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Decadurabolin Sustanon Y Winstrol Deca Durabolin Effet Secondaire
**Testosterone and dihydrotestosterone (DHT) – why we measure both**
| Aspect | Testosterone | Dihydrotestosterone |
|--------|--------------|---------------------|
| **What it is** | The primary circulating androgen in men; also the main precursor of many other steroids. | A more potent androgen that is produced from testosterone by 5‑α‑reductase (type 1 & 2). |
| **Potency** | ~10× less active than DHT at the classical androgen receptor. | ~3–10× stronger ligand for the androgen receptor; drives many "classic" androgenic effects. |
| **Key physiological roles** | • Drives spermatogenesis (via intratesticular testosterone)
• Regulates muscle, bone, and fat metabolism
• Influences libido & mood | • Modulates hair follicle growth & mini‑aturization
• Stimulates sebaceous gland activity
• Controls the development of male external genitalia (in utero) |
| **Clinical relevance** | • Testosterone deficiency → low sexual function, muscle wasting, bone loss.
• Exogenous testosterone therapy used to treat hypogonadism. | • Androgenetic alopecia: excess DHT leads to follicular mini‑aturization and hair loss.
• Acne vulgaris & seborrheic dermatitis may result from high local DHT activity. |
### 3.2 Key Take‑away
- **Testosterone** is the systemic hormone that governs sexual function, body composition, and bone health.
- **Dihydrotestosterone (DHT)** is a more potent derivative acting locally in tissues such as hair follicles and sebaceous glands; its overactivity causes androgenic alopecia and acne.
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## 4. The Pathway from Testosterone to DHT
| Step | Enzyme | Substrate | Product | Location (common sites) |
|------|--------|-----------|---------|--------------------------|
| **1** | **5α‑Reductase type 2 (SRD5A2)** | Testosterone | **Δ4,5‑dihydrotestosterone** (DHT) | Prostate epithelium, hair follicles, skin, liver |
| **2** | *Optional*: 3β‑HSD, 17β‑HSD | DHEA → Androstenedione → Testosterone → DHT | - | Liver, adrenal cortex, gonads |
**Key enzyme**: SRD5A2 (type II 5α‑reductase) is the sole isoenzyme that catalyzes the conversion of testosterone to DHT in the target tissues. The reaction reduces the double bond between C4 and C5 of the steroid nucleus.
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## 3. How Inhibitors Work
| Drug | Mechanism | Target Site | Key Points |
|------|-----------|-------------|------------|
| **Finasteride** (and its prodrug, dutasteride) | Competitive antagonist that binds to SRD5A2’s active site, blocking substrate access and thus preventing the reduction step. | Cytosolic enzyme inside target cells. | • 100 % inhibition of SRD5A2.
• Selective for SRD5A2; does not affect SRD5A1. |
| **Cimetidine** | Acts as a reversible competitive inhibitor by mimicking the substrate’s structure and occupying the active site, preventing normal enzymatic action. | Cytosolic enzyme inside target cells. | • Inhibits both SRD5A1 and SRD5A2 (non‑selective).
• Less potent than cimetidine for SRD5A2 but still effective at therapeutic concentrations. |
These drugs differ in potency, selectivity, and the extent to which they inhibit one or both isoforms of 5α‑reductase.
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## **3 – Proposed Research Strategy**
| **Objective** | **Approach / Key Experiments** | **Rationale** |
|---------------|---------------------------------|---------------|
| **A. Identify small‑molecule inhibitors that selectively block SRD5A2 (but not SRD5A1).** | 1. *In silico* screening of a diverse chemical library against the crystal structure of SRD5A2.
2. Virtual docking followed by ADMET filtering.
3. Purchase or synthesize top ~200 hits. | Computational pre‑selection saves time and cost; ensures structural relevance to SRD5A2 active site. |
| **B. Validate inhibitory activity in vitro** | 1. Reconstitute purified SRD5A2 (and SRD5A1) into proteoliposomes.
2. Measure conversion of testosterone → DHT using radiometric or LC‑MS assay.
3. Determine IC₅₀ for each compound against both enzymes; calculate selectivity index (IC₅₀(SRD5A1)/IC₅₀(SRD5A2)). | Direct measurement of catalytic inhibition; confirms enzyme specificity and potency. |
| **C. Identify promising candidates** | 1. Select compounds with IC₅₀ <100 nM against SRD5A2 and >10× selectivity over SRD5A1.
2. Perform preliminary ADMET screening (metabolic stability, CYP inhibition). | Filters out weak or non‑selective inhibitors; ensures drug‑likeness of leads. |
| **D. Structural validation** | 1. Co‑crystallize top candidates with SRD5A2 to confirm binding mode.
2. Use X‑ray data to refine SAR and guide further optimization. | Provides mechanistic insight, improves confidence in selectivity. |
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## Expected Outcomes & Impact
- **Validated chemical probes** for selective inhibition of SRD5A1 vs. SRD5A2, enabling dissection of their distinct physiological roles.
- **Lead compounds** with favorable potency and selectivity that can be advanced to preclinical safety profiling.
- A robust methodological framework transferable to other enzyme families requiring isoform‑specific modulation.
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Prepared by
Your Name – Research Associate, Pharmacology & Drug Discovery Laboratory.
Date: Insert Date
Gender: Female