androgens to mediate skeletal growth |
Paracrine | Acting locally on nearby cells |
Intracrine | Acting within the same cell where synthesized |
Aromatase | The enzyme (CYP19A1) that converts testosterone to 17β-estradiol |
Estradiol (E2) | The primary estrogen, it mediates epiphyseal fusion (the growth plate closing) and skeletal maturation |
2. CENTRAL THEME OF THE THREAD
The masculinization or specifically the development of a masc mandible, prominent mental protuberance, squared gonions and a more prominent supraorbital ridge (supra) is caused by testosterone binding directly to the androgen receptor expressed on osteoblasts and chondrocytes. This process is entirely independent of 5AR mediated conversion to DHT
Why This Distinction Matters:
Retards think DHT is some kind of "super T". This shit is true at the receptor level (5x greater affinity, slower dissociation) but this increased potency is irrelevant in tissues that lack the enzymatic machinery to produce DHT. The presence of 5AR determines where DHT acts, simple. The mandible does not express 5AR at levels that is significant to us since we need our jaws to be MASCULINE. Therefore the ligand reaching the osteoblast nucleus is testosterone and testosterone is fully competent to initiate the required transcriptional program
The Corollary:
Reducing DHT by 5AR inhibition (whether by genetic deficiency or pharmacological intervention like Fin or Dut) does not fuck your jaw growth. The androgen signal in osseous tissue remains intact because testosterone concentrations are unchanged.
3. HOW THE MANDIBLE GROWS AND WHY DHT IS NOT INVOLVED
The mandible masculinizes through two processes:
1. Endochondral ossification at the condyle (longitudinal growth)
2. Intramembranous ossification via periosteal apposition (widening + angular definition)
Neither process requires DHT
The masculinization or specifically the development of a masc mandible, prominent mental protuberance, squared gonions and a more prominent supraorbital ridge (supra) is caused by testosterone binding directly to the androgen receptor expressed on osteoblasts and chondrocytes. This process is entirely independent of 5AR mediated conversion to DHT
Why This Distinction Matters:
Retards think DHT is some kind of "super T". This shit is true at the receptor level (5x greater affinity, slower dissociation) but this increased potency is irrelevant in tissues that lack the enzymatic machinery to produce DHT. The presence of 5AR determines where DHT acts, simple. The mandible does not express 5AR at levels that is significant to us since we need our jaws to be MASCULINE. Therefore the ligand reaching the osteoblast nucleus is testosterone and testosterone is fully competent to initiate the required transcriptional program
The Corollary:
Reducing DHT by 5AR inhibition (whether by genetic deficiency or pharmacological intervention like Fin or Dut) does not fuck your jaw growth. The androgen signal in osseous tissue remains intact because testosterone concentrations are unchanged.
3. HOW THE MANDIBLE GROWS AND WHY DHT IS NOT INVOLVED
The mandible masculinizes through two processes:
1. Endochondral ossification at the condyle (longitudinal growth)
2. Intramembranous ossification via periosteal apposition (widening + angular definition)
Neither process requires DHT
3.1. Endochondral ossification at the condyle (longitudinal growth)
The mandibular condyle is a secondary cartilaginous growth center. Unlike primary growth plates (in long bones and shit) the condylar cartilage is adaptive and responds to both endocrine signals + mechanical loading
The mandibular condyle is a secondary cartilaginous growth center. Unlike primary growth plates (in long bones and shit) the condylar cartilage is adaptive and responds to both endocrine signals + mechanical loading
What happens at a Cellular Level:
- Chondrocyte Proliferation: Chondrocytes in the condylar cartilage undergo mitotic division producing new cartilaginous matrix
- Matrix Production: Chondrocytes secrete type II collagen and proteoglycans forming a template for future bone
- Hypertrophy + Mineralization: Chondrocytes enlarge, alter their gene expression and initiate matrix mineralization
- Ossification: Osteoblasts invade the mineralized cartilage template depositing bone and replacing cartilage with osseous tissue
- Forward Projection: This process pushes the mandible downward and forward lengthening the lower face (what most of us actually want)
What Happens at the Hormonal Level:
1. Primary Driver: The somatotropic axis (GH and IGF1) is the MAIN regulator of condylar growth. Growth hormone stimulates local and hepatic IGF1 production. IGF1 acts directly on chondrocytes to promote proliferation2. Androgenic change: Testosterone kinda helps this axis by increasing the amplitude of GH pulses from the pituitary. This effect is controlled by androgen receptors in hypothalamic neurons and pituitary somatotrophs
3. Direct Chondrocyte Stimulation: Chondrocytes express the AR. Testosterone binds these receptors directly adn promotes chondrocyte survival and matrix synthesis
Why DHT Is Irrelevant
1. Chondrocytes (like osteoblasts) exhibit negligible 5AR expressionn2. The androgen receptor in condylar chondrocytes is occupied and activated by testosterone at normal concentrations
3. The 5ARD phenotype confirms that condylar growth proceeds normally without DHT (im pretty sure there is a study on this too)
3.2. Intramembranous ossification via periosteal apposition (widening + angular definition)
The widening of gonial angle and the development of the mental protuberance and the thickening of the supras occur by periosteal apposition, which is the deposition of new bone on the external surface by osteoblasts in the cambium layer of the periosteum
The widening of gonial angle and the development of the mental protuberance and the thickening of the supras occur by periosteal apposition, which is the deposition of new bone on the external surface by osteoblasts in the cambium layer of the periosteum
What happens at a Cellular Level:
- Osteoprogenitor Activation: Androgens stimulate the proliferation + differentiation of periosteal osteoprogenitor cells
- Collagen Synthesis: Differentiated osteoblasts synthesize and secrete type I collagen (encoded by COL1A1) forming the organic matrix (osteoid)
- Mineralization: Alkaline phosphatase (encoded by ALPL) hydrolyzes inhibitors of mineralization (hydroxyapatite crystals deposit within the collagen scaffold)
- Lamellar Bone Formation: The mineralized matrix is organized into lamellar bone which basically increases cortical thickness and overall bone diameter
When T binds the AR in an osteoblast nucleus it initiates a specific transcriptional program
| Gene | Function |
|---|---|
| COL1A1 | Encodes type I collagen, basically the primary structural protein of bone |
| RUNX2 | Master transcription factor |
| SPP1 (Osteopontin) | Matrix protein, it facilitates cell adhesion and mineralization |
| IGF1 | Local growth factor, stimulates osteoblast proliferation (autocrine/paracrine) |
| BGLAP (Osteocalcin) | Matrix protein, it regulates mineralization and glucose metabolism |
| ALPL (Alkaline Phosphatase) | Enzyme, it promotes mineralization by hydrolyzing pyrophosphate |
What Happens By Mechanical Loading as a YOUNGCEL:
Bone adapts to mechanical strain. Masticatory forces generate deformation within the mandible and osteoblasts sense this strain and deposit bone where it is needed to resist future loading. Androgens increase the sensitivity of osteoblasts to mechanical signals. As you guessed, this shit is controlled by T, NOT DHT.
Bone adapts to mechanical strain. Masticatory forces generate deformation within the mandible and osteoblasts sense this strain and deposit bone where it is needed to resist future loading. Androgens increase the sensitivity of osteoblasts to mechanical signals. As you guessed, this shit is controlled by T, NOT DHT.
Why DHT Is Irrelevant:
1. Osteoblasts do not express 5AR at physiologically significant levels2. The AR in periosteal osteoblasts is occupied and activated by testosterone
3. The transcriptional program outlined above is initiated by testosterone binding bcz DHT would produce the same program if present but it is not present because the enzyme to make it is absent
The Role of Estrogen:
Testosterone is aromatized to 17β-estradiol by the enzyme aromatase (CYP19A1)Estrogen's Role:
1. Mediates epiphyseal fusion (the closure of growth plates that rapes your height)
2. Regulates periosteal bone formation in coordination with androgens
3. Maintains bone mineral density (BMD)
4. SYNTHESIS
The Pathway of HOW yourr JAW becomes MASC:
The Pathway of HOW yourr JAW becomes MASC:
- Testicular testosterone rises during puberty and reaches 300-1000 ng/dL
- Testosterone diffuses into osteoblasts and chondrocytes of the mandible
- Testosterone binds the AR directly (5AR is absent so no conversion to DHT occurs)
- The ligand receptor complex translocates to the nucleus and binds androgen response elements
- Transcription is initiated of osteogenic genes: COL1A1, RUNX2, IGF1, SPP1, BGLAP, ALPL
- Osteoblasts synthesize collagen matrix and facilitate mineralization
- Chondrocytes proliferate at the condyle
- Periosteal apposition widens the ramus
- THE JAW IS NOW MASCULINE.
View attachment 41598_2024_57617_Fig4_HTML.webp
(shape variation in sexes)
THANK YOU FOR FUCKING READING ❤.
