Unit 6: Biochemistry of Hormones

Unit 6: Biochemistry of Hormones

Introduction to Hormones

Hormones are chemical messengers synthesized and secreted by specialized glands or cells, transported through the bloodstream to target organs, where they bind to specific receptors and elicit physiological responses. They regulate a wide range of processes including growth, development, metabolism, reproduction, and homeostasis.

Historical Perspective:

• The term "hormone" (from Greek "hormon" meaning "to set in motion") was coined by Ernest Starling in 1905.
• Early discoveries: Secretin (first hormone identified, 1902), insulin (1921), thyroid hormones, steroid hormones.

General Characteristics of Hormones:

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1. Chemical Classification of Hormones

Hormones are classified based on their chemical structure, which influences their synthesis, storage, secretion, transport, mechanism of action, and half-life.

1.1 Peptide/Protein Hormones

Examples:

1.2 Steroid Hormones

Classes of Steroid Hormones:

1.3 Amino Acid-Derived Hormones (Amines)

Examples:

1.4 Eicosanoid Hormones

Examples: Prostaglandins, thromboxanes, leukotrienes, prostacyclin (covered in Unit 4)

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2. Summary Table: Classification of Hormones by Chemical Structure

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3. Mechanisms of Hormone Action

3.1 Cell Surface Receptors (for Water-Soluble Hormones)

A. G Protein-Coupled Receptors (GPCRs) :

• Seven transmembrane domain receptors
• Activated hormone causes conformational change → G protein activation (exchange GDP for GTP on α subunit)
• G protein subunits (α, β, γ) regulate effector enzymes (adenylyl cyclase, phospholipase C)

Major Second Messenger Systems:

B. Tyrosine Kinase Receptors:

• Single transmembrane domain
• Ligand binding causes dimerization and autophosphorylation
• Phosphorylated tyrosines recruit signaling proteins (via SH2 domains)
• Activate Ras-MAPK pathway, PI3K-Akt pathway

Examples: Insulin, insulin-like growth factor (IGF-1), growth hormone (GH) – GH receptor uses JAK-STAT pathway (cytokine receptor family)

3.2 Intracellular Receptors (for Lipid-Soluble Hormones)

• Located in cytoplasm (steroid receptors) or nucleus (thyroid hormone receptors)
• Hormone diffuses across membrane, binds receptor → conformational change
• Hormone-receptor complex translocates to nucleus (if cytoplasmic)
• Binds to hormone response elements (HRE) on DNA
• Recruits coactivators/corepressors, regulates gene transcription
• Response time: Hours to days (requires protein synthesis)

Examples: Steroid hormones, thyroid hormones, vitamin D, retinoids

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4. Major Endocrine Glands and Their Hormones

4.1 Hypothalamus

The hypothalamus integrates neural and endocrine signals. It produces releasing and inhibiting hormones that regulate the anterior pituitary.

4.2 Pituitary Gland (Hypophysis)

A. Anterior Pituitary (Adenohypophysis) :

B. Posterior Pituitary (Neurohypophysis) :

4.3 Thyroid Gland

Thyroid Hormone Synthesis:

1. Iodide uptake (NIS symporter)
2. Oxidation to iodine (thyroperoxidase, TPO)
3. Iodination of tyrosine residues on thyroglobulin (MIT, DIT)
4. Coupling (MIT + DIT → T₃; DIT + DIT → T₄)
5. Proteolysis releases T₃/T₄ into blood

Transport: Bound to thyroxine-binding globulin (TBG), transthyretin, albumin; free fraction (0.03% T₄, 0.3% T₃) is active.

Peripheral conversion: T₄ → T₃ (more active) by deiodinases (selenoproteins).

4.4 Parathyroid Glands

4.5 Adrenal Glands

A. Adrenal Cortex (Zones) :

B. Adrenal Medulla :

4.6 Pancreatic Islets (Islets of Langerhans)

4.7 Gonads

A. Testes:

B. Ovaries:

4.8 Other Endocrine Tissues

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5. Hormonal Regulation and Feedback Mechanisms

5.1 Negative Feedback (Predominant)

• The response to a hormone inhibits further hormone secretion.
• Maintains homeostasis.

Examples:

• Thyroid axis: Low T₃/T₄ → increased TRH and TSH → increased T₃/T₄ production → high T₃/T₄ inhibit TRH and TSH.
• Cortisol: CRH → ACTH → cortisol → cortisol inhibits CRH and ACTH.
• Calcium: Low Ca → PTH → increases Ca → high Ca inhibits PTH.
• Glucose: High glucose → insulin → lowers glucose → low glucose inhibits insulin.

5.2 Positive Feedback (Less Common)

• The response to a hormone amplifies further hormone secretion.
• Creates a self-reinforcing cycle; usually terminated by an external event.

Examples:

• Oxytocin during labor: Uterine contractions stimulate oxytocin release, which strengthens contractions → further oxytocin release.
• LH surge before ovulation: Rising estradiol (late follicular phase) triggers a surge in LH (positive feedback) → ovulation.
• Platelet aggregation: Thromboxane A₂ promotes further platelet aggregation (local positive feedback).

5.3 Hierarchical Control (Endocrine Axes)

Hypothalamic-Pituitary Axis:

Hypothalamus (releasing/inhibiting hormones)
         ↓ (portal blood)
Anterior Pituitary (trophic hormones)
         ↓ (blood)
Peripheral Endocrine Gland (hormones)
         ↓
Target Tissues
         ↓
Feedback (usually negative) to Hypothalamus and Pituitary

Examples:

• Hypothalamic-Pituitary-Thyroid (HPT) axis
• Hypothalamic-Pituitary-Adrenal (HPA) axis
• Hypothalamic-Pituitary-Gonadal (HPG) axis

5.4 Circadian Rhythms

Many hormones exhibit daily rhythmic secretion:

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6. Pharmaceutical Importance of Hormones

Hormones and their analogs are extensively used in therapy for hormone deficiencies, as pharmacological agents to exploit their physiological actions, and as antagonists to block hormone action.

6.1 Hormone Replacement Therapy

6.2 Hormone Agonists and Antagonists

6.3 Hormone Analogs and Derivatives

6.4 Hormones as Diagnostic Tools

6.5 Hormones in Contraception

6.6 Hormones in Cancer Therapy

6.7 Hormones in Other Therapeutic Areas

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7. Summary Table: Major Hormones and Their Pharmaceutical Applications

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References

1. Lippincott Williams & Wilkins. (2020). Lippincott's illustrated reviews: Biochemistry. (Chapters on Hormones)

2. Berg, J. M., Tymoczko, J. L., & Gatto, G. J. (2019). Stryer's biochemistry (8th ed.). W. H. Freeman and Company. (Chapters on Signal Transduction and Hormones)

3. Nelson, D. L., & Cox, M. M. (2017). Lehninger principles of biochemistry (7th ed.). W. H. Freeman and Company. (Chapters on Hormonal Regulation and Signal Transduction)

4. Rodwell, V. W., Bender, D. A., Botham, K. M., Kennelly, P. J., & Weil, P. A. (2017). Harper's illustrated biochemistry (31st ed.). McGraw-Hill Education. (Chapters on Hormones and Endocrine Function)

5. Devlin, T. M. (2016). Textbook of biochemistry with clinical correlations (8th ed.). Wiley-Liss. (Chapters on Hormones and Their Actions)

6. Melmed, S., Auchus, R. J., Goldfine, A. B., Koenig, R. J., & Rosen, C. J. (2020). Williams textbook of endocrinology (14th ed.). Elsevier. (Comprehensive endocrinology reference)

7. Gardner, D. G., & Shoback, D. (2017). Greenspan's basic & clinical endocrinology (10th ed.). McGraw-Hill Education. (Clinical endocrinology)

8. Brunton, L. L., Hilal-Dandan, R., & Knollmann, B. C. (2017). Goodman & Gilman's: The pharmacological basis of therapeutics (13th ed.). McGraw-Hill Education. (Chapters on hormone therapy)

9. Katzung, B. G., & Vanderah, T. W. (2021). Basic & clinical pharmacology (15th ed.). McGraw-Hill Education. (Chapters on endocrine pharmacology)

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Recommended Textbooks for Further Reading:

• Lippincott Williams & Wilkins. (2020). Lippincott's illustrated reviews: Biochemistry. (Excellent for visual summaries and clinical notes on hormones)
• Melmed, S., et al. (2020). Williams textbook of endocrinology (14th ed.). (Comprehensive clinical resource)
• Gardner, D. G., & Shoback, D. (2017). Greenspan's basic & clinical endocrinology (10th ed.). (Concise clinical endocrinology)