1. Previously Previously in Cell Bio A) Fluid Mosaic Model B) Cell Parts: Components and Organelles C) Introduction to first case study Graves’ disease/ hyperthyroidism Today Signaling its roles in Graves’ disease

2. Thyroid activators Our Case Study  Thyroid stimulation: Extracellular signaling and the receptors that mediate it ‘Activating’ Signals: Hypothalmus: Thyrotropin releasing hormone (TRH) Pituitary Gland Thyroid stimulating hormone (TSH) Thyroid T4 (thyroxine)T3 (triiodothyronine) How are they all coordinated?

3. Signaling types Up close Direct contact Autocrine Through space Paracrine Endocrine Synaptic PM receptors Gap junctions Secreted ECM Types of Extracellular Signaling

4. What types in thyroid regulation? Normal thyroid function Endocrine signaling: (Intracellular receptor for T4) Endocrine signaling PM receptor Negative feedback loop: What is it and why is it important?

5. Binding vs. Effector Specificity Increase in circulating thyroid hormone causes: Increase in secretion by sweat glands Increase in rate and force of heart contractions Decrease in muscle strength How can this happen? Symptoms in Graves’ Disease

6. Binding vs. effector specificity 2 Different cells make different receptors Same receptor/ligand complex may trigger different response in a different cell type Ligand needs to bind with receptor (Receptors and Ligands? What are they?) How can thyroid hormone cause different responses in different parts of the body? Differences between binding specificity and effector specificity

7. Receptor characteristics Characteristics of a receptor: What does it need to have to do its job? Ribbon diagram of Thyroid hormone bound to Thyroid hormone receptor Diagram of isoproterenol bound to B2 adrengergic receptor ( Fig20-1 Molecular Cell Biology)

8. Types of Receptors

10. What happens in Graves’? What’s different in a Grave’s disease patient? (hyperthyroidism=increased thyroid function) Patients have increased T3 and T4 in bloodstream HYPOTHESES? What might make a thyroid put in overtime?

11. Hypothesis : Thyroid being over-stimulated Hypothesis: Mutation in signaling within cell leading increase in thyroid hormone production Normal stimulation results from TSH/receptor interaction How does the thyroid know to react? How does a receptor provide specificity Normal activation is the result of signal transduction second messenger cascade How does signal transduction work? What could have gone wrong?

12. Testing the hypotheses IF hypothesis is true then what is expected? What data would suggest the hypothesis needs to be revised? Tonight: Research Symposium– Gallery 7=9pm Next week: How ‘normal’ signals get in Lab: Analysis of complementation How long does response to signal ‘normally’ last