1. ENDOCRINE SYSTEM OVERVIEW

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 work to maintain homeostasis (internal environment 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. 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.

7. 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.

8. RECEPTORS  A target cell responds to a hormone because it bears receptors for the hormone.  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?

9. Human Endocrine System (major glands)

10. Hormones  Chemical substances released from endocrine glands or specialized cells (e.g., neuroendocrine cells) directly into blood to produce a systemic physiological response.  They slow down or speed up the biological functions according to body needs (they do not initiate activities).

11. 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 hormones.

12. 1- Endocrine hormones: circulate in blood throughout body. 2- Local hormones: Paracrines: tissue hormones act on nearby cells only, include cytokines, neurotrophins, and prostaglandins. Autocrines: act on the same cells that secrete them. Types of Hormones

13. 1)Protein hormones: more than 100 amino acids (Growth Hormone & Prolactin). 2)Polypeptides: less than 100 amino acids (insulin). 3)Glycoprotein: > 100 amino acids with carbohydrate (FSH & LH). 4)Amino acid derivatives: derived from tyrosine (epinephrine, norepinephrine & thyroxine) 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.  Calcitriol (1, 25 dihydroxy cholecalciferol). Types of Hormones

14. MECHANISM OF HORMONAL ACTION Response depends on both hormone and target cells. 1)Lipophilic (Lipid-soluble) hormones: pass through the plasma membrane of target cells and bind to intracellular receptors, thereby regulating target cell genes. 1)Hydrophilic (Water-soluble) hormones: cannot pass through plasma membranes, and thus use second messengers within the target cells, such as cyclic AMP, IP 3, and Ca ++, for mediation.

16. 1- Hormones That Do Not Enter Cells Hormones that are too large or too polar to cross plasma membranes include all peptides, 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.

17. The polar hormones bind to receptors located on the outer surface of the cell membrane. This activates enzymes that enlist second-messenger molecules.  Many hormones activate adenylate cyclase when they bind to their receptors. This enzyme produces cyclic AMP (cAMP), which activates protein kinase enzymes within the cell cytoplasm.  Other hormones may activate phospholipase C when they bind to their receptors. This leads to the release of inositol triphosphate (IP 3 ), which stimulates the endoplasmic reticulum to release Ca 2+ into the cytoplasm, activating calmodulin.  The membrane receptors for insulin and various growth factors are tyrosine kinase enzymes that are activated by binding to the hormone. Once activated, the receptor kinase phosphorylates signaling molecules in the cytoplasm that can have many effects. Second messengers

18.  Second messengers include: 1)cyclic AMP 2)cyclic GMP (e.g. Atrial natriuretic peptide) 3)Intracellular Ca 2+ 4)phospholipase C which catalyzes phosphoinositide turnover producing inositol triphosphates (IP 3 ) & diacyl glycerol (DAG).

19. 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)

21. 2- Hormones That Enter Cells Lipophilic hormones  Lipophilic hormones (steroids and thyroid hormones) bind to intracellular receptors, which function as ligand-dependant transcription factors.  Some steroid hormones bind to cytoplasmic receptors, which then move into the nucleus. Other steroids and thyroxine bind to receptors already in the nucleus.  Each receptor binds to both the hormone and to a region of DNA called a hormone-response element.

22. Steroids action

23. 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

24. Table 18-3, p. 674

25. 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.

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

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