Module 4.5

Cells use signaling molecules to coordinate functions.
Focus on hormones as signaling molecules:
- Hydrophobic Signaling Molecules: E.g., cortisol
- Bind to receptors inside the cell.
- Activate existing proteins and affect new protein production.
- Hydrophilic Signaling Molecules: E.g., growth hormone
- Bind to receptors in the cell membrane.
- Activate signaling pathways via secondary messengers.
Multiple signaling molecules can influence the same pathway, integrating signals for cellular response.
The lesson will analyze signals impacting bone growth.

Achondroplasia: A growth pattern where long bones stop growing prematurely.
- Occurs in the epiphysial plate where cartilage cells grow/divide.
- Signaling molecules from various glands influence this growth.
Focus on two key signaling molecules: Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1).

Secreted by the pituitary gland, situated in the brain.
Travels through the bloodstream and reaches the epiphysial plate.
Binds to receptors on cartilage cells, stimulating:
- Production of proteins that promote cell growth/division.
- Production of IGF-1 by cartilage cells.

IGF-1 is secreted from cartilage cells in response to GH.
IGF-1 molecules exit the cell to bind to receptors on other cartilage cells, amplifying growth responses.
GH can also act on liver cells:
- Liver cells secrete IGF-1 in response to GH in the bloodstream.

The total amount of GH and IGF-1 binding to a cell's receptors dictates cellular growth/division speed.
Cell response depends on activation of three kinase signaling pathways, specifically involving JAK2.

Variation in growth observed in dogs born on the same day by the same mother could be linked to GH production levels.
A scenario where an animal produces less GH leads to:
- Many GH receptors inactive, resulting in fewer active JAK2 kinases.
- Reduced phosphorylation of proteins, leading to decreased cell growth and increased cell death.
Eventually, cartilage cells die, stopping bone growth.

Animal studies demonstrate the impact of GH concentration:
- Mice Variations:
1. Normal GH concentration.
2. Defective gene reducing GH.
3. Defective gene with synthetic GH injections.
- Results:
- Mice with reduced GH were less than half the size of normal mice.
- Synthetic GH allowed growth closer to normal size.
Genetic influence also explored in mice missing GH receptors:
- Cells with non-functional receptors cannot respond to GH, affecting IGF-1 release.

IGF-1 and GH significantly impact growth, but:
- Both liver and cartilage cells need GH for IGF-1 release.
- A lack in GH concentration reduces IGF-1 levels, impairing further growth.

Cells integrate signals from both hormones through either pathway labeled X or Y.
- Both pathways: one ending with ERK and the other with AKT.
- Presence of both hormones implies an amplified response compared to having only one.

Four types of genetically engineered mice were studied:
1. Mice with normal GH and IGF-1 levels.
2. Mice lacking GH receptors.
3. Mice lacking IGF-1.
4. Mice lacking both GH receptors and IGF-1.
Expected growth outcomes:
- Mice without genetic alterations will grow normally.
- Mice lacking both IGF-1 and GH receptors will lack growth responses and be the smallest.
- Mice lacking IGF-1 will respond to GH but can't release IGF-1, having mid-range growth.
- Mice without GH receptors will have no response to GH and reduced IGF-1 levels derived from non-GH pathways, exhibiting limited growth.
Measurement results showed:
- Mice without IGF-1 and GH receptors had under 50% growth compared to normal mice.
- Mice with either one of the hormones showed intermediate growth.

Adjustments in protein activity and concentrations are dictated by signaling pathways.
Disruption of any pathway negatively impacts cellular structure and functions reliant on those signals.