1. The Endocrine System Dr. Khalid Alregaiey

2. Learning Objectives List the general chemical categories of hormones and give examples of hormones within each category. Explain how different hormones can exert synergistic, permissive, or antagonistic effects. Explain how hormone concentrations in the blood are regulated Describe the mechanisms of actions of hormones

3. Endocrine System: Overview Endocrine system – the body’s second great controlling system which influences metabolic activities of cells by means of hormones Endocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymus The pancreas and gonads produce both hormones and exocrine products

4. Endocrine System: Overview The hypothalamus has both neural functions and releases hormones Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart

5. THE NERVOUS SYSTEM exerts point-to- point control through nerves, similar to sending messages by conventional telephone. Nervous control is electrical in nature and fast. THE ENDOCRINE SYSTEM broadcasts its hormonal messages to essentially all cells by secretion into blood and extracellular fluid. Like a radio broadcast, it requires a receiver to get the message - in the case of endocrine messages, cells must bear a receptor for the hormone being broadcast in order to respond. Endocrine System: Overview

6. Major Endocrine Organs

7. The Endocrine System

8. Autocrines and Paracrines Autocrines – chemicals that exert their effects on the same cells that secrete them Paracrines – locally acting chemicals that affect cells other than those that secrete them These are not considered hormones since hormones are long-distance chemical signals

9. Hormones Hormones – chemical substances secreted by cells into the extracellular fluids Regulate the metabolic function of other cells Have lag times ranging from seconds to hours Tend to have prolonged effects Are classified as amino acid-based hormones, or steroids

10. Types of Hormones Amino acid based – most hormones belong to this class, including: Amines (Tyrosine: Caecholamines and Thyroid hormones, Tryptophan: Melatonin) Polypeptide hormones protein hormones Steroids – Derived from Cholesterol, gonadal and adrenocortical hormones Fatty acid derived: Eicosanoids, derived from arachidonic leukotrienes and prostaglandins

11. A Structural Classification of Hormones

12. Hormone Action Hormones alter target cell activity by one of two mechanisms Cell membrane receptors: G Protein-coupled receptors Tyrosine kinase receptors Cytokines Receptors Cytoplasmic or nuclear receptors: Direct gene activation involving steroid hormones The precise response depends on the type of the target cell

13. Mechanism of Hormone Action Hormones produce one or more of the following cellular changes in target cells Alter plasma membrane permeability Stimulate protein synthesis Activate or deactivate enzyme systems Induce secretory activity Stimulate mitosis

14. Amino Acid-Based Hormone Action: cAMP Second Messenger Hormone (first messenger) binds to its receptor, which then binds to a G protein The G protein is then activated as it binds GTP, displacing GDP Activated G protein activates the effector enzyme adenylate cyclase Adenylate cyclase generates cAMP (second messenger) from ATP cAMP activates protein kinases, which then cause cellular effects

15. Amino Acid-Based Hormone Action: cAMP Second Messenger

16. Hormone binds to the receptor and activates G protein G protein binds and activates a phospholipase enzyme Phospholipase splits the phospholipid PIP 2 into diacylglycerol (DAG) and IP 3 (both act as second messengers) DAG activates protein kinases; IP 3 triggers release of Ca 2+ stores Ca 2+ (third messenger) alters cellular responses Amino Acid-Based Hormone Action: PIP-Calcium

18. Tyrosine Kinase Receptors (RTK)

19. Steroid hormones and thyroid hormone diffuse easily into their target cells Once inside, they bind and activate a specific intracellular receptor The hormone-receptor complex travels to the nucleus and binds a DNA-associated receptor protein This interaction prompts DNA transcription to produce mRNA The mRNA is translated into proteins, which bring about a cellular effect Steroid and Thyroid Hormones

21. Hormones circulate to all tissues but only activate cells referred to as target cells Target cells must have specific receptors to which the hormone binds These receptors may be intracellular or located on the plasma membrane Target Cell Specificity

22. Examples of hormone activity ACTH receptors are only found on certain cells of the adrenal cortex Thyroxin receptors are found on nearly all cells of the body Target Cell Specificity

23. Target cell activation depends on three factors Blood levels of the hormone Relative number of receptors on the target cell The affinity of those receptors for the hormone Up-regulation – target cells form more receptors in response to the hormone Down-regulation – target cells lose receptors in response to the hormone Target Cell Activation

24. Hormones circulate in the blood in two forms – free or bound Steroids and thyroid hormone are attached to plasma proteins Others are unbound Hormone Concentrations in the Blood

25. Concentrations of circulating hormone reflect: Rate of release Speed of inactivation and removal from the body Hormones are removed from the blood by: Degrading enzymes The kidneys Liver enzyme systems Hormone Concentrations in the Blood

26. Three types of hormone interaction Permissiveness – one hormone cannot exert its effects without another hormone being present Synergism – more than one hormone produces the same effects on a target cell Antagonism – one or more hormones opposes the action of another hormone Interaction of Hormones at Target Cells

27. Blood levels of hormones: Are controlled by negative and positive feedback systems Vary only within a narrow desirable range Hormones are synthesized and released in response to humoral, neural, and hormonal stimuli Control of Hormone Release

28. Feedback control Negative feedback is most common: for example, LH from pituitary stimulates the testis to produce testosterone which in turn feeds back and inhibits LH secretion Positive feedback is less common: examples include LH stimulation of estrogen which stimulates LH surge at ovulation

29. Negative feedback

30. Humoral Stimuli Humoral stimuli – secretion of hormones in direct response to changing blood levels of ions and nutrients Example: concentration of calcium ions in the blood Declining blood Ca 2+ concentration stimulates the parathyroid glands to secrete PTH (parathyroid hormone) PTH causes Ca 2+ concentrations to rise and the stimulus is removed

31. Humoral Stimuli

32. Neural Stimuli Neural stimuli – nerve fibers stimulate hormone release Preganglionic sympathetic nervous system (SNS) fibers stimulate the adrenal medulla to secrete catecholamines

33. Hormonal stimuli – release of hormones in response to hormones produced by other endocrine organs The hypothalamic hormones stimulate the anterior pituitary In turn, pituitary hormones stimulate targets to secrete still more hormones Hormonal Stimuli

35. Pituitary gland – two-lobed organ that secretes nine major hormones Neurohypophysis – posterior lobe (neural tissue) and the infundibulum Receives, stores, and releases hormones from the hypothalamus Adenohypophysis – anterior lobe, made up of glandular tissue Synthesizes and secretes a number of hormones Major Endocrine Organs: Pituitary (Hypophysis)

37. The posterior lobe is a downgrowth of hypothalamic neural tissue Has a neural connection with the hypothalamus (hypothalamic-hypophyseal tract) Nuclei of the hypothalamus synthesize oxytocin and antidiuretic hormone (ADH) These hormones are transported to the posterior pituitary Pituitary-Hypothalamic Relationships: Posterior Lobe

38. The anterior lobe of the pituitary is an outpocketing of the oral mucosa There is no direct neural contact with the hypothalamus Pituitary-Hypothalamic Relationships: Anterior Lobe

39. Major Endocrine Organs: Pituitary (Hypophysis)

40. Pituitary-Hypothalamic Relationships: Anterior Lobe

41. The six hormones of the adenohypophysis: Are abbreviated as GH, TSH, ACTH, FSH, LH, and PRL Regulate the activity of other endocrine glands In addition, pro-opiomelanocortin (POMC): Has been isolated from the pituitary Is enzymatically split into ACTH, opiates, and MSH Adenophypophyseal Hormones

42. The hypothalamus sends a chemical stimulus to the anterior pituitary Releasing hormones stimulate the synthesis and release of hormones Inhibiting hormones shut off the synthesis and release of hormones Activity of the Adenophypophysis

43. Hormones of the hypothalamus 1. Thyrotropin-releasing hormone (TRH), which causes release of thyroid-stimulating hormone 2. Corticotropin-releasing hormone (CRH), which causes release of adrenocorticotropin 3. Growth hormone–releasing hormone (GHRH), which causes release of growth hormone, and growth hormone inhibitory hormone (GHIH), alsocalled somatostatin, which inhibits release of growth hormone 4. Gonadotropin-releasing hormone (GnRH), which causes release of the two gonadotropic hormones, luteinizing hormone and follicle-stimulating hormone 5. Prolactin inhibitory hormone (PIH), which causes inhibition of prolactin secretion

44. The tropic hormones that are released are: Thyroid-stimulating hormone (TSH) Adrenocorticotropic hormone (ACTH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Activity of the Adenophypophysis

45. Gonadotropins – follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Regulate the function of the ovaries and testes FSH stimulates gamete (egg or sperm) production Absent from the blood in prepubertal boys and girls Triggered by the hypothalamic gonadotropin- releasing hormone (GnRH) during and after puberty Gonadotropins

46. In females LH works with FSH to cause maturation of the ovarian follicle LH works alone to trigger ovulation (expulsion of the egg from the follicle) LH promotes synthesis and release of estrogens and progesterone Functions of Gonadotropins

47. In males LH stimulates interstitial cells of the testes to produce testosterone LH is also referred to as interstitial cell- stimulating hormone (ICSH) Functions of Gonadotropins

48. Produced by somatotropic cells of the anterior lobe that: Stimulate most cells, but target bone and skeletal muscle Promote protein synthesis and encourage the use of fats for fuel Most effects are mediated indirectly by somatomedins Growth Hormone (GH)

49. Antagonistic hypothalamic hormones regulate GH Growth hormone–releasing hormone (GHRH) stimulates GH release Growth hormone–inhibiting hormone (GHIH) inhibits GH release Growth Hormone (GH)

51. GH stimulates liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factors Direct action promotes lipolysis and inhibits glucose uptake Metabolic Action of Growth Hormone

53. Tropic hormone that stimulates the normal development and secretory activity of the thyroid gland Triggered by hypothalamic peptide thyrotropin- releasing hormone (TRH) Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the release of TSH Thyroid Stimulating Hormone (Thyrotropin)

54. Stimulates the adrenal cortex to release corticosteroids Triggered by hypothalamic corticotropin- releasing hormone (CRH) in a daily rhythm Internal and external factors such as fever, hypoglycemia, and stressors can trigger the release of CRH Adrenocorticotropic Hormone (Corticotropin)

55. In females, stimulates milk production by the breasts Triggered by the hypothalamic prolactin-releasing hormone (PRH) Inhibited by prolactin-inhibiting hormone (PIH) Blood levels rise toward the end of pregnancy Suckling stimulates PRH release and encourages continued milk production Prolactin (PRL)

56. Physiology of posterior Pituitary gland Posterior pituitary hormones ADH also known as Vasopressin Oxytocin These hormones are synthesized in the neuron cell bodies in the hypothalamus and packed in secretory vesicles with neurophysin (carrier protein)

57. Posterior Pituitary Gland Does not synthesize hormones Consists of axon terminals of hypothalamic neurons Posterior pituitary gland

58. (vasopressin) Antidiuretic Hormone (ADH)

59. Synthesis of ADH It is synthesized as pre-prohormone and processed into a nonapeptide ADH synthesized in the cell bodies of hypothalamic neurons(supraoptic nucleus) ADH is stored in the posterior pituitary

60. Receptors of ADH (vasopressin) There are 2 types of receptors for ADH: V 1 V 2  V 1 receptors mediate vasoconstriction  V 2 receptors are located in the principle cells in distal convoluted tubule and collecting ducts in the kidneys

61. Mechanism of action of ADH: Antidiuresis ADH binds to V2 receptors on the principle cells of the distal convoluted tubules and collecting ducts. Via adenylate cyclase/cAMP induces production of specific proteins into the luminal membrane and enhances permeability of cell to water. Increased membrane permeability to water permits back diffusion of free water, resulting in increased urine osmolality (concentrates urine).

62. Mechanism of action of ADH

63. Control of ADH Release Osmotic pressure: Osmoreceptors in the hypothalamus  osmotic pressure   ADH secretion  osmotic pressure   ADH secretion Blood volume : Baroreceptor in carotid artery and aortic arch, and Stretch receptors in left atrium  blood pressure   ADH secretion  blood pressure   ADH secretion

64. Function of ADH (vasopressin)

65. ADH Increased Blood Pressure V1 receptor

66. Oxytocin

67. Synthesis of Oxytocin Oxytocin is synthesized in the cell bodies of hypothalamic neurons(paraventricular nucleus) Oxytocin is stored in the posterior pituitary

68. Functions of oxytocin  Suckling during breast-feeding o Contracts the myoepithelial cells of the alveoli  Childbirth (Parturition) o In late pregnancy, uterine smooth muscle (myometrium) becomes sensitive to oxytocin (positive feedback)

69. Summary of posterior pituitary hormones actions