2. Hormones in Animals Endocrinology D R Davies School of Biological Sciences Purves Life: the Science of Biology Chapters 41 (Animal Hormones) and 15 (Cell Signalling)

3. Lecture 13 Learning Outcomes At the end of this lecture you should be able to: Describe the general properties of hormones, with examples Know the location of the major endocrine glands and the types of hormone secreted Outline the steps in the study of hormones Explain the different types of hormone receptor and describe in outline the transduction mechanism

4. Communication between cells in multicellular organisms For a multicellular organism to survive it must be able to respond to changes in the external and internal environment - individual cells must be able to communicate with one another communication between cells occurs via 4 distinct mechanisms  Cell-to-cell communication via gap junctions in the plasma membrane  Paracrine control via locally acting chemical signals  Electrical signals via the nervous system  By chemical signals (hormones) released into the bloodstream

5. Definition of hormone A specific chemical substance formed in one organ (endocrine gland) and transported in the bloodstream to another organ (Target Organ)where it affects the metabolism of that organ. First coined in 1902 by Bayliss and Starling who were the first to show the existence of the hormone - secretin.

6. Definition of hormone (2) Hormones are information transferring molecules which move from one cell to another for the benefit of the organism as a whole Huxley) Endocrine Cell Target Cell H

7. Physiological effects of hormones are proportional to hormone concentration Hormones are only effective over a narrow concentration range The EC 50 value is the hormone concentration required to produce 50% of the maximal response 100% 50%

8. Hormones: do not initiate reactions but rather they effect the rate of pre-existing metabolic functions in a positive or negative fashion some hormones have specific effects on a single cell type, others a more general effect hormones are effective at minute concentrations - range 10 -12 to 10 -8 M hormones have a very short half-life in circulation ( ranging from minutes to hours)

9. Hormone concentration Hormones are inactivated or degraded to an inactive form (H*)at a constant rate It follows that the level of hormone in circulation is dependent on the rate of secretion Endocrine Cell Target Cell [H] H*

10. Physiological effects of hormones are timed responses The effects of hormones occur in a regulated and timed manner Hormone levels increase in response to a physiological signal which results in an increased secretion of hormone hormone levels decrease when secretion ceases

12. Hypothalamus: releasing peptide hormone acting on the anterior pituitary : GHRH, CRH, TRH GnRH Anterior Pituitary: Growth Hormone (GH), Corticotrophin (ACTH), Thyroid Stimulating hormone (TSH), Luteinizing hormone (LH), Follicle stimulating hormone (FSH) Posterior Pituitary: oxytocin, vasopressin (ADH) Pancreatic Islets of Langerhans: insulin and glucagon Adrenal cortex: aldosterone and cortisol Adrenal Medulla: Adrenaline and Noradrenaline Thyroid Gland: thyroxine and Tri-iodothyronine Testis: testosterone (androgen) Ovary and placenta: oestradiol (oestrogens), progesterone

14. Different types of hormones Glycoprotein hormones e.g TSH, LH and FSH Small peptide hormones : oxytocin, vaspressin (ADH) GnRH Larger peptide hormones: insulin, ACTH Catecholamine hormones: adrenaline and noradrenaline (a.k.a. epinephrine and norepinephrine in the USA) Thyroid hormone: thyroxine and triiodothyronine Steroid hormones: cortisol, progesterone, testosterone, (o)estradiol Fatty Acid -based hormones: prostaglandins

16. Peptide Hormones from the Posterior Pitutary

17. Insulin Structure

19. Steroid Hormones Lipid hormones Cross plasma membranes readily Interact with intracellular receptors Regulate gene transcription

21. Adrenaline (epinephrine)

22. Methods of studying hormones and their effects Removal of the source of hormones: If you remove the endocrine gland there is a measurable physiological consequence: remove pancreas - causes diabetes mellitus (high blood glucose) destroy  -cells in pancreas by injecting streptozotocin - also results in diabetes castration - results in loss of secondary sexual characteristics

23. Methods of studying hormones and their effects Make extracts of the removed tissue and administer the the hormone deficient animal: there is a measurable reversal physiological consequence: pancreatic extracts lower blood glucose) in streptozotocin - induced in diabetes administration of testosterone restores secondary sexual characteristics Proof that the endocrine gland secretes a chemical agent with hormonal effects

24. Methods of studying hormones and their effects Identify and characterise the hormone Make a synthetic version of the hormone and show that it has similar effects Identify the target tissue (s) What are the metabolic and physiological effects of the hormone? Make radiolabelled hormone (e.g. I 125 -insulin, 3 H- oestradiol Hormone specfically retained in target tissue (by a high affinity receptor) Examine properties of hormone receptor Purify and characterise receptor characterise the metabolic effects of hormone within the target tissue

25. Hormones which bind to plasma membrane receptors: Hormones bind to specific receptors on the outside of the plasma membrane of the cell and exert rapid and specific effects on metabolism and longer term effects gene transcription

26. G-protein linked receptors e.g. adrenaline and glucagon receptors Activated! Second Messenger Effects

27. Activation of Insulin Receptor

28. Effects of Hormones In all cases activation of the receptor can lead to a cascade of related and consequential molecular events inside the cell. Events including generation of second messengers, changes in ion fluxes, activation or inhibition of protein kinases, activation or inhibition of transcription factors eventually lead to the regulation of the activity of key metabolic enzymes or other cellular function or changes in the level of transcription of genes coding for key proteins

29. Intracellular Signalling Cascades Signal Transfer Signal Transformed and Relayed Signal Amplified Signal Diverges Modulated Effect

30. Signalling via the insulin receptor

31. Mode of Action of Steroid and Thyroid Hormones These hormones are produced continuously They are not stored in the endocrine gland The hormones cross cell membranes readily Bind to receptors in the cytoplasm or nuclei of target cells These steroid-receptor complexes act as transcription factors regulating specific gene expression The effects of steroid and thyroid hormones usually take several hours to take effect

33. Activation of Protein Kinases