Cellular Adaptations and Growth Control

Cellular Adaptations

• Cellular adaptations are adjustments cells make in response to changes in their environment.
• Objectives include describing cell signaling pathways, introducing the cell cycle, and focusing on adaptive responses in cell growth and differentiation.

Control of Cell Growth

• Cells in multicellular organisms communicate via chemical signals.
• Hormones act over long distances.
• Other local mediators act within the local environment (paracrine/autocrine).
• Some cells communicate directly through cell-cell contact.

Cell Signaling Molecules

• Hormones include insulin and cortisol.
• Local mediators include epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), TGFβ, cytokines (e.g., interferons, TNF).

Receptors

• Two main receptor types are important for cell growth: G-protein-linked receptors and enzyme-linked receptors.

G-protein-linked receptors

• Activate GTP-binding proteins (G-proteins).
• G-proteins are molecular switches.
• They remain active briefly while bound to GTP.
• They turn off by hydrolyzing GTP to GDP.

Enzyme-linked receptors

• Have intracellular domains with enzyme function.
• Mostly receptor tyrosine kinases.
• Activated by growth factors.
• Important in cell proliferation.
• Some activate small GTP-binding proteins like Ras, important in cancer.

The Cell Cycle

• Eukaryotic cell cycle consists of distinct phases, most dramatically nuclear (mitosis) and cytoplasmic (cytokinesis) division.
• M phase.
• Interphase: DNA replication, gene transcription, protein synthesis, and growth occur deceptively without major events.

Cell Cycle Control

• The restriction point (R point) at the end of G1 is the most critical checkpoint.
• Passage beyond R point depends on phosphorylation of the retinoblastoma protein (pRb).

Cell Populations

• Labile: Stem cells constantly divide to replenish losses (e.g., epithelial, hematopoietic cells). Often rapid proliferation.
• Stable: Cells rest in G0, but can divide when stimulated (e.g., hepatocytes, osteoblasts). Proliferate readily when necessary.
• Permanent: Cannot effectively proliferate in response to cell loss (e.g., neurons, cardiac myocytes).

Growth and Differentiation Responses

• Hyperplasia: Increased cell number in a tissue or organ, often from increased functional demand.
• Hypertrophy: Increased cell size leading to enlarged tissue/organ. Usually occurs when cell division capacity is limited.
• Atrophy: Decreased cell size and/or tissue/organ mass. Caused by reduced workload, loss of innervation, decreased blood supply, inadequate nutrition, or aging.
• Metaplasia: Reversible change where one differentiated cell type is replaced by another (e.g., squamous metaplasia in the respiratory tract of smokers).

Hyperplasia Causes

• Physiological: Hormonal stimuli (e.g., breast development during pregnancy), compensatory growth following tissue loss (e.g., liver regeneration)
• Pathological: Excessive hormones/growth factors, often associated with cancer risk (e.g., prostate, endometrium).

Hypertrophy Causes

• Physiological: Hormonal stimulation, increased functional demand
• Pathological: Increased functional demand (e.g., cardiac hypertrophy due to hypertension).

Aplasia, Hypoplasia, Dysplasia

• Aplasia: Complete failure of tissue/organ development.
• Hypoplasia: Incomplete tissue/organ development.
• Dysplasia: Abnormal cell maturation within a tissue, often precursor to cancer.