Peptide hormones - mechanisms of action, function.

Peptide Hormones: Mechanisms of Action and Function

---

🔹 1. Overview: What Are Peptide Hormones?

Peptide hormones are polypeptides synthesized and secreted by endocrine glands. They regulate key physiological processes like metabolism, growth, reproduction, and homeostasis.

• Composed of 3 to over 100 amino acids
• Synthesized on ribosomes as preprohormones
• Stored in vesicles; released by regulated exocytosis

🔬 Example hormones: Insulin, Glucagon, ACTH, Parathyroid hormone (PTH), ADH, GH, FSH, LH

📚 Reference: Lehninger Ch. 23, Harper’s Ch. 42

---

🔸 2. Synthesis and Processing

🔬 Steps:

1. Preprohormone synthesis on rough ER
2. Cleavage of signal peptide → prohormone
3. Transport to Golgi and packaging into secretory granules
4. Final cleavage → active peptide hormone
5. Calcium-dependent exocytosis

🧪 Example: Proinsulin → C-peptide + Active Insulin (Insulin is stored in β-cell granules, released in response to glucose)

📚 Reference: Harper's Biochemistry, p. 501; NCBI Bookshelf - Endocrine Physiology

---

🔸 3. Mechanisms of Action

Peptide hormones cannot cross lipid membranes. They exert effects by binding to surface receptors, triggering intracellular cascades.

🔹 Receptor Types and Signaling Pathways:

A. G Protein-Coupled Receptors (GPCRs)

• Activate adenylyl cyclase → ↑ cAMP
• cAMP activates Protein Kinase A (PKA) → phosphorylates proteins

🧪 Example: Glucagon in hepatocytes stimulates glycogenolysis via cAMP

B. Phospholipase C (PLC) Pathway

• GPCR activates PLC → cleaves PIP₂ → DAG + IP₃
• IP₃ triggers Ca²⁺ release, DAG activates Protein Kinase C

🧪 Example: Oxytocin and vasopressin via IP₃/Ca²⁺ pathway

C. Receptor Tyrosine Kinases (RTKs)

• Ligand binding → receptor dimerization & autophosphorylation
• Recruits downstream proteins (e.g. IRS in insulin signaling)

🧪 Example: Insulin receptor (a tetrameric RTK)

D. JAK-STAT Pathway (for cytokine-type peptide hormones)

• Receptor recruits Janus Kinases (JAKs)
• JAKs phosphorylate STATs, which dimerize and enter nucleus to regulate gene transcription

🧪 Example: Growth hormone (GH) and prolactin

📚 References: Lehninger Ch. 12 (Signaling), Harper's Ch. 42; NCBI Book: Cell Signaling

---

🔸 4. Physiological Functions

Hormone	Origin	Target	Function
Insulin	β-cells (pancreas)	Muscle, fat, liver	↑ glucose uptake, ↓ blood glucose
Glucagon	α-cells	Liver	↑ glycogenolysis, gluconeogenesis
PTH	Parathyroid glands	Bone, kidney	↑ serum Ca²⁺ via bone resorption & reabsorption
GH	Anterior pituitary	Liver, bone, muscle	↑ IGF-1 production, tissue growth
FSH/LH	Anterior pituitary	Gonads	Gametogenesis, sex hormone synthesis
ADH (vasopressin)	Posterior pituitary	Kidney (collecting ducts)	↑ water reabsorption via aquaporin-2 insertion

📚 Source: Harper’s Biochemistry (2023); AccessMedicine

---

🔸 5. Clinical Relevance

Disorder	Defect
Type 1 Diabetes Mellitus	Autoimmune β-cell destruction → no insulin
SIADH (syndrome of inappropriate ADH)	Excess ADH → water retention, hyponatremia
Pseudohypoparathyroidism	Defective PTH receptor signaling (Gsα)
Laron Syndrome	GH receptor mutation → dwarfism (↓ IGF-1)

📚 Source: UpToDate; Robbins Pathologic Basis of Disease, 10th ed.

---

📚 References

1. Lehninger Principles of Biochemistry, 7th ed. – Chapters 12 & 23
2. Harper's Illustrated Biochemistry, 31st ed. – Chapter 42
3. NCBI Bookshelf – Endocrine Signaling Mechanisms https://www.ncbi.nlm.nih.gov/books/NBK542297/
4. AccessMedicine – Endocrine Physiology: Hormone Action & Regulation
5. UpToDate – Peptide Hormone Receptors and Clinical Disorders
6. PubMed ID 20478429 – Signaling Pathways of Peptide Hormones