April 25, 2014 – Chemical signals and hormones I 1.No pre-lecture quiz 2.Cell-to-cell signaling – an introduction 3.Endocrine systems & hormones 4.Case study: The importance of thyroid hormones (T3 & T4)

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

Neurotransmitters Introduction to chemical signals in animals – Major categories

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

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

Hormone Transport and Action on Target

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

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.

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.

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

Steroids Polypeptides Amino acid derivatives Major endocrine glands

Figure Hypothalamus Growth-hormone-releasing hormone: stimulates release of GH from pituitary gland Corticotropin-releasing hormone (CRH): stimulates release of ACTH from pituitary gland Gonadotropin-releasing hormone: stimulates release of FSH and LH from pituitary gland Thyroid-releasing hormone: stimulates release of TSH from thyroid gland Antidiuretic hormone (ADH): promotes reabsorption of H 2 O by kidneys Oxytocin: induces labor and milk release from mammary glands in females Steroids Polypeptides Amino acid derivatives

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

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

Figure Parathyroid glands Pancreas (islets of Langerhans) Ovaries (in females) Insulin: decreases blood glucose Glucagon: increases blood glucose Estradiol: regulates development and maintenance of secondary sex characteristics in females; other effects Progesterone: prepares uterus for pregnancy Parathyroid hormone (PTH): increases blood Ca 2+ Steroids Polypeptides Amino acid derivatives

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 T4T3

Thyroid Gland

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

Figure 47-8 T3T3 Juvenile frog (tadpole) T3T3 Locomotion Respiration Excretion Nutrition Swim via movements of muscular tail Gas exchange occurs in gills, across skin, and in lungs Most are herbivorous; have a long gut specialized for digesting algae and plants Most nitrogenous wastes excreted as ammonia Adult frog Locomotion Respiration Nutrition Excretion Gas exchange occurs across skin, and in lungs Tailless; walk or hop Most nitrogenous wastes excreted as urea Most are carnivorous; have a large mouth or long tongue for catching prey; short gut specialized for digesting proteins

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 T 3 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.

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 T 3 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

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

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

Kitano, J. et al Adaptive divergence in the thyroid signaling pathway in the stickleback radiation. Current Biology 20: MarineStream

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

Experiment: For both marine and stream fish 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? Does T4 really affect metabolism?

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

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

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

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

Altering individual behaviors by altering overall thyroid levels seems like a pretty blunt way to go about changing specific phenotypes. How could this system be fine-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.