Endocrinology CH 17 January 25 The Big Question: How do cells communicate with each other in non-synaptic fashion to maintain homeostasis in a changing environment? What are hormones? What are the different classes of hormone? What makes hormones receptor specific? How do hormones change cellular function by directly binding DNA? How do hormones change cellular function by creating/destroying second messengers? What is the function of the adrenal gland? Endocrine assignment due in class today! 10 pts Last Content for 20 point quiz Monday Jan 28th.

How do cells and organs communicate with each other? Cells need to be able to modify the activity of each other. Methods of Information Delivery Differ: Synapse: (neurotransmitter) Blood Stream: (endocrine hormone) Endocrine Hormone: Non-synaptic chemical signal for another organ that is secreted into the blood stream. Chemical Types: steroid, amines, proteins, and lipids Hormones are synthesized, stored, and released into the tissue interstitium, then diffuse to target.

The three classes of hormone differ in regards to the degree of distribution in the body: 1) Endocrine: diffusion of hormone to/from blood (Wide Distribution, long-lived hormone). Adrenal Gland: EPI/NE, Aldosterone, Cortisol Pituitary Gland: ADH, Oxytocin, Growth Hormone Gonads: Estrogen, Testosterone Thyroid Gland: Thyroxine, Calcitonin 2) Paracrine: diffusion stays within a few cells distance of release site (Local action only). Prostaglandins= most promote injury/inflammation Prostacyclin= often provide cell health signal Nitric Oxide=dilate blood vessels in heart 3) Autocrine: acts on secreting cell itself (short-lived hormone). Endothelial cells make nitric oxide which also finds a receptor on same cell, this keeps healthy endothelium less permeable  Note: Some hormones can also be used as neurotransmitters: NE, EPI, NO, HIS

What determines how widely a hormone and its effects are distributed in the body? 1) Site of hormone release: 2) Amount of hormone released: 3) Water/Lipid solubility of hormone: 4) Cardiovascular function and transit time of blood through the heart and to all parts of body: 5) Degradation rate of hormone: Enzymatic degradation of hormone Oxidation of hormone Removal of hormone to urine Effect of diffusion on hormone concentration 6) Of course the target cell must express functional receptors for the specific hormone that is released!

BASICS: How do hormones create specific physiological changes and effects in their specific target cells? Why do some hormones (steroids) require transport proteins?

HORMONES CHANGE CELLULAR ACTIVITY IN FOUR WAYS! 4 Classic Ways Hormones Change Cellular Activity: 1) Thyroxine: Direct binding to DNA backbone so that mRNA transcription is modified. 2) Steroids: Indirect DNA binding through a nuclear-receptor protein that binds to DNA. (∆mRNA production) 3) Insulin: The plasma membrane receptor is a “kinase” in the cytosol that phosphorylates target proteins in cell. 4) Epinephrine and most other hormones modify cell via “2nd Messengers”: This is the most complicated but most frequently used, it is also very pharmacologically important. Second Messengers are chemicals created in the cell to translate change in receptor status to a change in cellular function. Second messengers change target protein functions within the cell, not the hormone itself.

Direct Action: Thyroxin (Tri and Tetraiodothyroxine contain iodine) and can bind specific sites on DNA. This changes the rate of transcription (DNA to mRNA) for specific genes to promote or inhibit the creation of selected proteins. T3: raises metabolic rate, generates heat and promotes growth! Steroids use a similar manner to change cell function

Insulin creates its effect by stimulating a Tyrosine Kinase.

MANY HORMONES release G-proteins to activate the enzyme phospholipase, which creates IP3 and diacylglycerol (DAG). These 2nd messengers (IP3 and DAG) bind selective intracellular targets and start a cascade of reactions inside the cell. Memorize!

Hormones can cause the release of a stimulatory G-protein that activates adenylyl cyclase (AC) which makes cyclic AMP (cAMP is a second messenger). AC Inhibition (inhibitory G-protein): hormones can inactivate AC stopping cAMP production and its cascade of effects. Memorize This Pathway!

cAMP (2nd messenger) is produced by adenylyl cyclase IF a Stimulatory G-Protein is Present and destroyed by the enzyme phosphodiesterase. What effect will the phosphodiesterase inhibitor caffeine have on the intracellular cAMP concentration?

Hormone structures can be very similar but the effects can be very different! For example: ADH and Oxytocin are peptides that differ by just 2 amino acids. ADH causes kidney to reabsorb H2O. Oxytocin causes uterus to contract! Receptors are extremely tissue and hormone specific!

Does a endocrine mimicking drugs: TRT for Allergies/Hypertension: Cellular responses to hormones/drugs can change. WHY IS THIS IMPORTANT???? Does a endocrine mimicking drugs: TRT for Allergies/Hypertension: Look/ Act like hormone: AGONIST (pseudoephdrine: alpha-1) Look/ NotAct like hormone: ANTAGONIST (prazosin: alpha-1) Dosage: Physiological vs. Pharmacological How much is created and how much is required for effect? Why might low level or high level hormone releases give different effects? Consider ADH effects with moderate or severe dehydration! Do two hormones work together or against each other? Synergistic (same) Effects: Oxytocin and Prostaglandins work together in uterus! Antagonistic (against) Effects: Glucagon vs. Insulin work against each other in liver!

Monday’s 20 pt quiz covers notes up to this point (CH17) Monday’s 20 pt quiz covers notes up to this point (CH17). Please bring scantron as shown below. Let the notes be your guide to lecture quiz content and let the book help guide you towards understanding. Quiz will be given during last 20 minutes of class, see practice quiz online to better understand quiz format, but do not use it as a “study guide”.

Practice Quiz : 1)True/False: Cyclic AMP is a hormone that is destroyed inside the cytosol by the enzyme adenylyl cyclase. 2) The hormone _______reduces sodium reabsorption in the kidney and blood pressure. a)Thymopoietin b)Aldosterone c)Angiotensin d)Nitric oxide e)None of above 3) Lung relaxes during stress to increase airflow into the lung in response to what adrenergic receptor? a) Beta1 b) Beta2 c) Beta2 d) Alpha1 e) Alpha2 f) Nicotinic g) Muscarinic 4) Which paracrine hormones would be most likely to be associated with causing your allergy symptoms? Arachidonic acids b) Prostacyclins c) Prostaglandins d) Leukotrienes 5) True/False: Your pineal gland probably secreted more melatonin this morning when you woke up before your alarm clock to come to class, if you didn’t get to class and fell back asleep.