The Endocrine System

1. The Endocrine System

2. Types of Chemical Messengers A hormone is a chemical that is secreted into extracellular fluid and carried by the blood -Can therefore act at a distance from source -Only targets with receptor can respond Paracrine regulators do not travel in blood -Allow cells of organ to regulate each other Pheromones are chemicals released into the environment to communicate among individuals of a single species

3. Endocrine System The endocrine system includes all the organs and tissues that produce hormones • Includes endocrine glands,which are specialized to secrete hormones • Also organs, like the liver, that secrete hormones in addition to other functions Exocrine glands secrete their products, such as saliva or milk, into a duct for transport to the outside

4. Feedback Mechanisms • For hormone secretion regulated by the negative feedback loop: when gland X releases hormone X, this stimulates target cells to release hormone Y. When there is an excess of hormone Y, gland X "senses" this and inhibits its release of hormone X.

5. Types of Chemical Messengers Some neurotransmitters are distributed by the blood and act asneurohormones -Norepinephrine coordinates the activity of heart, liver and blood vessels during stress Hormone production and release is often regulated directly or indirectly by the nervous system

6. Classes of Hormones Molecules that function as hormones must exhibit two basic characteristics 1. Must be sufficiently complex to convey regulatory information to their target cells 2. Must be adequately stable to resist destruction before reaching their target cells Three chemical classes meet these requirements

7. Classes of Hormones 1. Peptides and proteins -Glycoproteins 2. Amino acid derivatives -Catecholamines -Thyroid hormones -Melatonin 3. Steroids -Sex steroids -Corticosteroids

8. Classes of Hormones Hormones may be categorized as: -Lipophilic (nonpolar) = fat-soluble -Steroid hormones and thyroid hormones -Bind to intracellular receptors -Hydrophilic (polar) = water-soluble -All other hormones -Bind to extracellular receptors

10. Testosterone Cortisol (Hydrocortisone) Thyroxine CH2OH OH C O H3C I I H3C COOH OH HO H3C CH2 CH HO O H3C NH2 I I O O Lipophilic Hormones Lipophilic hormones include the steroid hormones (derived from cholesterol) and the thyroid hormones (tyrosine + iodine) -As well as the retinoids, or vitamin A

11. Lipophilic Hormones These hormones circulate in the blood bound to transport proteins -Dissociate from carrier at target cells -Pass through the cell membrane and bind to an intracellular receptor, either in the cytoplasm or the nucleus -Hormone-receptor complex binds to hormone response elements in DNA-Regulate gene expression

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1. Hormone passes through plasma membrane Blood plasma Lipophilic hormones Plasma membrane Cytoplasm Nucleus 2. Inside target cell the hormone binds to a receptor protein in the cytoplasm or nucleus Receptor 3. Hormone-receptor complex binds to hormone response element on DNA, regulating gene transcription 5. Change in protein synthesis is cellular response mRNA Protein DNA 4. Protein synthesis Hormone response element

13. Hydrophilic Hormones Hydrophilic hormones include the peptide, protein and catecholamine hormones -Too large or polar to cross cell membrane Hormones bind to extracellular receptors -Initiate signal transduction pathways 1. Activation of protein kinases 2. Production of second messengers

14. Hydrophilic Hormones Receptor kinases • For some peptide hormones (like insulin) the receptor itself is a kinase • Can directly phosphorylate intracellular proteins that alter cellular activity • For other peptide hormones (like growth hormone) the receptor itself is not a kinase • Rather, it activates intracellular kinases

15. Hydrophilic Hormones Second-messenger systems • Many hydrophilic hormones work through second messenger systems • Two have been described: • One involving cyclic adenosine monophosphate (cAMP) • One that generates 2 lipid messengers: inositoltriphosphate (IP3) and diacyl glycerol (DAG)

16. Hydrophilic Hormones Second-messenger systems • Receptors are linked to a second-messenger-generating enzyme via membrane proteins called G proteins • Are thus called G-protein-coupled receptors (GPCP) • When the G protein activates the enzyme, the second-messenger molecules increase

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1. Receptors Function as Kinase Enzymes 2. Receptors Activate G Proteins Hormones Second messenger- generating enzyme Hormone GPCR GPCR Receptor g b a GTP GTP GDP Active G protein Second messenger Inactive G protein Inactive Active kinase domain Active Protein kinase ADP ATP Inactive protein kinase P P P P Target proteins Target protein Phosphorylated protein Cellular response Cellular response

18. Paracrine Regulators Paracrine regulation occurs in most organs • Growth factors are proteins that promote growth and cell division in specific organs • Epidermal growth factor = Skin • Nerve growth factor = Neurons • Insulin-like growth factor = Bone • Cytokines = Immune system

19. Paracrine Regulators Prostaglandins • A diverse group of fatty acids that are produced in almost every organ • Regulate a variety of functions including: • Smooth muscle contraction, lung function, labor, and inflammation • Synthesis is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen

20. Paracrine Regulators The endothelium of blood vessels is a rich source of paracrine regulators • Nitric oxide (NO) which promotes vasodilation • Endothelinwhich stimulates vasoconstriction • Bradykininwhich promotes vasodilation

21. The Pituitary Gland The pituitary gland is also known asthehypophysis • It hangs by a stalk from the hypothalamus The pituitary gland consists of two parts: • Anterior pituitary (adenohypophysis) • Appears glandular • Posterior pituitary (neurohypophysis) • Appears fibrous

22. Anterior Pituitary Disorders Growth hormone stimulates growth of muscles and connective tissue • It also promotes the production of insulin-like growth factors • Stimulate cell division in the epiphyseal growth plates, and thus bone elongation Gigantism is caused by an excessive secretion of growth hormone in a child In contrast, pituitary dwarfism is caused by a deficiency in GH secretion during childhood

23. Feedback mechanisms in the control of blood osmotic pressure—the control of ADH.

24. The Thyroid Gland In humans, the thyroid gland is shaped like a bow tie, and lies just below the Adam’s apple in the front of the neck • It secretes: • Thyroid hormones • Thyroxine • Triiodothyronine • Calcitonin

25. The Thyroid Gland Thyroidhormones bind to nuclear receptors -Regulate carbohydrate & lipid metabolism -Adults with hypothyroidism have low production of thyroxine -Reduced metabolism and overweight -Adults with hyperthyroidism have high production of thyroxine -High metabolism and weight loss -Trigger metamorphosis in amphibians

26. The Parathyroid Glands The parathyroid glands are four small glands attached to the thyroid • Produce parathyroid hormone (PTH) in response to falling levels of Ca2+ in blood • Stimulates osteoclasts to dissolve calcium phosphate crystals in the bone matrix and release Ca2+ into blood • Stimulates the kidneys to reabsorb Ca2+ from the urine

27. The Adrenal Glands The adrenal glands are located just above each kidney • Medulla = Inner portion • Stimulated by the sympathetic division of the autonomous nervous system • Cortex = Outer portion • stimulated by the anterior pituitary, through the hormone ACTH

28. The Pancreas Insulin -Secreted by beta (b) cells of the islets -Stimulates cellular uptake of blood glucose and its storage as glycogen in the liver and muscle cells or as fat in fat cells Glucagon -Secreted by alpha (a) cells of the islets -Promotes the hydrolysis of glycogen in the liver and fat in adipose tissue