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

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

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. 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

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 1.Regulating organic metabolism and H 2 O and electrolyte balance 2.Inducing adaptive changes to help the body cope with stressful situations 3.Promoting smooth, sequential growth and development 4.Controlling reproduction 5.Regulating red blood cell production 6.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 1.A single endocrine gland may produce multiple hormones n(Anterior Pituitary). 2.A single hormone may be secreted by more than one endocrine gland. For example, both the hypothalamus and pancreas secrete the hormone somatostatin. 3.Frequently, a single hormone has more than one type of target cells (Vasopressin) 4.The rate of secretion of some hormones varies considerably over the course of time in a cyclic pattern. 5.A single target cell may be influenced by more than one hormone.

25. Cont.. 6.The same chemical messenger may be either a hormone or a neurotransmitter 7.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:  Adenylate cyclase which catalyzes the conversion of ATP to cyclic AMP;  Guanylate cyclase 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 and diacyl glycerol.

29. Adenyl Cyclase–cAMP Second Messenger System Hormone binds to the receptor GDP is released from G protein Activate adenyl cyclase which convert ATP to cAMP cAMP activates tyrosine kinase A Tyrosine kinase A phosphorylate specific protein for physiological action

30. IP 3 Mechanism Hormone binds to the receptor Phospholipase C liberates DAG & IP 3 IP 3 mobilizes Ca ++ from ER Ca ++ and DAG activates tyrosine kinase C Tyrosine kinase C phosphorylate specific protein for physiological action

31. Calcium-Calmodulin Second Messenger 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 PropertiesPeptidesCatechol-aminesThyroid Hormone Steroids Synthesis and storage Polyribosomes -ER as preprohormones/ Vesicles Cytosol/ ATP Ca++ / Chromagranin Vesicles Colloid of follicular cells pendrin (iodide/chloridetransp orter Mitochondria/ cytosol Release from parent cell Exocytosis thyroglobulin to megalin endocytosis/ lysosomal degradation diffusion Transport in blood Most are freeLoosely bound to albumin TBG, transthyretin, albumin Albumin sex hormone or sex hormone or corticosteroid BG Half life Minutes1-2 MinutesT4- 7days, T3- 18 dayshours Location of receptor plasma membrane intracellular Response to receptor-ligand binding protein phosphorylation genomic genomic

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