Regulation

1. Regulation • Why are hormones needed? • chemical messages from one body part to another • communication needed to coordinate whole body • daily homeostasis & regulation of large scale changes • solute levels in blood • glucose, Ca++, salts, etc. • metabolism • growth • development • maturation • reproduction growth hormones

2. Regulation & Communication • Animals rely on 2 systems for regulation • endocrine system • system of ductless glands • secrete chemical signals directly into blood • chemical travels to target tissue • target cells have receptor proteins • slow, long-lasting response • nervous system • system of neurons • transmits “electrical” signal & release neurotransmitters to target tissue • fast, short-lasting response

3. Regulation by chemical messengers • Neurotransmitters released by neurons • Hormones release by endocrine glands endocrine gland neurotransmitter axon hormone carried by blood receptor proteins receptor proteins Lock & Keysystem target cell

4. Classes of Hormones • Protein-based hormones • polypeptides • small proteins: insulin, ADH • glycoproteins • large proteins + carbohydrate: FSH, LH • amines • modified amino acids: epinephrine, melatonin • Lipid-based hormones • steroids • modified cholesterol: sex hormones, aldosterone insulin

5. How do hormones act on target cells • Lipid-based hormones • hydrophobic & lipid-soluble • diffuse across cell membrane & enter cells • bind to receptor proteins in cytoplasm & nucleus • bind to DNA as transcription factors • turn on genes • Protein-based hormones • hydrophilic & not lipid soluble • can’t diffuse across cell membrane • bind to receptor proteins in cell membrane • trigger secondary messenger pathway • activate internal cellular response • enzyme action, uptake or secretion of molecules…

6. Action of lipid (steroid) hormones steroid hormone target cell blood S 1 S cross cell membrane protein carrier S 2 binds to receptor protein becomes transcription factor 5 S 3 plasma membrane 4 DNA mRNA 6 7 ex: secreted protein = growth factor (hair, bone, muscle, gametes)

7. Question #1 • Why would being non-polar allow steroid hormones to move through the cell membrane? When a substance is nonpolar, it can interact with / flow through other nonpolar things. The hydrophobic tails of the membrane’s phospholipids are nonpolar. Therefore, steroid hormones can move right through the cell membrane. B. What type of receptors would steroid hormones bind to (options = plasma membrane receptors or intracellular receptors)? Why? They would bind to intracellular receptors because it is able to pass through the cell membrane and move directly into the cell. Thus, they would bind to a intracellular receptor. Only signal molecules that cannot pass through the membrane bind to plasma membrane receptors.

8. signal-transduction pathway Action of protein hormones 1 signal proteinhormone plasma membrane P activates G-protein binds to receptor protein activates enzyme cAMP acts as 2° messenger ATP transduction GTP activatescytoplasmicsignal ATP activates enzyme 2 secondary messengersystem activates enzyme response 3 produces an action target cell

9. adrenal gland Ex: Action of epinephrine (adrenaline) signal 1 epinephrine activatesG protein 3 activatesadenylyl cyclase receptor protein in cell membrane cAMP GDP transduction 4 ATP 2 GTP activates protein kinase-A 5 activates GTP activates phosphorylase kinase cytoplasm releasedto blood activates glycogen phosphorylase 7 glycogen glucose 6 liver cell response

10. Question #2 Amines (ex: epinephrine): modified from the amino acid tyrosine ; they are water-soluble (aka polar) so they CANNOT pass through the cell membrane A. Why would being polar prevent amine hormones from moving through the cell membrane? • Polar and nonpolar substances do not mix or interact. Because the inside of the cell membrane is nonpolar, only nonpolar things can pass through it. Polar substances are repelled by the hydrophobic tails of the phospholipids. B. What type of receptors would amine hormones bind to? Why? They would bind to plasma receptor proteins since they cannot pass through the membrane to access the intracellular receptors (which are inside the cell).

11. Question #3 • Full Proteins or Single Polypeptides (ex: oxytocin… used to induce labor): vary in size ; they are water-soluble so they CANNOT pass through the cell membrane. A. Why would being water soluble (i.e. being attracted to water) prevent protein hormones from moving through the cell membrane? • If a substance is attracted to water, it is either charged or polar. Again, polar substances cannot interact/pass through nonpolar substances. This prevents protein hormones from passing through the hydrophobic membrane interior. B. What type of receptors would protein hormones bind to? Plasma membrane receptors for the reason stated in #2B above.

12. Question #4 Describe what is occurring in each of the six steps shown in the image to the left. • The hormone is passing through the cell membrane. • The hormone binds with an intracellular receptor. • The intracellular receptor protein is activated as a transcription factor and passes through the nuclear membrane. • The hormone-receptor complex transcribes a segment of DNA into mRNA. • The mRNA leaves the nuclear membrane. • A ribosome translates the mRNA into the desired protein.

13. Question #4 What type of hormone is being used? How do you know? • It must be a steroid since that is the only nonpolar hormone molecule, meaning that it can pass through the membrane and bind to an intracellular receptor. Which parts of the pathway shown in the image to the left represent reception, transduction and response? • Step 1 & 2= reception. Step 3, 4, & 5= transduction. Step 6 = response.

14. Describe how this image is different from the previous image. • The initial hormone cannot pass through the membrane, so it binds to a plasma membrane receptor rather than an intracellular receptor. What type of hormone is being used? How do you know? • It must either be an Amine or Protein hormone because it is polar/water-soluble and cannot pass through the cell membrane. Which parts of the pathway shown in the image to the left represent reception, transduction and response? • The triangle fitting into the membrane receptor is reception. The second messengers represent transduction. The transcription factor being activated would be considered the response.

15. Benefits of a 2° messenger system Amplification! 1 signal Activated adenylyl cyclase receptor protein Not yet activated 2 amplification 4 amplification 3 cAMP 5 amplification GTP G protein protein kinase 6 amplification enzyme Cascade multiplier! 7 amplification FAST response! product

16. Feedback Feedback is a property of all open systems.

17. Negative Feedback Negative feedback: any situation where the output of a process decreases the occurrence of that process. Regulatory in nature. Negative feedback maintains homeostasisof the system.

18. high low Maintaining homeostasis hormone 1 lowersbody condition gland specific body condition raisesbody condition gland Negative FeedbackModel hormone 2

19. pancreas high liver low pancreas liver Endocrine System Control Feedback Regulation of Blood Sugar islets of Langerhans beta islet cells insulin body cells takeup sugar from blood liver storesglycogen reducesappetite blood sugar level (90mg/100ml) liver releasesglucose triggershunger islets of Langerhansalpha islet cells glucagon

20. Question #5 In response to high blood glucose levels (ex: after a meal), your pancreas releases the hormone insulin into the bloodstream. Insulin causes liver cells to take in glycogen. In the liver cells, glucose molecules join together to form glycogen, a large energy-storage polysaccharide (i.e. big carbohydrate). Bringing glucose molecules into the liver cell to be stored causes blood glucose levels to drop. In response to low blood glucose levels (ex: if you haven’t eaten a meal in a while), your pancreas releases glucagon into the bloodstream. Glucagon causes glycogen in liver cells to be broken down into individual glucose molecules. These glucose molecules are released into the blood, thereby raising blood glucose levels. Is this system an example of positive or negative feedback? Explain your answer

21. Question #6 Diabetes is a disease in which there is an error in the blood glucose control system. There are two forms of diabetes—Type 1 diabetes and Type 2 diabetes A. With Type 1 diabetes, the pancreas cannot produce insulin. How will this affect blood glucose levels? B. With Type 2 diabetes, the pancreas can produce insulin, but the receptors on the liver cells that cause the liver cells to respond to insulin are dysfunctional. How will this affect blood glucose levels?

22. Are the hormones calcitonin and parathyroid hormone part of a negative or positive feedback loop? How do you know?   They are part of a negative feedback loop because the product inhibits / reduces / stops the initial stimulus. Initial stimulus = blood calcium too high,Response = Thyroid gland releases calcitonin,End Result = blood calcium lowers.The product of this feedback loop reduces the initial stimulus. Where does calcitonin store the excess calcium moved from the blood? In other words, what tissue in your body is primarily made of calcium?Bones Regulation of Blood Calcium

23. osmoreceptors inhypothalamus increasethirst nephron nephron high JuxtaGlomerularApparatus low nephron (JGA) adrenalgland Endocrine System Control Feedback Blood Osmolarity ADH increasedwaterreabsorption pituitary blood osmolarity blood pressure increasedwater & saltreabsorption angiotensin aldosterone

24. Ex. Operons in gene expression

25. Ex. Temperature Regulation in Mammals

26. Ex. Population Growth

27. Positive Feedback Positive feedback: any situation where the output of a process increases the occurrence of that process. Amplifying in nature. Positive feedback causes transformation in the system.

28. Ex. Animal Birth

29. Is the hormone oxytocin (involved in human labor) part of a negative or positive feedback loop? How do you know? Oxytocin is part of a positive feedback loop. Once the baby’s head pushes against the cervix, the pressure impulses are sent to the brain which then stimulates the release of oxytocin. Oxytocin then stimulates muscular (uterine) contractions which pushes the baby’s head farther down on the cervix. This cycle repeats. In a positive feedback loop, the product strengthens or reinforces the original stimulus.

30. Ex. Fruit Ripening

31. Question #7 A ripening apple releases the hormone ethylene. Nearby apples come in contact with the ethylene hormone and ripen in response. As they ripen, they release more ethylene. Is this system an example of positive or negative feedback? Explain your answer.

32. Question #8 What are the pros and cons of using the endocrine system as a method of cell signaling?

33. Nervous & Endocrine systems linked • Hypothalamus = “master nerve control center” • nervous system • receives information from nerves around body about internal conditions • releasing hormones: regulates release of hormones from pituitary • Pituitary gland = “master gland” • endocrine system • secretes broad rangeof “tropic” hormones regulating other glands in body hypothalamus posterior pituitary anterior

34. tropic hormones = target endocrine glands hypothalamus thyroid-stimulating hormone (TSH) antidiuretic hormone (ADH) posterior pituitary Thyroid gland anterior pituitary Kidney tubules adrenocorticotropic hormone (ACTH) oxytocin Muscles of uterus gonadotropic hormones: follicle- stimulating hormone (FSH) & luteinizing hormone (LH) melanocyte-stimulating hormone (MSH) growth hormone (GH) prolactin (PRL) Adrenal cortex Melanocyte in amphibian Mammary glands in mammals Bone and muscle Ovaries Testes

35. Any Questions?? Robert Wadlow 1918-1940 8' 11"