OVERVIEW ENDOCRINE SYSTEM

1. OVERVIEW ENDOCRINE SYSTEM ENDO BLOCK 412 Dr. ShaikhMujeeb Ahmed Assistant Professor AlMaarefa College

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

3. Objectives • Understanding the common aspects of neural and endocrinal regulations. • Describing the chemical nature of hormones • Recalling the overall hormonal functions • Understanding the different mechanisms of hormonal action & concept of second messenger system

4. Introduction • Body systems always works to maintain homeostasis • Two major regulatory systems of body are • Nervous system • Endocrine system

6. Nervous and Endocrine Systems • Act together to coordinate functions of all body systems • Nervous system • Nerve impulses/ Neurotransmitters • Faster responses, briefer effects, acts on specific target • Endocrine system • Hormone – mediator molecule released in 1 part of the body but regulates activity of cells in other parts • Slower responses, effects last longer, broader influence

7. Fig. 13.2

8. Comparison between Nervous and Endocrine system

9. Nervous system • The nervous system exerts point-to-point control through nerves, similar to sending messages by intercom. Nervous control is electrical in nature and fast.

10. Hormones travel via the bloodstream to target cells • 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.

11. General Principles of Endocrinology • The endocrine system consists of the ductless endocrine glands that are scattered throughout the body. • The endocrine glands are not connected anatomically • They constitute a system in a functional sense. • Secreting hormones into the blood • Once secreted, a hormone travels in the blood to its distant target cells, where it regulates or directs a particular function. • Endocrinology is the study of the homeostatic chemical adjustments and other activities that hormones accomplish.

12. A cell is a target because is 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.

13. Hormone receptors

14. Types of Hormone • According to the distance the hormone travel • Endocrine • Paracrine • Autocrine • Intracrine • According to solubility • Hydrophilic eg. Peptide, hormone • Lipophilic eg. Steroid & thyroid hormone

15. Types of Hormone

16. Hormone types • Circulating – circulate in blood throughout body • Local hormones – act locally • Paracrine – act on neighboring cells • Autocrine – act on the same cell that secreted them

17. Characteristics of Peptide hormone • Produced and processed by the endoplasmic reticulum and Golgi complex of the endocrine cell • Stored in secretory vesicles until signaled for release by exocytosis. • Circulate in the blood largely dissolved in the plasma • Bind with surface membrane receptors of their target cells, • Act primarily through second-messenger pathways to alter the activity of preexisting proteins, such as enzymes, to produce their physiologic response. • The peptide molecule prepared first is usually a larger precursor called as Preprohormone;It is cleaved to form Prohormone;further cleavage of Prohormone, forms the final mature Hormone. Example: Preproinsulin→Proinsulin →Insulin This hormone is stored in vesicles of endocrine cells and released on demand

18. Blood capillary Blood capillary Blood capillary Blood capillary Blood capillary Blood capillary 1 1 1 1 1 1 Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Water-soluble hormone Water-soluble hormone Water-soluble hormone Water-soluble hormone Water-soluble hormone Water-soluble hormone Adenylate cyclase Adenylate cyclase Adenylate cyclase Adenylate cyclase Adenylate cyclase Adenylate cyclase Receptor Receptor Receptor Receptor Receptor Receptor Second messenger Second messenger Second messenger Second messenger Second messenger G protein G protein G protein G protein G protein G protein 2 2 2 2 2 ATP ATP ATP ATP ATP Activated adenylate cyclase converts ATP to cAMP Activated adenylate cyclase converts ATP to cAMP Activated adenylate cyclase converts ATP to cAMP Activated adenylate cyclase converts ATP to cAMP Activated adenylate cyclase converts ATP to cAMP cAMP cAMP cAMP cAMP cAMP 6 Phosphodiesterase inactivates cAMP Protein kinases Protein kinases Protein kinases Protein kinases 3 3 3 3 cAMP serves as a second messenger to activate protein kinases cAMP serves as a second messenger to activate protein kinases cAMP serves as a second messenger to activate protein kinases cAMP serves as a second messenger to activate protein kinases Activated protein kinases Activated protein kinases Activated protein kinases Activated protein kinases 4 4 4 Activated protein kinases phosphorylate cellular proteins Activated protein kinases phosphorylate cellular proteins Activated protein kinases phosphorylate cellular proteins Protein Protein Protein ATP ATP ATP ADP ADP ADP Protein— Protein— Protein— P P P 5 5 Millions of phosphorylated proteins cause reactions that produce physiological responses Millions of phosphorylated proteins cause reactions that produce physiological responses Target cell Target cell Target cell Target cell Target cell Target cell

19. Characteristics of lipophilic Steroid hormone • By stepwise modifications of a basic cholesterol precursor molecule. • Steroidogenic(“steroid-producing”) organs specialize in the type of hormones they produce because each of these organs has the enzymes necessary to produce only one or several, not all, of the steroid hormones. • Steroid hormones act primarily by activating genes on binding with receptors inside the cell, thus bringing about formation of new proteins in the target cell that carry out the desired response. • lipophilic hormones are largely bound to plasma proteins.

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

21. Characteristics of lipophilic thyroid hormone • synthesized by a unique pathway within the thyroid gland but functions at its target cells by means similar to those used by lipophilic steroids.

22. OVERALL FUNCTIONS OF THE ENDOCRINE SYSTEM • Regulating organic metabolism and H2O and electrolyte balance • Inducing adaptive changes to help the body cope with stressful situations • Promoting smooth, sequential growth and development • Controlling reproduction • Regulating red blood cell production • Along with the autonomic nervous system, controlling and integrating activities of both the circulatory and digestive systems

23. TROPIC HORMONES • A hormone that has as its primary function the regulation of hormone secretion by another endocrine gland is classified functionally as a tropic hormone (tropic means “nourishing”). • Example: Thyroid stimulating hormone (TSH), Adrenocorticotropic hormone (ACTH) etc.

24. COMPLEXITY OF ENDOCRINE FUNCTION • A single endocrine gland may produce multiple hormones n(Anterior Pituitary). • A single hormone may be secreted by more than one endocrine gland. For example, both the hypothalamus and pancreas secrete the hormone somatostatin. • Frequently, a single hormone has more than one type of target cells (Vasopressin) • The rate of secretion of some hormones varies considerably over the course of time in a cyclic pattern. • A single target cell may be influenced by more than one hormone.

25. Cont.. • The same chemical messenger may be either a hormone or a neurotransmitter • Some organs are exclusively endocrine in function (they specialize in hormone secretion alone, the anterior pituitary being an example), whereas other organs of the endocrine system perform non endocrine functions in addition to secreting hormones (the testes).

26. Mechanisms of Hormone Action • Response depends on both hormone and target cell • Lipid-soluble hormones bind to receptors inside target cells • Water-soluble hormones bind to receptors on the plasma membrane • Activates second messenger system • Amplification of original small signal

27. 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)

28. Second messengers for cell-surface receptors • Second messenger systems include: • Adenylatecyclase which catalyzes the conversion of ATP to cyclic AMP; • Guanylatecyclase which catalyzes the conversion of GMP to cyclic GMP (cyclic AMP and cyclic GMP are known collectively as cyclic nucleotides); • Calcium and calmodulin; phospholipase C which catalyzes phosphoinositide turnover producing inositol phosphates anddiacyl glycerol.

29. AdenylCyclase–cAMP SecondMessenger System • Hormone binds to the receptor • GDP is released from G protein • Activate adenylcyclase which convert ATP to cAMP • cAMP activates tyrosine kinase A • Tyrosine kinase A phosphorylate specific protein for physiological action

30. IP3 Mechanism • Hormone binds to the receptor • Phospholipase C liberates DAG & IP3 • IP3 mobilizes Ca++ from ER • Ca++ and DAG activates tyrosine kinase C • Tyrosine kinase C phosphorylate specific protein for physiological action

31. Calcium-Calmodulin SecondMessenger System • Hormone binds to the receptor • Open Ca++ channels & release Ca++ from ER • Ca++ binds to calmodulin to produce physiological action

32. Table 18-3, p. 674

33. Sequence of Steroid hormone action

34. Summary of Chemical Structure, Synthesis, and Transport of Hormones

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