PreviouslyPreviously in Cell Bio

A) Fluid Mosaic Model

B) Cell Parts: Componentsand Organelles

C) Introduction to first case study Graves’ disease/ hyperthyroidism

TodaySignaling its roles in Graves’ disease

Thyroid activatorsOur 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?

Signaling typesUp close •Direct contact

•AutocrineThrough space

•Paracrine•Endocrine•Synaptic

PM receptorsGap junctionsSecreted ECM

Types of Extracellular Signaling

What types in thyroid regulation?Normal thyroid function

Endocrine signaling:(Intracellular receptorfor T4)

Endocrine signalingPM receptor

Negative feedback loop:What is it and why is it important?

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

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

Receptor characteristicsCharacteristics 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)

Types of Receptors

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?

Hypothesis : Thyroid being over-stimulated

Hypothesis: Mutation in signaling within cell leading increase in thyroid hormone production

Normal stimulation results from TSH/receptorinteraction

How does the thyroid know to react?How does a receptor provide specificity

Normal activation is the result of signal transductionsecond messenger cascade

How does signal transduction work?What could have gone wrong?

Testing the hypothesesIF hypothesis is true then what is expected?

What data would suggest the hypothesis needs to be revised?

Tonight: Research Symposium– Gallery 7=9pmNext week: How ‘normal’ signals get in

Lab: Analysis of complementationHow long does response to signal

‘normally’ last