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Dianabol Cycle

## Overview of Anabolic Steroids (Anabolic–androgenic Steroids, AAS)

| **Category** | **Key Points** |
|--------------|----------------|
| **What They Are** | Synthetic derivatives of the male sex hormone testosterone that can be taken orally or injected. Their primary purpose in medicine is to treat conditions such as delayed puberty, certain types of impotence, severe muscle wasting, and some hormonal deficiencies. |
| **How They Work** | They bind to androgen receptors inside cells, influencing gene expression and protein synthesis. This leads to increased muscle mass, red blood cell production (improving oxygen delivery), and changes in body composition. |
| **Common Medical Uses** | • Hormone replacement therapy for men with low testosterone
• Treatment of certain cancers that are hormone-sensitive (e.g., prostate cancer)
• Management of anemia via stimulation of erythropoiesis (sometimes combined with growth factors) |
| **Typical Dosing** | Varies widely by condition and formulation. For example, in hormone replacement therapy, doses might range from 50–200 mg daily orally for men, whereas for cancer treatment, intravenous or subcutaneous injections are used at doses calculated per kilogram of body weight. Precise dosing must be individualized under a physician’s guidance. |
| **Side Effects** | • Acne, oily skin
• Mood changes (euphoria or irritability)
• Fluid retention, edema
• Potential increase in blood pressure
• Rare but serious: thromboembolic events, liver enzyme elevations |

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## 2. How Is Testosterone Produced in the Body?

| Step | Key Organs & Cells | Hormones / Enzymes Involved |
|------|-------------------|-----------------------------|
| **1** | **Pituitary gland** releases **luteinizing hormone (LH)** | LH stimulates Leydig cells in testes |
| **2** | **Leydig cells** synthesize testosterone from cholesterol | Key enzymes: **SREBP-2**, **HMG-CoA reductase**, **CYP17A1**, **3β-HSD**, **5α-reductase** (type 1 & 2) |
| **3** | Testosterone circulates in bloodstream | Bound to SHBG or albumin; only free testosterone is biologically active |
| **4** | **Target tissues** uptake testosterone via diffusion or androgen receptors | Binding triggers genomic and non-genomic effects |

#### C. Testosterone Physiology: Synthesis, Transport, Metabolism

1. **Synthesis**:
- Primarily in Leydig cells (testis) for males; ovary/placenta/adrenal for females.
- Stimulated by LH via cAMP pathway.

2. **Transport**:
- Circulates as free testosterone (~0.3%), bound to SHBG (~10-15%) or albumin (~85%).
- Binding prevents renal excretion and maintains a reservoir.

3. **Metabolism**:
- Aromatization to estradiol via aromase (CYP19A1) in adipose tissue, brain.
- Reduction to dihydrotestosterone (DHT) by 5α-reductase in skin, prostate.
- Conjugation (glucuronidation, sulfation) for renal excretion.

4. **Regulation**:
- Negative feedback: high testosterone suppresses GnRH → LH/FSH secretion.
- Pulsatile release of GnRH required for LH/FSH; continuous stimulation leads to suppression.
- Stress hormones (cortisol, catecholamines) can alter gonadotropin release.

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## 4. Summary

| Aspect | Key Points |
|--------|------------|
| **Testosterone synthesis** | Cholesterol → pregnenolone → progesterone → 17‑OH‑progesterone → DHEA/DHEAS → androstenedione → testosterone (Leydig cells). |
| **Enzymes & genes** | CYP11A1, HSD3B2, CYP21A2, CYP17A1 (with POR), HSD17B3, AKR1C3; regulated by LHCGR, STAR, HSD10. |
| **Regulation** | LH → cAMP/PKA → up‑regulate steroidogenic enzymes and genes. |
| **Metabolism & transport** | 5α‑reductase (SRD5A1/2) → DHT; aromatase (CYP19A1) → estradiol; conjugation by UGTs; carriers: SHBG, albumin; elimination via liver and kidneys. |
| **Pathology** | Mutations in STAR, CYP11A1, HSD3B2, CYP17A1, SRD5A2 lead to congenital adrenal hyperplasia or disorders of sex development. |

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## 4. Suggested Further Reading

| Author(s) & Year | Title (Journal/Book) | Key Points |
|-------------------|----------------------|------------|
| **Klein and Kauffman** (2019) | *Steroid Hormone Biosynthesis and Function* – in \"Molecular Endocrinology\" | Comprehensive review of steroidogenic enzymes, regulation, and clinical disorders. |
| **Sullivan & Hines** (2020) | \"Enzymes of Steroidogenesis\" – *Endocrine Reviews* | Detailed enzymatic mechanisms, substrate specificity, and disease mutations. |
| **Roth et al.** (2018) | \"Steroidogenic Acute Regulatory Protein: A Key Regulator of Cholesterol Transport into Mitochondria\" – *Cell Metabolism* | Insight into StAR function and mitochondrial cholesterol handling. |
| **Ginsburg & Willerson** (2021) | \"Mitochondrial Pathways in Steroidogenesis\" – *Nature Reviews Molecular Cell Biology* | Integration of mitochondrial dynamics with steroid hormone production. |

These reviews provide comprehensive coverage of the enzymes, transport proteins, regulatory mechanisms, and their roles in adrenal physiology.

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### 4. Adrenal Cortical Function: Hormone Production, Regulation, and Pathophysiology

| **Hormone** | **Site of Production** | **Key Enzymes / Transporters** | **Regulation (Stimulation/Feedback)** | **Clinical Relevance** |
|-------------|------------------------|--------------------------------|---------------------------------------|------------------------|
| Cortisol | Zona fasciculata | 21-hydroxylase, 11β‑hydroxylase, CYP17A1 (17α‑hydroxylase) | ACTH ↑ → cortisol ↑; cortisol ↓ negative feedback to pituitary & hypothalamus | Cushing’s syndrome (excess), adrenal insufficiency (deficit) |
| Aldosterone | Zona glomerulosa | 21-hydroxylase, CYP11B2 (aldosterone synthase) | Angiotensin II ↑ → aldosterone ↑; potassium ↑ stimulates release; negative feedback via mineralocorticoid receptors | Conn’s syndrome (hyperaldosteronism), hyperkalemia |
| Cortisol | Zona fasciculata & reticularis | 21-hydroxylase, CYP11B1 (corticosteroid synthase) | ACTH ↑ → cortisol ↑; negative feedback via glucocorticoid receptors | Cushing’s syndrome, Addison’s disease |
| DHEA / DHEA‑S | Zona reticularis | HSD3B5 (3β‑hydroxysteroid dehydrogenase), CYP17A1 (17α‑hydroxylase/17,20‑lyase) | ACTH ↑ → adrenal androgen ↑; DHEA‑S synthesis occurs mainly in the liver | Hyperandrogenic disorders |

**Key Enzymes & Co‑factors**

| Enzyme | Reaction | Cofactor / Electron Donor |
|--------|----------|---------------------------|
| 3β‑Hydroxysteroid dehydrogenase (HSD3B1/HSD3B2) | Oxidation & isomerization of Δ⁴‑3β‑OH steroids to Δ⁵‑4-ketones | NAD⁺/NADP⁺ |
| Steroid 5α‑reductase type 1 & 2 (SRD5A1/SRD5A2) | Reduction of Δ⁴‑double bond | NADPH |
| Cytochrome P450scc (CYP11A1) | Side‑chain cleavage | FAD, FMN, cytochrome b₅ |
| 17α‑hydroxylase/17,20‑lyase (CYP17A1) | Hydroxylation & lyase activity | FAD, FMN, cytochrome b₅ |
| 21-hydroxylase (CYP21A2) | Hydroxylation at C21 | FAD, FMN, cytochrome b₅ |
| 11β‑hydroxylase (CYP11B1) | Hydroxylation at C11 | FAD, FMN, cytochrome b₅ |
| Aldosterone synthase (CYP11B2) | Oxidative steps for aldosterone | FAD, FMN, cytochrome b5 |

**Summary**

The steroidogenic pathway proceeds from cholesterol → pregnenolone → progesterone → 17‑hydroxyprogesterone → 11‑deoxycortisol → cortisol (or to corticosterone/aldosterone).
At each step the responsible P450 enzyme is listed, and the cofactors required for electron transfer are given.
The enzymes have distinct substrates and products, but share a common mechanism of transferring electrons from NADPH via cytochrome b5 reductase/cytochrome b5 to the heme iron of the P450 protein.

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