Chapter 18: The Endocrine System Copyright 2009, John Wiley & Sons, Inc.

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 a part of the body to regulates activity of cells in other parts Slower responses, effects last longer, broader influence Copyright 2009, John Wiley & Sons, Inc.

Nervous and Endocrine Systems Copyright 2009, John Wiley & Sons, Inc.

Copyright 2009, John Wiley & Sons, Inc. Body Glands 2 kinds of glands Exocrine – ducted Sweat, mucous, and digestive glands. Endocrine – ductless Secrete products into interstitial fluid, diffuse into blood Endocrine glands include Pituitary, thyroid, parathyroid, adrenal and pineal glands Organs not exclusively endocrine glands Hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, liver, small intestine, skin, heart, adipose tissue, and placenta. Copyright 2009, John Wiley & Sons, Inc.

Copyright 2009, John Wiley & Sons, Inc. Hormone Activity Hormones work through receptors Hormones affect only specific target tissues with specific receptors Receptors constantly synthesized and broken-down Copyright 2009, John Wiley & Sons, Inc.

Copyright 2009, John Wiley & Sons, Inc. Hormone Activity Hormones work through receptors Hormones affect only specific target tissues with specific receptors Receptors constantly synthesized and broken-down Down-regulation & Up-regulation Copyright 2009, John Wiley & Sons, Inc.

Copyright 2009, John Wiley & Sons, Inc. Hormone Activity Hormones work through receptors Hormones affect only specific target tissues with specific receptors Receptors constantly synthesized and broken-down They operate within feedback systems to maintain an optimal internal environment They are excreted by the kidney, deactivated by the liver or by other mechanisms Copyright 2009, John Wiley & Sons, Inc.

Copyright 2009, John Wiley & Sons, Inc. 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 Copyright 2009, John Wiley & Sons, Inc.

Chemical classes of hormones Lipid-soluble – use transport proteins Steroid Thyroid Nitric oxide (NO) Water-soluble – circulate in “free” form Amine Peptide/ protein Eicosanoid Copyright 2009, John Wiley & Sons, Inc.

Lipid-soluble Hormones Steroids lipids derived from cholesterol on SER different functional groups attached to core of structure provide uniqueness Thyroid hormones tyrosine ring plus attached iodines are lipid-soluble Nitric oxide is gas

Water-soluble Hormones Amine, peptide and protein hormones modified amino acids or amino acids put together serotonin, melatonin, histamine, epinephrine some glycoproteins Eicosanoids derived from arachidonic acid (fatty acid) prostaglandins or leukotrienes

Hormone Transport in Blood Protein hormones circulate in free form in blood Steroid (lipid) & thyroid hormones must attach to transport proteins synthesized by liver improve transport by making them water-soluble slow loss of hormone by filtration within kidney create reserve of hormone only .1 to 10% of hormone is not bound to transport protein = free fraction

Mechanisms of Hormone Action Response depends on both hormone and target cell Water-soluble hormones bind to receptors on the plasma membrane Activates second messenger system Amplification of original small signal Lipid-soluble hormones bind to receptors inside target cells Responsiveness of target cell depends on Hormone’s concentration Abundance of target cell receptors Influence exerted by other hormones Permissive, synergistic and antagonistic effects Copyright 2009, John Wiley & Sons, Inc.

1 2 4 3 5 1 2 6 4 3 5 1 2 4 3 1 2 3 1 2 1 Water-soluble hormone Receptor cAMP serves as a second messenger to activate protein kinases G protein Protein kinases cAMP Activated protein Protein— Second messenger Activated adenylate cyclase converts ATP to cAMP Activated protein 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 Protein— Second messenger Phosphodiesterase inactivates cAMP Activated adenylate cyclase converts ATP to cAMP Activated protein 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 Water-soluble hormone Receptor cAMP serves as a second messenger to activate protein kinases G protein Protein kinases cAMP Activated protein Second messenger Activated adenylate cyclase converts ATP to cAMP Activated protein 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 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 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 G protein Blood capillary Binding of hormone (first messenger) to its receptor activates G protein, which activates adenylate cyclase Adenylate cyclase Target cell 1

Amplification of Hormone Effects Single molecule of hormone binds to receptor Activates 100 G-proteins Each activates an adenylate cyclase molecule which then produces 1000 cAMP Each cAMP activates a protein kinase, which may act upon 1000’s of substrate molecules One molecule of epinephrine may result in breakdown of millions of glycogen molecules into glucose molecules

Mechanisms of Hormone Action Response depends on both hormone and target cell Water-soluble hormones bind to receptors on the plasma membrane Activates second messenger system Amplification of original small signal Lipid-soluble hormones bind to receptors inside target cells Responsiveness of target cell depends on Hormone’s concentration Abundance of target cell receptors Influence exerted by other hormones Permissive, synergistic and antagonistic effects Copyright 2009, John Wiley & Sons, Inc.

Lipid-soluble hormone diffuses into cell Blood capillary Activated 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 2 3 4 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 DNA Cytosol Target cell Transport protein Free hormone 2 1 Lipid-soluble hormone diffuses into cell Blood capillary Target cell Transport protein Free hormone

General Mechanisms of Hormone Action Hormone binds to cell surface or receptor inside target cell Cell may then synthesize new molecules change permeability of membrane alter rates of reactions Each target cell responds to hormone differently liver cells---insulin stimulates glycogen synthesis adipose---insulin stimulates triglyceride synthesis

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 Responsiveness of target cell depends on Hormone’s concentration Abundance of target cell receptors Influence exerted by other hormones Permissive, synergistic and antagonistic effects Copyright 2009, John Wiley & Sons, Inc.

Hormonal Interactions Permissive effect a second hormone, is needed and strengthens the effects of the first thyroid strengthens epinephrine’s effect upon lipolysis Synergistic effect Two hormones work together to produce a particular result. May be complimentary or as a greater effect estrogen & LH are both needed for oocyte production Antagonistic effects two hormones with opposite effects insulin promotes glycogen formation & glucagon stimulates glycogen breakdown permissive effect. For example, epinephrine alone only weakly stimulates lipolysis (the breakdown of triglycerides), but when small amounts of thyroid hormones (T3 and T4) are present, the same amount of epinephrine stimulates lipolysis much more powerfully. Sometimes the permissive hormone increases the number of receptors for the other hormone, and sometimes it promotes the synthesis of an enzyme required for the expression of the other hormone’s effects. When the effect of two hormones acting together is greater or more extensive than the effect of each hormone acting alone, the two hormones are said to have a synergistic effect. For example, normal development of oocytes in the ovaries requires both follicle-stimulating hormone from the anterior pituitary and estrogens from the ovaries. Neither hormone alone is sufficient. When one hormone opposes the actions of another hormone, the two hormones are said to have antagonistic effects. An example of an antagonistic pair of hormones is insulin, which promotes synthesis of glycogen by liver cells, and glucagon, which stimulates breakdown of glycogen in the liver.

Control of Hormone Secretion Regulated by Signals from nervous system Chemical changes in the blood Other hormones Chronotropic Most hormonal regulation by negative feedback (Few examples of positive feedback) Irregular control will lead to Disorders Copyright 2009, John Wiley & Sons, Inc.

Types of endocrine disorders Hypo-secretion Primary hypo-secretion Deficiency in resources for hormone production Malfunction in hormone producing organ Secondary hypo-secretion Deficiency in tropic “regulatory” hormone Hyper-secretion Hypo-responsiveness Abnormal or deficiency in receptors Lack of activation enzyme Hyper-responsiveness Hormonal upregulation of receptor population (Example) Thyroid hormone to epinephrine receptor