1. The Endocrine System Ebaa M Alzayadneh, DDS, PhD Integrative Physiology and Pharmacology University of Jordan 1

2. Overview of the endocrine system University of Jordan 2

3. Overview of the endocrine system Hormones are chemical messengers that are carried by the bloodstream to different cells in the body. Hormones act at a distance from their place of production directly on the target cell, inciting it to increase or decrease the expression of specific genes. Hormones can be either lipid-based, also known as steroidal, or protein-based, known as non-steroidal. Lipid hormones enter the target cell directly through the cell membrane, and then travel to the nucleus and directly affect expression of target genes. Protein hormones cannot enter the cell, so they bind to receptors on the cell membrane, triggering a secondary messenger system within the cell. University of Jordan 3

4. Overview of the endocrine system Hormone release by the endocrine system is regulated largely through negative feedback loops, and rarely through positive feedback loops. In negative feedback, increases in hormone activity lead to a decrease in the production of that hormone. Endocrine glands in turn have no duct and release their secretions directly into the intercellular fluid or the blood. The main endocrine glands are the pituitary (anterior and posterior lobes), thyroid, parathyroid, adrenal (cortex and medulla), pancreas and gonads. University of Jordan 4

5. Nervous and Endocrine Systems: Act together to coordinate functions of all body systems Nervous systemEndocrine system Responds to stimuli by sending electrical action potentials along neurons using neurotransmitters, the chemical messenger of the nervous system. This response to stimuli is near instantaneous. The nervous system responds rapidly to short-term changes by sending electrical impulses. They may not last for long time (briefer) Specific target Hormones are synthesized at a distance from their target cells, and travel through the bloodstream or intercellular fluid This process takes significantly longer effects are long lasting. Additionally, target cells can respond to minute quantities of hormones and are sensitive to subtle changes in hormone concentration. Broad spectrum of targets 5

6. Endocrine Glands Glands are either: Exocrine – have ducts Endocrine – ductless Secrete hormones into interstitial fluid, diffuse into blood Endocrine glands: Pituitary, thyroid, parathyroid, adrenal and pineal glands Hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, liver, small intestine, skin, heart, adipose tissue, and placenta not exclusively endocrine glands University of Jordan 6

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8. Hormone Activity Hormones affect only specific target tissues with specific receptors Receptors are constantly synthesized and broken down University of Jordan 8

9. Hormones 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 9

10. Chemical classes of hormones Lipid-soluble – use transport proteins Steroid Thyroid Nitric oxide (NO) Water-soluble – circulate in “free” form Amine Peptide/ protein Eicosanoid University of Jordan 10

11. Chemical classes of hormones Lipid-soluble – use transport proteins Steroid Thyroid Nitric oxide (NO) Water-soluble – circulate in “free” form Amine Peptide/ protein Eicosanoid University of Jordan 11

12. Chemical classes of hormones 12 University of Jordan

13. 13 University of Jordan Chemical classes of hormones

14. 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: Permissiveness is the situation in which a hormone cannot exert its full effects without the presence of another hormone. Synergism occurs when two or more hormones produce the same effects in a target cell and their results are amplified. Antagonism occurs when a hormone opposes or reverses the effect of another hormone. University of Jordan 14

15. University of Jordan 15 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 Water-soluble Hormones

16. University of Jordan 16 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 Lipid-soluble Hormones

17. Control of Hormone Secretion Regulated by Signals from nervous system Chemical changes in the blood Other hormones Most hormonal regulation by negative feedback Few examples of positive feedback University of Jordan 17