April 25, 2014 – Chemical signals and hormones I No pre-lecture quiz

1. April 25, 2014 – Chemical signals and hormones I • No pre-lecture quiz • Cell-to-cell signaling – an introduction • Endocrine systems & hormones • Case study: The importance of thyroid hormones (T3 & T4)

2. Introduction to chemical signals in animals – Major categories Endocrine cells may be organized into glands

3. Introduction to chemical signals in animals – Major categories Neurotransmitters

6. Endocrine systems are regulated by negative feedback Endocrine pathway Neuroendocrine pathway Neuroendocrine-to-endocrine pathway Stimulus Stimulus Stimulus Endocrine cell Sensor cell Sensor cell Endocrine signal Feedback inhibition Feedback inhibition Feedback inhibition Effector cell Neural signal Neural signal Response CNS CNS Neuroendocrine signal Neuroendocrine signal Effector cell Endocrine cell Endocrine signal Response Effector cell Response

7. Chemical characteristics of hormones – major classes Steroids Amino Acid Derivatives Peptides and Polypeptides Cortisol Secretin Epinephrine Receptor Receptor Not lipid soluble; bind to receptors on surface of target cell Most not lipid soluble; bind to receptors on surface of target cell Lipid soluble; bind to receptors inside target cell Receptor Target cell

8. Hormone Transport and Action on Target

9. Hydrophobic messengers pass into cell where they bind with transcription factors which affect gene expression.

10. Hydrophilic hormones bind to a receptor on the cell membrane which causes several reactions known as a signal transduction pathway. This can affect the properties of enzymes/proteins, etc. or it may affect gene expression.

11. This picture shows a hormone traveling through the cell membrane and binding with a transcription factor. Which of the following statements are true? A) This is a membrane soluble (hydrophobic) hormone that alters gene transcription. B) This is a membrane soluble (hydrophobic) hormone that alters immediate enzyme activity and cell processes. C) This is a membrane insoluble (hydrophilic) hormone that alters gene transcription. D) This is a membrane insoluble (hydrophilic) hormone that alters immediate enzyme activity and cell processes.

12. Barry Bonds was accused of using a steriod ‘the cream’ to increase his athletic performance. He supposedly applied this to his skin. What does this tell you about the nature of this hormone? A. The hormone was membrane insoluble. B. The hormone was membrane soluble. C. The hormone initiated a signal transduction pathway. D. A and C

13. Major endocrine glands Polypeptides Amino acid derivatives Steroids

14. Hypothalamus Growth-hormone-releasing hormone: stimulates release of GH from pituitary gland Corticotropin-releasing hormone (CRH): stimulates release of ACTH from pituitary gland Thyroid-releasing hormone: stimulates release of TSH from thyroid gland Gonadotropin-releasing hormone: stimulates release of FSH and LH from pituitary gland Figure 47-3-1 Antidiuretic hormone (ADH): promotes reabsorption of H2O by kidneys Oxytocin: induces labor and milk release from mammary glands in females Polypeptides Amino acid derivatives Steroids

15. Polypeptides Amino acid derivatives Steroids Pituitary gland Growth hormone (GH): stimulates growth Adrenocorticotropic hormone (ACTH): stimulates adrenal glands to secrete glucocorticoids Figure 47-3-3 Thyroid-stimulating hormone (TSH): stimulates thyroid gland to secrete thyroxine Follicle-stimulating hormone (FSH) and luteinizing hormone (LH):involved in production of sex hormones; regulate menstrual cycle in females Prolactin: stimulates mammary gland growth and milk production in females

16. Polypeptides Amino acid derivatives Steroids Figure 47-3-2 Thyroid gland Thyroxine:increases metabolic rate and heart rate; promotes growth Adrenal glands Epinephrine:produces many effects related to short-term stress response Cortisol:produces many effects related to short-term and long-term stress responses Aldosterone:increases reabsorption of Na+ by kidneys Kidneys Erythropoietin (EPO):increases synthesis of red blood cells Vitamin D:decreases blood Ca2+ Testes (in males) Testosterone:regulates development and maintenance of secondary sex characteristics in males; other effects

17. Polypeptides Amino acid derivatives Steroids Figure 47-3-4 Parathyroid glands Parathyroid hormone (PTH): increases blood Ca2+ Pancreas (islets of Langerhans) Insulin: decreases blood glucose Glucagon: increases blood glucose Ovaries (in females) Estradiol: regulates development and maintenance of secondary sex characteristics in females; other effects Progesterone:prepares uterus for pregnancy

18. Thyroid Hormone Thyroid hormone: - Actually two hormones (T3/T4) Mammals mainly secrete T4 - but some T4 is converted under certain circumstances - Same receptor binds both, but ↑affinity for T3 T3/T4 are membrane soluble - ↑metabolism in muscles, heart, liver & kidney T4 T3

21. Thyroid Gland

22. Low levels of iodine cause ~90% of goiters. Why?

23. T3 T3 Figure 47-8 Juvenile frog (tadpole) Adult frog Locomotion Tailless; walk or hop Locomotion Swim via movements of muscular tail Respiration Gas exchange occurs across skin, and in lungs Respiration Gas exchange occurs in gills, across skin, and in lungs Nutrition Nutrition Most are herbivorous; have a long gut specialized for digesting algae and plants Most are carnivorous; have a large mouth or long tongue for catching prey; short gut specialized for digesting proteins Excretion Most nitrogenous wastes excreted as ammonia Most nitrogenous wastes excreted as urea Excretion

24. Researchers figured out that tadpoles could be induced to undergo metamorphosis by feeding them ground up thyroid glands from horses. • They could also prevent metamorphosis by surgically removing the tadpoles' thyroid glands. • In juvenile amphibians, cells respond to increased levels of T3 in one of three ways: (1) They may begin growing and form new structures, such as legs; (2) They may die, as in cells that form the tadpole's tail; or (3) They may change structure and function.

25. Researchers figured out that tadpoles could be induced to undergo metamorphosis by feeding them ground up thyroid glands from horses. • They could also prevent metamorphosis by surgically removing the tadpoles' thyroid glands. • In juvenile amphibians, cells respond to increased levels of T3 in one of three ways: (1) They may begin growing and form new structures, such as legs; (2) They may die, as in cells that form the tadpole's tail; or (3) They may change structure and function. Take home message: The same hormone can multiple physiological effects

26. Anadromous versus Resident Stream Sticklebacks Higher metabolic rates Migrate from ocean to freshwater to breed Bigger Lower metabolic rates Permanent residents in freshwater Smaller

27. Anadromous versus Resident Stream Sticklebacks Higher metabolic rates Migrate from ocean to freshwater to breed Bigger Lower metabolic rates Permanent residents in freshwater Smaller I-Clicker - Which one has higher levels of thyroid hormone? A) Marine B) Stream

28. Kitano, J. et al. 2010. Adaptive divergence in the thyroid signaling pathway in the stickleback radiation. Current Biology 20:2124-2130. Marine Stream

29. Does T4 really affect metabolism? Experiment: For both marine and stream fish . . . 1. Expose some to higher levels of thyroid (T4) 2. Some unmanipulated (control) 3. Expose some to a thyroid inhibitor Measure Oxygen Consumption.

30. Does T4 really affect metabolism? Experiment: For both marine and stream fish . . . 1. Expose some to higher levels of thyroid (T4) 2. Some unmanipulated (control) 3. Expose some to a thyroid inhibitor Measure Oxygen Consumption in both marine and freshwater fish. What are the predictions?

31. Does T4 really affect metabolism? Experiment: Expose some to higher levels of thyroid (T4) Some unmanipulated (control) Expose some to a thyroid inhibitor

32. Does T4 really affect metabolism? Elevated T4 levels in marine fish were associated with upregulationof genes involved in aerobic metabolism (OXPHOS)

33. There are lots of other elements of the fish that differ, possibly due to thyroid hormone. -initiation of migration (for marine fish) -activity levels

34. There are lots of other elements of the fish that differ, possibly due to thyroid hormone. -initiation of migration -activity levels -DNA polymorphisms in binding sites of TSH

35. Altering individual behaviors by altering overall thyroid levels seems like a pretty blunt way to go about changing specific phenotypes. How could this system befine-tuned to optimize specific traits under different contexts? A.) changes in TRH expression B.) changes in TSH expression C.) alterations of TSH receptors D.) alteration of T3/T4 receptors in specific cell types.