1. ENDOCRINE SYSTEM OVERVIEW Dr. Hany Ahmed Assistant Professor of Physiology (MD, PhD). Al Maarefa Colleges (KSA) & Zagazig University (ARE) Specialist of Diabetes, Metabolism and Obesity Zagazig Obesity Management & Research Unit Dr. Hany Ahmed Assistant Professor of Physiology (MD, PhD). Al Maarefa Colleges (KSA) & Zagazig University (ARE) Specialist of Diabetes, Metabolism and Obesity Zagazig Obesity Management & Research Unit

2. Objectives Understanding the common aspects of neural and endocrinal regulations. Describing the chemical nature of hormones. Describing the types of hormones. Understanding the different mechanisms of hormonal action & concept of second messenger system. Understanding the common aspects of neural and endocrinal regulations. Describing the chemical nature of hormones. Describing the types of hormones. Understanding the different mechanisms of hormonal action & concept of second messenger system.

3. Introduction Body systems always work to maintain homeostasis (internal milieu of the body as blood pressure, pH, water and electrolyte balance, temperature, etc.) Major regulatory systems of body: 1- Nervous system 2- Endocrine system Nervous and Endocrine systems act together to coordinate functions of all body systems. These systems communicate by way of electrical and/or chemical signals

4. Regulatory Systems  Act together to coordinate functions of all body systems. 1- Nervous system:  Nerve impulses / Neurotransmitters.  Faster responses, briefer effects, acts on specific targets. 2- Endocrine system:  Its information is conveyed via hormones released directly into blood and diffuse to the tissues to regulate their functions.  Slower responses, effects last longer, broader influence.

5. Fig. 13.2

6. Endocrine gland Axon Paracrine regulator Receptor proteins Target cell Neurotransmitter Hormone carried by blood

7. Role of endocrine system 1)Regulating the body functions. Along with autonomic nervous system, controlling activities of both circulatory and digestive systems. 2)Controlling cellular metabolism as growth & secretion. 3)Controlling the rate of chemical reactions in cells. 4)Controlling transport of substances through cell membrane. 5)Controlling Reproduction. 6)Regulating Red blood cells production.

8. Features of Endocrinology The endocrine system consists of the ductless endocrine glands that are scattered throughout the body. Its information is conveyed via hormones released directly into blood and diffuse to tissues to regulate their functions. Its speed of response is relatively slow (some hormonal effects occur within seconds while others require days to start). It is largely a self-regulating system.

9. A cell is a target as it has a specific receptor for the hormone  Most hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells.  A target cell responds to a hormone because it bears receptors for the hormone.

10. 10 What is a “receptor”? It is a protein made by the target cell (protein synthesis after gene expression). The protein is made, then inserted into plasma membrane, or found in cytoplasm or nucleus. The active site on the protein “fits” the hormone. Acts to convert the signal into a response. What would happen if there was a gene defect in the DNA code for a receptor? What would happen if the receptor protein was denatured?

11. Human Endocrine System (major glands)

12. Hormones  Chemical substances released from endocrine glands or specialized cells (e.g., neuroendocrine cells) directly into blood to produce a systemic physiological response.  Their target organ is either a subordinate endocrine gland (glandotropic hormone) or non- endocrine tissue (aglandotropic hormone).  They slow down or speed up the biological functions according to body needs (they do not initiate activities).

13. Types of Hormones According to the distance the hormone travels: – Endocrine – Paracrine – Autocrine According to solubility: – Hydrophilic e.g. Peptide hormones. – Lipophilic e.g. Steroid & thyroxine.

14. 1- Endocrine hormones: circulate in blood throughout the body. 2- Local hormones: Paracrines: tissue hormones act on nearby cells only. Autocrines: act on the same cells that secrete them. Types of Hormones

15. 1)Protein hormones: more than 100 amino acids (Growth Hormone & Prolactin). 2)Polypeptides: less than 100 amino acids (insulin). 3)Glycoprotein: more than 100 amino acids with carbohydrate (FSH & LH). 4)Amines: derived from tyrosine amino acid (epinephrine & norepinephrine) or from tryptophan (melatonin). 5)Steroids: derived from cholesterol as:  Sex steroids: testosterone, estradiol, progesterone are secreted by testes, ovaries, placenta and adrenal cortex.  Corticosteroids: cortisol and aldosterone are secreted by adrenal cortex. Types of Hormones

16. Types of Hormone

17. MECHANISM OF HORMONAL ACTION Response depends on both hormone and target cells. 1)Lipophilic (Lipid-soluble) hormones bind to receptors inside target cells. 2)Hydrophilic (Water-soluble) hormones bind to receptors on the plasma membrane – Activates second messenger system. – Amplification of original small signal.

19. 1- Hormones That Do Not Enter Cells Hormones that are too large or too polar to cross plasma membranes include all peptide, glycoprotein hormones, as well as catecholamines. They bind to receptors located on the outer surface of the plasma membrane triggering reactions inside cells through second messenger mechanisms. Many of these hormones induce the release of intracellular second messengers that transmit the hormone signal inside the cell.

20. Second messengers for cell-surface receptors  Second messengers include: 1)cyclic AMP 2)cyclic GMP 3)Ca 2+ 4)phospholipase C which catalyzes phosphoinositide turnover producing inositol triphosphates (IP 3 ) & diacyl glycerol (DAG). 5)Nitric oxide (NO)

21. Cell mechanism & Second messengers G Protein–Linked Hormone Receptors: Many hormones activate receptors that indirectly regulate the activity of target proteins (e.g., enzymes or ion channels) by coupling with groups of cell membrane proteins called heterotrimeric GTP-binding proteins (G proteins)

23. 2- Hormones That Enter Cells Lipophilic hormones

24. 1 Lipid-soluble hormone diffuses into cell Blood capillary Target cell Transport protein Free hormone 1 Lipid-soluble hormone diffuses into cell Blood capillary Activated receptor-hormone complex alters gene expression Nucleus Receptor mRNA DNA Cytosol Target cell Transport protein Free hormone 2 1 Lipid-soluble hormone diffuses into cell Blood capillary Activated receptor-hormone complex alters gene expression Nucleus Receptor mRNA Newly formed mRNA directs synthesis of specific proteins on ribosomes DNA Cytosol Target cell Transport protein Free hormone Ribosome 2 3 1 Lipid-soluble hormone diffuses into cell Blood capillary Activated receptor-hormone complex alters gene expression Nucleus Receptor mRNA Newly formed mRNA directs synthesis of specific proteins on ribosomes DNA Cytosol Target cell New proteins alter cell's activity Transport protein Free hormone Ribosome New protein 2 3 4

25. Table 18-3, p. 674

26. Down regulation of receptors This process is illustrated by the insulin receptor sites on target cells in a person with type 2 diabetes. Due to the elevated levels of blood glucose in an overweight individual, β-cells of Langerhans in pancreas must release more insulin than normal to meet the demand and return the blood to homeostatic levels. The near-constant increase in blood insulin levels results from an effort to match the increase in blood glucose, which will cause receptor sites on the liver cells to down regulate and decrease the number of receptors for insulin, increasing the subject’s resistance by decreasing sensitivity to this hormone. This is the more common process of insulin resistance, which leads to adult-onset diabetes.

27. Up Regulation of receptors An increase in the number of receptors on the surface of target cells, making the cells more sensitive to a hormone or another agent. For example, there is an increase in uterine oxytocin receptors in the third trimester of pregnancy, promoting the contraction of the smooth muscle of the uterus.

28. Feedback control The effective plasma conc. of a hormone is regulated by Feedback control: -ve feedback mech.:  Anterior pituitary hormones  stimulate target gland. (  TSH from Anterior pituitary   Thyroxine from thyroid gland).  E.g. ↓ Thyroxine  ↑ TSH release from Anterior pituitary ↑ Thyroxine  ↓ TSH.

29. Endocrine disorders Result mainly from 1.Hormone excess (hypersecretion)or 2.Deficiency (hyposecretion)or 3.Decreased target-cell responsiveness

31. References  Human physiology, Lauralee Sherwood, seventh edition.  Text book physiology by Guyton & Hall,11 th edition.  Physiology by Berne and Levy, sixth edition. 31

32. " والله في عون العبد مادام العبد فى عون أخيه "